Browse the corpus

General lnternal Medicine PValues, Type I and Type ll Errors in Clinical Research The Pvalue indicates the likelihood ofthe study result being caused by chance alone. A Pvalue ofless than 0.05 represents a I in 20 chance of obtaining the observed results by chance. A type I error is incorrectly concluding that a statistically significant difference exists between the experimental and control groups. Ifthe study's Pvalue is <0.05, then a <57, chance exists that a type I error has occurred. A type II error is incorrectly concluding no difference exists between the experimental and control groups. Studies with small numbers of subjects may not have the statistical "power" to detect true differences between groups and may be subject to type II errors. DOil'T BE TRICKED . Do not confuse statistical significance with clinical importance; a study that reports statistically significant Pvalues may not be clinically relevant if the effect size is small (absolute difference between outcomes is small). For example, when comparing a new cancer treatment with current therapy, the new treatment may offer a statistically signiflcant increase in survival that translates to a possibly clinically unimportant few weeks (especially if greater morbidity and/or cost is associated with the new treatment). IEST YOURSETF A l9-year-old woman with RLQ abdominal pain and fever has an estimated pretest probability of acute appendicitis of 50'/.. An appendiceal CT scan shows inflammation and a thickened appendiceal wall. This finding is associated with an LR+ of 13.3 for acute appendicitis. What is the posttest likelihood of acute appendicitis? ANSWER: >95'l. (50'2, plus 45% = 95"/,,) . The key to this question is remembering that an LR+ of 10 increases the posttest likelihood of the diagnosis by 45%. The mortaligz rate after cardiogenic shock managed with standard care is 72,2,, but the rate for patients receiving a new medication is 677,. How many patients with cardiogenic shock must be treated with the new medication to save one life? ANSWER: The NNT lslU(o.72 - 0.67)l= 1/0.0s = 20. : I

The mortaligz rate after cardiogenic shock managed with standard care is 72,2,, but the rate for patients receiving a new medication is 677,. How many patients with cardiogenic shock must be treated with the new medication to save one life? ANSWER: The NNT lslU(o.72 - 0.67)l= 1/0.0s = 20. : I Medical Ethics and Professionalism I I I Patient Privacy I l With the advent of the HIPAA regulations, patients must have control over who has access to their personal health information. I The preservation ofconfidentiality is not absolute. Safeguarding the individual or public from harm or honoring the law prevails I over protecting confi dentiality. l l l TEST YOURSELF ') A 78-year old man is admitted with GI bleeding. Colonoscopy reveals metastatic colon cancer. His daughter wishes to know the I results of the colonoscopy. l ANSWER: The information cannot be released unless approved by the patient. l

A 78-year old man is admitted with GI bleeding. Colonoscopy reveals metastatic colon cancer. His daughter wishes to know the I results of the colonoscopy. l ANSWER: The information cannot be released unless approved by the patient. l Advance Planning In advance care planning, the patient articulates and documents his or her values, goals, and preferences for future health care. Advance care planning also includes an advance directive, which contains written instructions for health care used in the event that the patient loses decision making capacity. l I 116 j \ I

t I I t General lnternal Medicine I I I Advance directives include: L . the living will, in which the patient Iists preferences regarding specific treatments and pain control preferences during t terminal illness t o the durable power of attorney for health care, in which the patient designates a surrogate decision maker t o the combined advance directive, which has feafures of both a living will and a health care power of attorney DOil'T BE TRICKED . The surrogate named by the patient in his or her advance directive is the legal decision maker regardless of the surrogate's relationship with the patient. Decision-Making Capacity The physician must assess the patient's decision making abilities to decide whether a surrogate decision maker should be enlisted. To make their own decisions, patients need a set of values and goals, the ability to communicate and understand infor mation, and the ability to reason and deliberate about options. The core components of decisional capacity are: 1. understanding the situation at hand, 2. understanding the risks and benefits of the decision being made, and 3. being able to communicate the decision. DOil'T BE TRICKED . Minors who are not living independently of their parents, not married, or not in the armed forces cannot legally make their own decisions. . Any physician can determine whether a patient has decision-making capacity. Competence is a legal term; only the courts can determine competence. If a patient is incapable of medical decision making, a surrogate decision maker is identified. Without a living will, surrogates can use one of two standards for decision making: . Substituted judgment standard: The surrogate makes the decision that he or she believes the patient would have made. . Best interests standard: The surrogate selects the medical treatment that he or she personally feels is best for the patient. TESTYOURSEIF An 82-year-old woman is hospitalized for the fourth time in 12 months. She lives alone and is unable to take her medications prop- erly. She cannot articulate a plan to manage her disease. AI\ISWER: Seek appointment of a guardianship, because the patient cannot describe realistic plans for living at home alone.

TESTYOURSEIF An 82-year-old woman is hospitalized for the fourth time in 12 months. She lives alone and is unable to take her medications prop- erly. She cannot articulate a plan to manage her disease. AI\ISWER: Seek appointment of a guardianship, because the patient cannot describe realistic plans for living at home alone. Withholding or Withdrawing Treatment Withdrawing treatment is reasonable if, from the patient's perspective, the expected beneflts of treatment no longer outweigh its burdens. Patients who have do-not resuscitate orders are still eligible to receive other therapeutic life-prolonging or palliative I I measures. I t Physicians are not obligated to administer interventions that are physiologically futile. Physicians may also disagree with a patient's legitimate choice of care if it violates their ethical principles. If consensus about treatment cannot be reached, options t include transfer of the patient to another physician and review by a hospital ethics committee. I Administration of nutrients and fluids by artificial means is a life-prolonging measure, guided by the same principles for deci- I I sion making that are applied to other treatments. I L I L I I I 117 I L i

General lnternal Medicine Treatment Treatment varies according to cause ofvertigo. r Canalith repositioning with the Epley maneuver is the treatment of choice for BPPV . Vestibular rehabilitation and/or diuretics are the treatment of choice for Meniere disease. o Short term use of vestibular suppressants (antihistamines, benzodiazepines, and antiemetics) can provide temporary relief of other causes of vertigo. o Vestibular and balance rehabilitation therapy (VBRT) is effective in the treatment of various forms of dizziness (vertigo, disequilibrium, and nonspecific dizziness). DOil'T BE TRTSKED . Advanced imaging is not needed for BPPV confirmed by physical examination. Systemic Exertion lntolerance Disease Diagnosis Systemic exertion intolerance disease (SEID) is defined as unexplained fatigue lasting more than 6 consecutive months that impairs the ability to perform desired activities. Other diagnostic criteria include postexertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance (symptoms worse in upright position). Extensive diagnostic evaluation is not needed in patients with typical symptoms and with normal physical examination and basic laboratory study results. Treatment Establishing goals of therapy and managing patient expectations are key treatment components of SEID. Patients with SEID benefit most from a structured, multimodal approach that includes regularly scheduled office visits, CBT, and graded exercise therapy. No speciflc class of medication has been shown to be effective in SEID. DON'T BE TRICKED . Do not obtain viral titers to evaluate SEID. lnsomnia Diagnosis Insomnia includes problems of sleep initiation, sleep maintenance, early morning waking, or nonrestorative and poor-quality sleep. Insomnia may be associated with shift work, obesit5r, sleep apnea, and restless legs slmdrome. Obtain polysomnography only for suspected sleep apnea or periodic limb movement disorder. 120

General lnternal Medicine STUDY TABLE: Differential Diagnosis of Daytime Sleepiness Condition Characteristics Restless legs syndrome An uncomfortable or restless feeling in the legs most prominent at night and at rest, associated with an urge to move and alleviated by movement Look for iron deficiency Associated with periodic limb movement disorder in most patients Periodic limb movement disorder Repetitive stereotypic leg movement during sleep and during quiet wakefulness. Movement may range from extension of the great toe to triple flexion of the entire leg. Central sleep apnea syndrome Repetitive pauses in breathing during sleep without upper airway occlusion Associated history of HF or CNS disease Obstructive sleep apnea syndrome Upper airway obstruction during inspiration in sleep History of snoring, witnessed pauses in respiration, large shirt collar size, and daytime sleepiness Shift-work sleep disorder History of insomnia associated with shift work (e.9., permanent night shifts) Sleep deprivation Six hours or less of sleep is associated with daytime sleepiness and performance deficits Narcolepsy Daytime sleepiness with cataplexy, hypnagogic hallucinations, and sleep paralysis frequently coexisting with other sleep disorders Treatment First line treatment is always nondrug. Nondrug treatment of insomnia includes:

STUDY TABLE: Differential Diagnosis of Daytime Sleepiness Condition Characteristics Restless legs syndrome An uncomfortable or restless feeling in the legs most prominent at night and at rest, associated with an urge to move and alleviated by movement Look for iron deficiency Associated with periodic limb movement disorder in most patients Periodic limb movement disorder Repetitive stereotypic leg movement during sleep and during quiet wakefulness. Movement may range from extension of the great toe to triple flexion of the entire leg. Central sleep apnea syndrome Repetitive pauses in breathing during sleep without upper airway occlusion Associated history of HF or CNS disease Obstructive sleep apnea syndrome Upper airway obstruction during inspiration in sleep History of snoring, witnessed pauses in respiration, large shirt collar size, and daytime sleepiness Shift-work sleep disorder History of insomnia associated with shift work (e.9., permanent night shifts) Sleep deprivation Six hours or less of sleep is associated with daytime sleepiness and performance deficits Narcolepsy Daytime sleepiness with cataplexy, hypnagogic hallucinations, and sleep paralysis frequently coexisting with other sleep disorders Treatment First line treatment is always nondrug. Nondrug treatment of insomnia includes: o CBT for insomnia (first-line therapy), a multicomponent treatment that includes cognitive therapy (addresses maladaptive beliefs and expectations about sleep), educational interventions (sleep hygiene), and behavioral interventions (sleep restriction therapy, stimulus-control therapy, relaxation techniques) . avoiding caffeine, nicotine, alcohol, and electronic devices before sleep Pharmacologic therapy is second line treatment fbr insomnia. Nonbenzodiazepine drugs (zolpidem, zaleplon, eszopiclone) are preferred to benzodiazepines; sedation, disorientation, and agitation, as well as (rarely) sleep driving, sleep walking, and sleep eating, may occur.

o CBT for insomnia (first-line therapy), a multicomponent treatment that includes cognitive therapy (addresses maladaptive beliefs and expectations about sleep), educational interventions (sleep hygiene), and behavioral interventions (sleep restriction therapy, stimulus-control therapy, relaxation techniques) . avoiding caffeine, nicotine, alcohol, and electronic devices before sleep Pharmacologic therapy is second line treatment fbr insomnia. Nonbenzodiazepine drugs (zolpidem, zaleplon, eszopiclone) are preferred to benzodiazepines; sedation, disorientation, and agitation, as well as (rarely) sleep driving, sleep walking, and sleep eating, may occur. Restless legs syndrome is treated with dopaminergic agents (pramipexole or ropinirole) or with levodopa carbidopa. Prescribe supplemental iron for patients with restless legs syndrome when the serum ferritin level is <75 ng/ml. DON'T BE TRICKED . Do not select antidepressants for insomnia unless the patient is depressed. . Do not select an antihistamine for insomnia. Ch ronic Venous I nsufficiency Diagnosis Characteristic symptoms and findings of chronic venous insufficiency or associated complications include: r leg heaviness, tiredness . dependent Ieg edema o hyperpigmentation, especially at medial ankle r pruritus and eczema o varicose or reticular veins . venous ulceration 121

I I I General lnternal Medicine Multimodal therapy is typically superior to single-modality therapy. Drug treatment for neuropathic pain includes: . capsaicin cream or a lidocaine patch or cream o gabapentin and pregabalin . tricyclic antidepressants o SNRIs (duloxetine and venlafaxine) Initial drug therapy for nociceptive pain is primarily NSAIDs (if an inflammatory component is present) No evidence supports the efficacy of long-term opioids in managing chronic noncancer pain. Despite the lack of evidence fbr their efficacy, if opioids are used, the following should be done: . an assessment to evaluate for risk of abuse and diversion . written treatment agreements . adherence monitoring (urine drug screens) . surveillance using prescription monitoring programs DON'T BE TRICKED . Do not concurrently prescribe opioids and benzodiazepines. Palliative Care Palliative care may be provided concurrently with life-prolonging therapies or with therapies with curative intent. Hospice, on the other hand, is a specialized type of palliative care that is reserved for patients in the terminal phase of their disease, arbitrar- ily defined as the last 6 months of life. Acute and Chronic Pain at the End of Life Pharmacologic management of pain progresses in a stepwise fashion.

Palliative Care Palliative care may be provided concurrently with life-prolonging therapies or with therapies with curative intent. Hospice, on the other hand, is a specialized type of palliative care that is reserved for patients in the terminal phase of their disease, arbitrar- ily defined as the last 6 months of life. Acute and Chronic Pain at the End of Life Pharmacologic management of pain progresses in a stepwise fashion. . Use acetaminophen, aspirin, or NSAIDs for rnild to moderate pain. . If pain persists or increases, add a low-dose or low-potency opioid (e.g., oxycodone). Avoid codeine and tramadol. . Increase opioid potency (e.g., morphine) or add higher doses fbr persistent or moderate to severe pain at onset. . Add adjuvant agents (tricyclic antidepressants, gabapentinoids, or carbamazepine) at any step. . Prescribe around-the-clock analgesics for persistent, chronic pain rather than as needed. Sf UDY TABLE: Opioids Commonly Used in Palliative Care Opioid Comments Hydrocodone Variable efficacy lncreased time to analgesic onset in liver failure Hydromorphone Better choice if kidney disease is present Reduce dose and frequency in liver failure/cirrhosis Methadone Low cost, long acting, available as liquid Long but variable half-life, which contributes to the risk for accumulation and toxicity during initiation Oxycodone lncreased half-life and variable onset in liverfailure; if used, reduce dose and frequency Morphine Avoid in liver failure/cirrhosis, kidney injury Fentanyl Safest long-acting drug in kidney and liver failure Start lower dose patch in liverfailure 124

General lnternal Medicine Opioids do not have an analgesic efficacy ceiling and can be titrated upward as needed until limiting adverse effects appear. Combination opioid-acetaminophen limits the dose range because of potential acetaminophen toxiciff. Common adverse effects of opioids include constipation, sedation, nausea, and itching (not from an allerry). In patients using short acting opioids who require longer lasting relief, long-acting agents are appropriate; however, long-acting opioids should not be the initial opioid prescribed in opioid naive patients. Warnings about opioid use: o Fentanyl should be used only in opioid tolerant patients. o Meperidine is not recommended for pain because of an increased risk for seizure. o Tramadol has significant drug interactions, especially with other serotonergic medications. r Methadone should be initiated and titrated only by experts. In the administration of opioids, oral routes are preferred (do not use IM). . Sublingual or subcutaneous routes may be used for patients unable to use an oral route. Neuropathic pain is characterized by burning, tingling, or lancinating pain. Add tricyclic antidepressants, SNRIs (venlafaxine, duloxetine), or antiepileptic medications (gabapentin, pregabalin, carbamazepine) to the pain regimen. Treat bone pain with anti-inflammatory medications (NSAlDs or glucocorticoids) or bisphosphonates (pamidronate, zoledronate). All patients receiving scheduled opioids should be taking a scheduled bowel regimen b prevent constipation, in this order:

. Sublingual or subcutaneous routes may be used for patients unable to use an oral route. Neuropathic pain is characterized by burning, tingling, or lancinating pain. Add tricyclic antidepressants, SNRIs (venlafaxine, duloxetine), or antiepileptic medications (gabapentin, pregabalin, carbamazepine) to the pain regimen. Treat bone pain with anti-inflammatory medications (NSAlDs or glucocorticoids) or bisphosphonates (pamidronate, zoledronate). All patients receiving scheduled opioids should be taking a scheduled bowel regimen b prevent constipation, in this order: o stimulant laxative with or without docusate . osmotic agent (PEG, sorbitol, or lactulose) . naldemedine, naloxegol, ormethylnaltrexone gTUDY TABLE: Treatment of Nausea in Palliative Care Cause of Nausea Mediating Receptor Pathway Treatment Gut wall stretching or dilatation Dopamine type 2 (D2) receptors in the Gl Antidopaminergic antiemetics (constipation, bowel obstruction, ileus) tract (metoclopramide, prochlorperazine, haloperidol, olanzapine) Gut mucosal injury (radiation, Serotonin (5-hydroxytryptamine-3 [5-HT3]) Serotonin antagonists (ondansetron, chemotherapy, infection, inflammation, receptors in the Gl tract granisetron) direct tumor invasion) Drugs, metabolic by-produas, bacterial D2 receptors, 5-HT3 receptors, and Antidopaminergic antiemetics, toxins neurokinin type 1 receptors in the glucocorticoids, serotonin antagonists, and chemoreceptor trigger zone neurokinin-1 receptor blockers (aprepitant, netupitant) Motion sickness, labyrinthine disorders Histaminetype 1 (H,)receptors and Anticholinergic antiemetics (scopolamine, muscarinic acetylcholine receptors in the diphenhydramine, promethazine) vestibular system Anticipatory nausea Unknown, presumed cerebral cortex Behavioral therapy, benzodiazepines, olanzapine lncreased intracranial pressure Unknown Glucocorticoids

o stimulant laxative with or without docusate . osmotic agent (PEG, sorbitol, or lactulose) . naldemedine, naloxegol, ormethylnaltrexone gTUDY TABLE: Treatment of Nausea in Palliative Care Cause of Nausea Mediating Receptor Pathway Treatment Gut wall stretching or dilatation Dopamine type 2 (D2) receptors in the Gl Antidopaminergic antiemetics (constipation, bowel obstruction, ileus) tract (metoclopramide, prochlorperazine, haloperidol, olanzapine) Gut mucosal injury (radiation, Serotonin (5-hydroxytryptamine-3 [5-HT3]) Serotonin antagonists (ondansetron, chemotherapy, infection, inflammation, receptors in the Gl tract granisetron) direct tumor invasion) Drugs, metabolic by-produas, bacterial D2 receptors, 5-HT3 receptors, and Antidopaminergic antiemetics, toxins neurokinin type 1 receptors in the glucocorticoids, serotonin antagonists, and chemoreceptor trigger zone neurokinin-1 receptor blockers (aprepitant, netupitant) Motion sickness, labyrinthine disorders Histaminetype 1 (H,)receptors and Anticholinergic antiemetics (scopolamine, muscarinic acetylcholine receptors in the diphenhydramine, promethazine) vestibular system Anticipatory nausea Unknown, presumed cerebral cortex Behavioral therapy, benzodiazepines, olanzapine lncreased intracranial pressure Unknown Glucocorticoids Dyspnea Treat reversible causes ofdyspnea, such as pleural effusions, infection, and anemia. Systemic opioids are the standard ofcare for refractory dyspnea in advanced disease.

o stimulant laxative with or without docusate . osmotic agent (PEG, sorbitol, or lactulose) . naldemedine, naloxegol, ormethylnaltrexone gTUDY TABLE: Treatment of Nausea in Palliative Care Cause of Nausea Mediating Receptor Pathway Treatment Gut wall stretching or dilatation Dopamine type 2 (D2) receptors in the Gl Antidopaminergic antiemetics (constipation, bowel obstruction, ileus) tract (metoclopramide, prochlorperazine, haloperidol, olanzapine) Gut mucosal injury (radiation, Serotonin (5-hydroxytryptamine-3 [5-HT3]) Serotonin antagonists (ondansetron, chemotherapy, infection, inflammation, receptors in the Gl tract granisetron) direct tumor invasion) Drugs, metabolic by-produas, bacterial D2 receptors, 5-HT3 receptors, and Antidopaminergic antiemetics, toxins neurokinin type 1 receptors in the glucocorticoids, serotonin antagonists, and chemoreceptor trigger zone neurokinin-1 receptor blockers (aprepitant, netupitant) Motion sickness, labyrinthine disorders Histaminetype 1 (H,)receptors and Anticholinergic antiemetics (scopolamine, muscarinic acetylcholine receptors in the diphenhydramine, promethazine) vestibular system Anticipatory nausea Unknown, presumed cerebral cortex Behavioral therapy, benzodiazepines, olanzapine lncreased intracranial pressure Unknown Glucocorticoids Dyspnea Treat reversible causes ofdyspnea, such as pleural effusions, infection, and anemia. Systemic opioids are the standard ofcare for refractory dyspnea in advanced disease. DO['T BE TRICKED o Oxygen supplementation is helpful if the patient is hypoxic but is otherwise inelTective. . Fans are elTective in reducing dyspnea in nonhypoxic patients.

Dyspnea Treat reversible causes ofdyspnea, such as pleural effusions, infection, and anemia. Systemic opioids are the standard ofcare for refractory dyspnea in advanced disease. DO['T BE TRICKED o Oxygen supplementation is helpful if the patient is hypoxic but is otherwise inelTective. . Fans are elTective in reducing dyspnea in nonhypoxic patients. 125

General lnternal Medicine . decreased deep tendon reflexes o diminished strength in the affected extremity Cervical myelopathy causes neck pain that may include: . upper motor neuron signs (increased muscle tone, hyperreflexia, and clonus) in the lower extremities . numbness or paresthesias in the arms . lower motor signs (weakness, diminished reflexes) in the upper extremities ln the absence of red flags, imaging is not necessary fbr mild pain that does not interfere with activities of daily living. MRI is recommended when myelopathy is suspected or fbr symptoms failing to respond to conservative therapy. A multimodal treatment approach may include physical therapy, ice or heat applications, and NSAlDs. Muscle relaxants are effective for acute neck pain associated with muscle spasm. Surgery is reserved for patients with confirmed cervical nerve root compression and either progressive motor weakness or persistent radicular pain for more than 6 12 weeks. DO]|'T BE TRICKED . Regular use of a cervical collar should be discouraged because it may delay improvement. Knee The most common cause of knee pain in patients aged <45 years, especially women, is the patellofemoral pain syndrome. The pain is peripatellar and exacerbated by overuse (running), by descending stairs, or af'ter prolonged sitting. Diagnosis is con firmed by firmly compressing the patella against the femur and moving it up and down along the groove of the fbmur, reproduc ing pain. The condition is self-limited. Minimizing high-impact activity, performing quadriceps strengthening exercises, icing, and NSAID treatment improve symptoms. Prepatellar bursitis is associated with anterior knee pain and swelling anterior to the patella. When acute, suspect infection chronic symptoms are often caused by trauma or repetitive kneeling. Perfbrm a bursa aspiration to rule out inf'ection. Anserine bursitis can cause knee pain that is worse with activity and at night. The anserine bursa is located medially about 6 cm below the joint line. Anserine bursitis is common in patients with OA. In general, bursitis treatment includes rest, ice, and NSAIDS. Iliotibial band syndrome is a common cause of knife like lateral knee pain that occurs with vigorous flexir-rn extension activi ties ofthe knee (running). Treat with rest and stretching exercises.

Anserine bursitis can cause knee pain that is worse with activity and at night. The anserine bursa is located medially about 6 cm below the joint line. Anserine bursitis is common in patients with OA. In general, bursitis treatment includes rest, ice, and NSAIDS. Iliotibial band syndrome is a common cause of knife like lateral knee pain that occurs with vigorous flexir-rn extension activi ties ofthe knee (running). Treat with rest and stretching exercises. Trauma may result in a ligament tear, which produces a noticeable "popping" sensation at the time of injury in 50'1, of patients. Typically, a large efl'usion collects rapidly. Check for stability of major ligaments by stressing the ligament; normal knees will have minimal give. Most MCL and PCL tears can be managed conservatively. ACL tears frequently require surgical reconstruc tion, especially in active patients or those with an unstable knee. Meniscal tears present with pain, locking, catching, and grinding. Tenderness usually localizes to the joint line on the affected side and with tibial rotation as the leg is extended. Surgery for acute meniscal tears is reserved for mechanical symptoms that persist beyond 4 weeks. MRI is reserved for patients in whom surgery is being considered and in patients with persistent lock ing and catching despite appropriate initial management. Initial management of both acute and chronic meniscal tears consists of rest, ice, and muscle strengthening. For OA related meniscal tear, physical therapy is as eflective as partial meniscectomy in relieving pain. Hip Most patients with chronic hip pain have degenerative arthritis associated with other large joint arthritis symptoms. Pain or restricted range of motion with the FADIR (Flexion, ADduction, and Internal Rotation) test suggests intra articular disease. 128

General lnternal Medicine Look for greater trochanter pain syndrome, characterized by lateral point tenderness and full range ofmotion except for painful resisted abduction. Manage with acetaminophen or NSAIDs. Glucocorticoid injection can be considered for persistent symptoms. Risk factors for osteonecrosis include alcoholism, sickle cell disease, SLE, and prolonged glucocorticoid use. Diagnose early osteonecrosis with hip MRI. Advanced disease will show flattening of the femoral head on x ray. Treatment of osteonecrosis is often hip replacement for recalcitrant pain and disability. Consider bone metastases to the hip in patients with a history of cancer DOil'T BE TRICKED . True hip joint pain usually presents as groin pain Ankle For a ligament tear, look for ecchymoses around the joint, suggesting bleeding in the region of the torn ligament, and any swell ing or obvious deformity. Treatment of acute ankle sprain includes ice, ankle immobilization followed by early remobilization with weight bearing as tolerated, and oral or topical NSAIDs. Look for Achilles tendon rupture (a snapping sound followed by posterior ankle pain and inability to plantarflex). Rarely, this may occur in older men who are taking a fluoroquinolone antibiotic. DOil'T BE TRICKED . Select ankle x ray following ankle sprain only if the patient cannot bear weight or if bone pain is localized to the lateral or medial malleolus, base of the fifth metatarsal, or navicular bone. Foot Plantar fasciitis, the most common cause of inferior heel pain, is characterized by pain that worsens with walking, especially with the first steps in the morning or after resting, in addition to localized tenderness along the plantar fascia or the calcaneal insertion site. ]\ifanage with weight loss, rest, and calf/heel stretching. NSAIDs can be added. Symptoms of Morton neuroma include pain, numbness, and tingling in the forefoot, usually between the third and fourth toes, aggravated by walking on hard surfaces and wearing tight or high-heeled shoes. Compressing the forefoot or space bet'rveen the third and fourth toes reproduces the symptoms. Initial therapy includes wearing wider shoes and arch support. DON'T BE TRICKED . Do not order heel radiography for plantar fasciitis.

Symptoms of Morton neuroma include pain, numbness, and tingling in the forefoot, usually between the third and fourth toes, aggravated by walking on hard surfaces and wearing tight or high-heeled shoes. Compressing the forefoot or space bet'rveen the third and fourth toes reproduces the symptoms. Initial therapy includes wearing wider shoes and arch support. DON'T BE TRICKED . Do not order heel radiography for plantar fasciitis. Hand De Quervain tenosynovitis is typically seen in young women with pain on the radial side of the wrist during pinch grasping or thumb and wrist movement. The diagnosis is established with a positive Finkelstein test. Initial management includes rest, NSAIDs, and splinting; glucocorticoid injections provide sympto matic relief if conservative therapy is ineffective. Consider carpal tunnel syndrome for pain and paresthesias, particular$ at night, localized to the thumb, flrst two fingers, and radial half of the ring finger. Splinting at night is first line tinkelstein fest: Finkelstein test for de ouervain stenosing tenosynovitis. Pain therapy for carpal tunnel syndrome. Glucocorticoid injection or el icited by flexing the th u m b i nto the pal m, closing the fi ngers over the thu mb, and a short course of oral glucocorticoids may provide sl,rnptomatic then bending the wrist in the ulnar direction is confirmatory. 129

General lnternal Medicine improvement. Carpal tunnel release surgery is indicated for severe carpal tunnel syndrome (muscle weakness or EMG evidence of nerve injury). Shoulder Rotator cuffdisease refers to all symptomatic rotator cuff disorders, which typically occur with: . rotator cuff tendinitis (pain without weakness) . rotator cuff tears (pain with weakness) r subacromial bursitis (pain located 10 cm down the outer upper arm, especially at night) . impingement syndrome (impingement of the shoulder tendons or bursa by the shoulder bones presenting with lateral deltoid pain that is aggravated by reaching) Rotator cuff disease is the most common cause of shoulder pain. Pain from rotator cuff disease is localized to the upper arm near the deltoid insertion and is worsened with overhead activities and when lying on the affected side. Consider other causes of shoulder pain. Adhesive capsulitis (frozen shoulder) presents with an impingement pain pattern accompanied by stiffness and loss of active and passive external rotation or abduction. Acromioclavicular joint pain is localized to the distal end of the clavicle and is most pronounced when the patient reaches across their body to the opposite shoulder. Glenohumeral joint pain is aggravated by any shoulder movement. Biceps tendinitis pain is aggravated by lifting and wrist supination. Biceps tendon rupture is often associated with a traumatic event but may be spontaneous and presents with a visible or palpable mass near the elbow or mid arm ("Popeye sign") and ecchymosis. Testing MRI is the best imaging modality for acute complete rotator cuff tears, although ultrasonography is more cost effective. Treatment Conservative therapy is indicated for patients with suspected rota- tor cuff tendinitis, incomplete tears, and subacromial bursitis. NSAIDs and exercises that strengthen the rotator cuff muscles and improve flexibility are effective in improving pain. Immediate surgery is indicated for an acute full-thickness tear or chronic tears that fail to respond to conservative therapy over several months. Biteps Tendon Rupture: Biceps tendon rupture showing a visible mas ("Popeye DOll'T BE TRICKED sign") at the mid arm with associated ecchymoses.

Immediate surgery is indicated for an acute full-thickness tear or chronic tears that fail to respond to conservative therapy over several months. Biteps Tendon Rupture: Biceps tendon rupture showing a visible mas ("Popeye DOll'T BE TRICKED sign") at the mid arm with associated ecchymoses. o Do not immobilize rotator cuffinjuries in a sling. o Constant shoulder pain with normal shoulder examination suggests referred pain (e.g., Pancoast tumor) or neuropathic pain (e.g., cervical spine radiculopathy). t 130

General lnternal Medicine In patients with persistently elevated triglyceride levels despite statin therapy who have ASCVD or diabetes and several other risk factors, the addition of icosapent ethyl may decrease the risk for cardiovascular events. Fibrates are indicated in patients with severe hypertriglyceridemia (>500 mg/dl) to prevent acute pancreatitis. a Dep ressron Screening Routine screening is recommended for all adults, including postpartum women and older adults, using the two question model: . "Over the past 2 weeks, have you felt down, depressed, or hopeless?" o "Over the past 2 weeks, have you felt little interest or pleasure in doing things?" Ifscreening is positive, further evaluation for depression is warranted. Diagnosis Major depressive disorder is diagnosed when at least five of the following symptoms are consistently present during the same 2 week period, at least one of which is depressed mood or Ioss of interest or pleasure' . depressed mood . Ioss ofinterest in daily activities . weight loss or gain o insomnia or hypersomnia o psychomotor agitation or retardation r fatigue o feelings of worthlessness or guilt o diminished ability to concentrate . recurrent thoughts of death or suicide Refer patients with a suicide plan or psychotic features to a psychiatrist, and hospitalize any patient (even against the patient's wishes) who is in imminent danger of harming himself or herself or others. DO['T BETRICKED o Select bipolar disorder if depression is accompanied by previous or current manic symptoms. Mimics of major depressive disorder: . Adjustment reaction with depressed mood: depression with a clear precipitant. Usually resolves without medication : :

DO['T BETRICKED o Select bipolar disorder if depression is accompanied by previous or current manic symptoms. Mimics of major depressive disorder: . Adjustment reaction with depressed mood: depression with a clear precipitant. Usually resolves without medication : : following resolution of the acute stressor. . Bipolar disorder: one or more manic or mixed manic and depressive episodes, usually accompanied by major depressive disorder. r Seasonal affective disorder: a subtype of major depression, with onset during fall or winter and seasonal remission. Responds to phototherapy and SSRIs. o Grief reaction: transient major depression may be present, but sadness without complete depression is more common. Pervasive and generalized guilt and persistent vegetative signs and symptoms are not consistent with normal grief. Loss of self esteem is a symptom of depression rather than grief. 132

General lnternal Medicine o PMDD: characterized by the cyclical recurrence of >S symptoms oldepression, anxiery and emotional labilisz having their onset within 1 week beflore menstruation and resolution within 1 week after menstruation. o Medical conditions: consider substance use disorders, hypothyroidism, Cushing syndrome, Parkinson disease, and med- ications (interferon, glucocorticoids). Routine laboratory testing for these conditions is not warranted unless suggested by history and physical examination findings. Treatment For initial acute therapy, select either CBT or second-generation antidepressants. Guide selection ofan antidepressant by differ- ences in side effect profiles and personal or family history of response to a specific agent. Commonly tested treatment principles include: o Sertraline is safe for patients with cardiovascular disease. . Bupropion has fewer effects on sexual function and weight gain. o Mirtazapine causes sedation and weight gain (useful for patients with insomnia or weight loss). . Paroxetine is classified as pregnancy category D (do not use). It has the highest rate of sexual dysfunction among SSRIs, a higher rate ofweight gain, and the highest rate ofdiscontinuation syndrome (dizziness, fatigue, headache, and nausea). For patients in whom treatment with a single SSRI is unsuccessful, response to a medication change does not depend on whether patients receive a different SSRI, a non-SSRI antidepressant, a combination of two antidepressants, augmentation with lithium, or cognitive therapy. Therefore, in nonresponding patients, modiff treatment (increase dose, switch, or add another drug) if the patient does not have >507, reduction in symptom score with pharmacotherapy within several weeks.

For patients in whom treatment with a single SSRI is unsuccessful, response to a medication change does not depend on whether patients receive a different SSRI, a non-SSRI antidepressant, a combination of two antidepressants, augmentation with lithium, or cognitive therapy. Therefore, in nonresponding patients, modiff treatment (increase dose, switch, or add another drug) if the patient does not have >507, reduction in symptom score with pharmacotherapy within several weeks. STUDY ?ABtf : Managing Duration of AntidepressantTherapy lndications Therapy First episode of depression lnitiate treatment and continue at the dosage required to achieve remission for an additional 4-9 months. First recurrence of depression lncrease maintenance treatment duration to one to two times the inter-episode interval (forexample, choose 18-36 months if the second episode occurs 1 8 months after the first episode). Three or more recurrences of depression, recurrence within Select long-term maintenance therapy 1 year of successful treatment, or suicide attempt Be alert for serotonin syndrome in patients taking SSRIs, particularly with concurrent use of other SSRIs, MAOIs, St. John's wort, trazodone, dextromethorphan, linezolid, tramadol, or buspirone. Mild symptoms include nausea, vomiting, flushing, and diaphoresis. Severe symptoms include hyperreflexia, myoclonus, muscular rigidity, and hyperthermia. DOil'T BE TRICKED . Always ask about episodes of mania or hypomania before starting antidepressant therapy, because unipolar depression treatments may provoke mania. . Antidepressant drugs should not be stopped abruptly. . Bereavement does not usually require pharmacologic treatment. Bipolar Disorder Diagnosis Bipolar disorder features episodes of depression as well as periods of mania or hypomania. Manic findings include elevated, expansive, or irritable mood; hypersexuality; spending sprees; grandiosity; decreased need for sleep; and disruption ofsocial or occupational lu ncl ioning. 133

General lnternal Medicine Smoking Cessation Smoking cessation reduces all cause mortality by up to 50%; when it appears as a potential answer to a test question, it is almost always the correct choice. Treatment The Five A s and the 5 R's are tvvo motivational interviewing techniques to use when counseling for behavior change, including smoking cessation, at risk drinking, and other substance use. STUDY TABLE: Behavioral lnterventions FiveAs Five R's Ask about tobacco use. Encourage patient to think of Relevance of quitting smoking to their lives. Advise to quit. Assist patient in identifying the Risks of smoking. Assess willingness to quit. Assist the patient in identifying the Rewards of smoking cessation. Assist in attemptto quit. Discuss with the patient Roadblocks or barriers to attempting cessation. Arrange follow-up. Repeat the motivational intervention at all visits. STUDY TABLE: Pharmacologic Treatments for Smoking Cessation Agent Notes Long-acting nicotine patch and lncreases smoking cessation 1.5 times more than control. Caution with recent Ml, anhythmia, and short-acting nicotine gum, nasal unstable angina. spray, inhaler, lozenges Bupropion lncreases smoking cessation rates about 2 times more than control. Avoid with seizure disorder and eating disorder. May be associated with suicidal ideation. Safety in pregnancy is unclear. Varenicline lncreases smoking cessation rates about 3.5 times more than control and almost 2 times more than bupropion; more effective than nicotine replacement monotherapy Combination therapy is more effective than monotherapy. r Behavioral intervention and pharmacotherapy are more effective than either therapy used alone. . Bupropion and varenicline can be used with long-acting (nicotine patches) or short-acting (nicotine gum, lozenges, inhal ers, nasal spray) nicotine replacement. o Combination nicotine replacement therapy (long and short acting nicotine replacement) is more effective than nicotine monotherapy.

r Behavioral intervention and pharmacotherapy are more effective than either therapy used alone. . Bupropion and varenicline can be used with long-acting (nicotine patches) or short-acting (nicotine gum, lozenges, inhal ers, nasal spray) nicotine replacement. o Combination nicotine replacement therapy (long and short acting nicotine replacement) is more effective than nicotine monotherapy. DOT{'T BE TRICKED . Nicotine replacement therapy is not contraindicated following MI and can be started in the hospital. o SSRIs show no significant benefit for smoking cessation. . E-cigarettes are not approved by the FDA for smoking cessation. Alcohol Use Disorder Screening Ask all patients about their level of alcohol consumption and follow up with screening tests for patients with "at risk drinking." Patients with AUDIT C scores >4 for men and >3 for women or a CAGE questionnaire score >1 are candidates for further evalu ation and intervention. 135

General lnternal Medicine DOI{'T BE TRICKED . Give thiamine replacement before administering glucose. . Do not prescribe antipsychotic medications, because these agents lower the seizure threshold. o No evidence supports that continuous infusion therapy with short-acting benzodiazepines provides better outcomes than oral therapy for acute alcohol withdrawal. . Not all heavy drinkers who stop abruptly experience withdrawal, and treatment with benzodiazepines is not always needed. TESTYOURSELF A 36-year old man with a history olheavy alcohol use is evaluated within 24 hours of his last drink. BP is 172,98mm Hg, and pulse rate is 120/min. He is tremulous and having visual hallucinations. ANSWER: For diagnosis, choose alcohol withdrawal syndrome. For management, select hospitalization and treatment with symptom trigEered benzodiazepines. Opioid Use Disorder Prescription opioids are a major cause of morbidity and mortality. The risk for overdose is increased with higher doses (>50 morphine mg equivalents/d) and concurrent benzodiazepine prescription. Treatment Most patients with opioid use disorder will require psychosocial support and medication-assisted treatment (buprenorphine- naloxone, buprenorphine, IM naltrexone). Intranasal naloxone is an important adjunctive therapy in opioid use disorder. Friends and family members may also receive prescriptions and training in naloxone use. Somatic Symptom and Related Disorders Diagnosis Diagnostic criteria for somatic symptom disorder are as follows: . at least one somatic symptom causing distress or interference with daily life r excessive thoughts, behaviors, and feelings related to the somatic symptom(s) r persistent somatic symptoms for at least 6 months Patients attribute their symptoms to an undiagnosed disorder despite several negative evaluations and are often not reassured despite repeated evaluations. Treatment The principles of therapy include regular office appointments with one physician. The patient should be reassured that life- threatening conditions have been ruled out and should be given a plausible explanation for the symptoms. Among all treat ments, CBT has the broadest evidence ofbenefit.

. at least one somatic symptom causing distress or interference with daily life r excessive thoughts, behaviors, and feelings related to the somatic symptom(s) r persistent somatic symptoms for at least 6 months Patients attribute their symptoms to an undiagnosed disorder despite several negative evaluations and are often not reassured despite repeated evaluations. Treatment The principles of therapy include regular office appointments with one physician. The patient should be reassured that life- threatening conditions have been ruled out and should be given a plausible explanation for the symptoms. Among all treat ments, CBT has the broadest evidence ofbenefit. DOT{'T BE TRICKED . Choose conversion disorder if a patient has abnormal sensation or motor function (such as limb weakness) that is not explained by a medical condition and is inconsistent with physical examination findings. . Choose illness anxiety disorder (previously hypochondriasis) ifthe patient has excessive worry about general health and preoccupation with health-related activities but has no or only minor symptoms. 138

General lnternal Medicine o disorganized speech, such as frequent derailment or incoherence . grossly disorganized or catatonic behavior . negative symptoms, such as affective flattening, alogia (concrete replies to questions and restricted spontaneous speech), or avolition (inability to initiate and persist in goal-directed activities) Treatment Begin a second-generation antipsychotic agent (olanzapine, risperidone, quetiapine, aripiprazole), and refer patients to a psychiatrist. Attentio n- Deficit/Hype ra ctivity D iso rd e r Diagnosis ADHD usually first manifests in childhood and is characterized by inattention, hyperactivity, and impulsivity with functional impairment in at least tlvo settings (home, work, school). ADHD is more prevalent in patients with mood disorders and sub- stance use disorder. Treatment Treat ADHD with stimulants (e.9., amphetamine or methylphenidate), but beware of the potential for abuse and use with cau tion in patients with hypertension or cardiovascular disease. Atomoxetine is an SNRI approved for treatment of ADHD in adults. CBT may be beneficial alone or used as an adjunctive therapy. Falls Diagnosis Patients with a history of one fall in the past year or those who feel unsteady or unbalanced should be evaluated for balance or gait disturbance with a Timed Up and Go test. A time of longer than 12 seconds is abnormal, and the patient should be referred for full fall evaluation. Medications associated with fall risk (psychotropics, sedative/hypnotics) should be removed if possible. Do not discontinue or avoid starting anticoagulation in patients with AF and infrequent falls. Stroke risk is higher than intra- cerebral bleeding. Treatment Specific interventions for community-dwelling older adults: o Prescribe exercise programs that emphasize balance, gait, and strength training (physical therapy or tai chi). o Assess and modiSr the home environment. . Reduce polypharmacy (particularly psychoactive medications). r Treat orthostasis and visual impairments. DOil'T BE TRICKED . The USPSTF recommends against vitamin D supplementation to prevent falls in community-dwelling adults >65 years who are not known to have osteoporosis or vitamin D deficiency. . Hip protectors in older people who fall are ineffective in preventing hip fractures. 140

General lnternal Medicrne TESTYOURSELF An 80 year-old woman presents after a mechanical fall at home. Her medications are clonazepam, amlodipine, levothyroxine, and pantoprazole. ANSWER: For management, choose to discontinue clonazepam, check orthostatic BP, and provide risk factor modification. Urinary lncontinence STUDY TABLE: Diagnosis and Treatment of Urinary lncontinence and Related Conditions lf you see this... Diagnose this... Choose this... Sudden urge to void preceding or accompanied by Urge incontinence First-line therapy is bladder training; second-line leakage of urine therapy is anticholinergic drugs (e.9., oxybutynin, tolterodine) or a B-adrenergic (mirabegron) lnvoluntary release of urine with increased Stress incontinence First-line therapy is pelvic floor muscle training for abdominal pressure (sneezing, coughing, physical women ( Kegel exercises) exertion) Urgency and stress incontinence Mixed incontinence Bladder training and pelvic floor muscle training Unable to get to bathroom on time because of Functional inconti nence Portable commode, regular prompted urination mental or physical limitations with physical assistance to commode, treatment of underlying disorders Nearly constant dribbling of urine, incomplete Overflow incontinence Double voiding, triggered (timed) urination, emptying of bladder, high postvoiding residual urine intermittent bladder catheterization Women with obesity and either urge or stress incontinence will benefit from weight loss and exercise. Topical vaginal estrogen may benefit women with stress incontinence and genitourinary symptoms of menopause. DOil'T BE TRICKED . Do not prescribe systemic estrogen-progestin therapy because it may worsen stress and urge incontinence. o Do not order urodynamic testing because outcomes are no better than those associated with management based on clinical evaluation alone.

Women with obesity and either urge or stress incontinence will benefit from weight loss and exercise. Topical vaginal estrogen may benefit women with stress incontinence and genitourinary symptoms of menopause. DOil'T BE TRICKED . Do not prescribe systemic estrogen-progestin therapy because it may worsen stress and urge incontinence. o Do not order urodynamic testing because outcomes are no better than those associated with management based on clinical evaluation alone. TEST YOURSETF A 78 year-old woman has urinary urgency, nocturia, and urine loss with coughing and sneezing. Her medical history includes HF and glaucoma. ANSWER: For diagnosis, select mixed incontinence. For management, choose initiation of pelvic muscle exercises and bladder training techniques. Pressure lnjury Prevention Systematic identification of persons at risk, pressure redistribution, and use of advanced static mattresses or overlays can pre vent pressure injury. An advanced static mattress is made of specialized sheepskin, foam. or gel and is immobile when a patient lies on it, whereas an advanced static overlay is a pad composed of foam or gel that is secured to the top of a regular mattress. Diagnosis Pressure injuries are ischemic soft tissue injuries resulting from pressure, usually over bony prominences. The external appear- ance may underestimate the extent of the injury. 141

General lnternal Medicine STUDY TABLE: Pneumococcal lmmunization Risk Group PCVI 3 PPSV23 Recommended Recommended Revaccination With PPSV23 at 5 Yearc After First Dose lmmunocompetent adults age >65 y Based on shared Yes, 1 year after Only if originally decision-making PCV13, if given immunized before age 65 y lmmunocompetent persons with chronic heart, lung, or liver disease; No Yes Only if originally diabetes mellitus; alcoholism; cigarette smoking immunized before age 65 y Persons with functional (sickle cell disease, hemoglobinopathies) or Yes Yes Yes anatomic asplenia lmmunocompromised persons: congenital or acquired Yes Yes Yes immunodeficiencies and phagocytic disorders; HIV; CKD; nephrotic syndrome; leukemia; lymphoma; Hodgkin lymphoma; generalized malignancy; diseases requiring treatment with immunosuppressive drugs, including long-term systemic alucocorticoids and radiation therapy; solid-organ transplant recipients; multiple myeloma CSF leaks or cochlear implants Yes Yes No

STUDY TABLE: Pneumococcal lmmunization Risk Group PCVI 3 PPSV23 Recommended Recommended Revaccination With PPSV23 at 5 Yearc After First Dose lmmunocompetent adults age >65 y Based on shared Yes, 1 year after Only if originally decision-making PCV13, if given immunized before age 65 y lmmunocompetent persons with chronic heart, lung, or liver disease; No Yes Only if originally diabetes mellitus; alcoholism; cigarette smoking immunized before age 65 y Persons with functional (sickle cell disease, hemoglobinopathies) or Yes Yes Yes anatomic asplenia lmmunocompromised persons: congenital or acquired Yes Yes Yes immunodeficiencies and phagocytic disorders; HIV; CKD; nephrotic syndrome; leukemia; lymphoma; Hodgkin lymphoma; generalized malignancy; diseases requiring treatment with immunosuppressive drugs, including long-term systemic alucocorticoids and radiation therapy; solid-organ transplant recipients; multiple myeloma CSF leaks or cochlear implants Yes Yes No STUDY TABLE: Meningococcal Vaccines for Persons at lncreased Risk of Meningococcal Disease Population MenACVl/Y MenB Persistent complement component Primary vaccination followed by booster Primary vaccination followed by booster deficiencies (C5-C9, faaor H, faaor D, every 5 years 1 year later and every 2-3 years thereafter properdin, or patients taking eculizumab) Functional or anatomic asplenia (including Primary vaccination followed by booster Primary vaccination followed by booster sickle cell disease) every 5 years 1 year later and every 2-3 years thereafter

STUDY TABLE: Meningococcal Vaccines for Persons at lncreased Risk of Meningococcal Disease Population MenACVl/Y MenB Persistent complement component Primary vaccination followed by booster Primary vaccination followed by booster deficiencies (C5-C9, faaor H, faaor D, every 5 years 1 year later and every 2-3 years thereafter properdin, or patients taking eculizumab) Functional or anatomic asplenia (including Primary vaccination followed by booster Primary vaccination followed by booster sickle cell disease) every 5 years 1 year later and every 2-3 years thereafter HIV infection Primary vaccination followed by booster Same as general population every 5 years M icrobiologists routinely exposed to Primary vaccination followed by booster Primary vaccination followed by booster Neisseria me ni ngitidis every 5 years 1 year later and every 2-3 years thereafter Exposure to vaccine-preventable Single dose if >5 years since vaccination Primary vaccination; booster if >1 year serogroup meningococcal disease since primary series outbreak Travel or residence in country with Primary vaccination followed by booster Same as general population hyperendemic or epidemic every 5 years meningococcal disease College freshmen living in residency halls Primary vaccination Same as general population Military recruits Primary vaccination followed by booster Same as general population every 5 years (depending on military assignment) Aspirin and Prevention Aspirin is recommended by the USPSTF for primary prevention of ASCVD and colon cancer if all the following apply: . adult aged 50-59 years . 10 year CVD risk >10'/, o life expectancy >10 years . no increased bleeding risk o willing to take low dose aspirin daily for >10 years

Exposure to vaccine-preventable Single dose if >5 years since vaccination Primary vaccination; booster if >1 year serogroup meningococcal disease since primary series outbreak Travel or residence in country with Primary vaccination followed by booster Same as general population hyperendemic or epidemic every 5 years meningococcal disease College freshmen living in residency halls Primary vaccination Same as general population Military recruits Primary vaccination followed by booster Same as general population every 5 years (depending on military assignment) Aspirin and Prevention Aspirin is recommended by the USPSTF for primary prevention of ASCVD and colon cancer if all the following apply: . adult aged 50-59 years . 10 year CVD risk >10'/, o life expectancy >10 years . no increased bleeding risk o willing to take low dose aspirin daily for >10 years The ACC/AHA and the ADA recommend that aspirin may be considered for primary prevention of ASCVD in adults aged 40 to 70 years who are at higher ASCVD risk but not at increased bleeding risk. 144

General lnternal Medicine STUDY TABLS: U5PSTF-Recommended Screening Condition Screening Recommendation Chronic Diseases Abdominal aortic aneurysm One-time abdominal ultrasonography in all men aged 65-75 y who have ever smoked; selectively screen men aged 65-75 y who have never smoked Depression All adults, when staff-assisted depression care support is available Diabetes mellitus Ages 35-70 years with overweight or obesity as part of risk assessment for CVD Hypertension Annual screening for adults aged >40 y and for those at increased risk, including those with BP 130-139/85-89 mm Hg, with overweight or obesity, and Black persons. Adults aged 1B-39 y with BP <1 30/85 mm Hg who do not have other risk factors should be rescreened every 3-5 years. Lipid disorders Universal lipid screening in adults aged 40-75 y as part of risk assessment for CVD Osteoporosis Women aged >65 y; postmenopausal women aged <65 y when 1 0-year fracture risk is increased as determined by a formal clinical risk assessment tool (e.9., >8.4%) lnfectious Diseases Chlamydia and gonorrhea All sexuallyactivewomen aged<24y; all sexuallyactiveolderwomenatincreasedriskof infection HCV One-time screening for adults aged 18-79 y; periodically in all adults at high risk HIV infection One-time screening for all adults aged 1 5-65 y; at least annually for adults at high risk HBV infection, syphilis, latent TB All adults at high risk Substance Abuse i Alcohol misuse All adults

Lipid disorders Universal lipid screening in adults aged 40-75 y as part of risk assessment for CVD Osteoporosis Women aged >65 y; postmenopausal women aged <65 y when 1 0-year fracture risk is increased as determined by a formal clinical risk assessment tool (e.9., >8.4%) lnfectious Diseases Chlamydia and gonorrhea All sexuallyactivewomen aged<24y; all sexuallyactiveolderwomenatincreasedriskof infection HCV One-time screening for adults aged 18-79 y; periodically in all adults at high risk HIV infection One-time screening for all adults aged 1 5-65 y; at least annually for adults at high risk HBV infection, syphilis, latent TB All adults at high risk Substance Abuse i Alcohol misuse All adults L Tobacco use All adults t Cancer i I Breast cancer Biennial screening mammography for women aged 50-74 y; initiation of screening before age 50 y t should be individualized L Cervical cancer Women aged 21-65 y with cytology (Pap smear) every 3 y; in women aged 30-65 y who want to lengthen screening, screen with cytology and HPVtesting every 5 y or high-risk HPVtesting alone every 5 y Do not screen women following hysterectomy and cervix removalfor benign disease I

L Tobacco use All adults t Cancer i I Breast cancer Biennial screening mammography for women aged 50-74 y; initiation of screening before age 50 y t should be individualized L Cervical cancer Women aged 21-65 y with cytology (Pap smear) every 3 y; in women aged 30-65 y who want to lengthen screening, screen with cytology and HPVtesting every 5 y or high-risk HPVtesting alone every 5 y Do not screen women following hysterectomy and cervix removalfor benign disease I I Colon cancer All adults aged 45-75 y. USPSTF recommendations do not support one form of screening test over another for detecting early stage CRC in average-risk patients. Available tests include stool-based, direct visuallzation, and serology tests (see Study Table: USPSTF Colon Cancer Screening lntervals for Average-Risk Patients). Annual low-dose CT scan in high-risk patients (adults aged 50-80 y with a 20-pack-year smoking t Lung cancer history, including former smokers who have quit in the last 15 years) I Prostate cancer Men aged 55-69 years should make an informed decision about prostate cancer screening with their i physician. Physicians should not screen men unless they express a preference for screening, and routine screening for men >70 years is recommended against.

Prostate cancer Men aged 55-69 years should make an informed decision about prostate cancer screening with their i physician. Physicians should not screen men unless they express a preference for screening, and routine screening for men >70 years is recommended against. L STUDY TABLS: USPSTF Colon Cancer Screening lntervals forAverage-Risk Patients ; Method lnterval Guaiac fecal occult blood test (FOBT) Annually Fecal immunochemical test (FlT) Annually FIT-DNA Every1 or3years Flexible sigmoidoscopy Every 5 years Flexible sigmoidoscopy plus annual FIT Every 1 0 years Colonoscopy Every 1 0 years CT colonography Every 5 years 145

General lnternal Medicine STUDY TABLI: Select lndications for Preoperative LaboratoryTesting Laboratory Tesli Preoperative lndications Hemoglobin History of anemia Signs/symptoms or examination findings suggesting anemia Underlying disease that predisposes to anemia (e.9., kidney disease, myelodysplasia) Expected substantial operative blood loss Platelet count History of thrombocytopenia or cirrhosis; signs or symptoms of bleeding or liver disease Coagulation studies Warfarin or heparin use History of abnormal bleeding Medical conditions that predispose to coagulopathy (e.g., liver disease, nutritional disorders, hemophilia) Elearolytes Diseases that predispose to electrolyte derangements (e.g., kidney disease) Use of medications that can cause electrolyte abnormalities (e.g., diuretics, ACE inhibitors, ARBs)

STUDY TABLI: Select lndications for Preoperative LaboratoryTesting Laboratory Tesli Preoperative lndications Hemoglobin History of anemia Signs/symptoms or examination findings suggesting anemia Underlying disease that predisposes to anemia (e.9., kidney disease, myelodysplasia) Expected substantial operative blood loss Platelet count History of thrombocytopenia or cirrhosis; signs or symptoms of bleeding or liver disease Coagulation studies Warfarin or heparin use History of abnormal bleeding Medical conditions that predispose to coagulopathy (e.g., liver disease, nutritional disorders, hemophilia) Elearolytes Diseases that predispose to electrolyte derangements (e.g., kidney disease) Use of medications that can cause electrolyte abnormalities (e.g., diuretics, ACE inhibitors, ARBs) Creatinine Kidney disease Expected large intraoperative fluid and BP shifts Used in preoperative cardiovascular risk calculators and for calculation of the MELD score Liver chemistry tests (including bilirubin) Cirrhosis, history of abnormal liver chemistry tests, or signs or symptoms of liver disease Fasting glucose and hemoglobin ,A1. Known or suspected diabetes mellitus Urinalysis Suspected UTI Planned urologic procedures Pregnancy test Women of childbearing age "lf patient is clinically stable and has no medication changes, tests other than pregnancy test need not be repeated if performed within 4 months of procedure.

Creatinine Kidney disease Expected large intraoperative fluid and BP shifts Used in preoperative cardiovascular risk calculators and for calculation of the MELD score Liver chemistry tests (including bilirubin) Cirrhosis, history of abnormal liver chemistry tests, or signs or symptoms of liver disease Fasting glucose and hemoglobin ,A1. Known or suspected diabetes mellitus Urinalysis Suspected UTI Planned urologic procedures Pregnancy test Women of childbearing age "lf patient is clinically stable and has no medication changes, tests other than pregnancy test need not be repeated if performed within 4 months of procedure. C,a rdiovascu la r Risk Assessment Risk factors for a major adverse cardiac event (MACE) include: . known CAD, cerebrovascular disease (CVA, TIA) . CKD o diabetes mellitus .HF Patients with risk factors should undergo estimation of MACE risk using a validated risk calculator such as the Revised Cardiac Risk Index. Patients with an elevated risk of MACE >l% should have their functional capaclty assessed with a standardized tool such as the Duke Activity Status Index. Patients with functional capacity >5 METs are low risk and can proceed to surgery. Otherwise, preoperative cardiac stress testing should be considered but only if the results will change perioperative management. Obtain an ECG within 1 to 3 months of surgery (except low-risk surgery) in any patient with: . CAD o significant arrhl4hmias o cerebrovascular disease (stroke or TIA) O PAD DOil'T BETRICKED . If a patient has no history, symptoms, or risk factors for CAD, no preoperative coronary evaluation is necessary. . Low-risk surgeries (cataract extraction, carpal tunnel release, breast biopsy, inguinal hernia repair) do not require cardiac testing even ifa calculated risk score is elevated. 148

General lnternal Medicine o AF with moderate to severe mitral stenosis . older generation mechanical valves (ball-cage or tilting disc) o recent thromboembolic event (e.9., CVA, TIA, VTE within previous 3 mo) e aortic mechanical valve plus additional risk factor for thrombosis o moderate to severe mitral stenosis Stopping and restarting perioperative anticoagulation: o Stop UFH 4 to 6 hours before surgery. o Stop LMWH 12 hours before surgery. . Restart heparin 24 hours after surgery. . Restart warfarin 12 to 24 hours after surgery. . Restart dabigatran, rivaroxaban, and apixaban 24 hours after surgery. Perioperative Management of Anti platelet Thera py Dual antiplatelet therapy should be continued: . 14 to 30 days after bare-metal stent placement for stable CAD o 3 to 6 months after drug eluting stent placement for stable CAD . 21 year in patients following ACS Dual antiplatelet therapy should be restarted as soon as possible postoperatively. Obesity Diagnosis STUOY ?*BLE: Obesity Definitions Diagnosis BMI Overweight 2s-29.9 Obese Class I 30-34.9 Class ll 35-39.9 Class lll >40 Waist circumference >102 cm (40 in) in men and >88 cm (sS in) in women correlates with visceral adiposity and increased risk for diabetes, CVD, and all cause mortality. Laboratory evaluation should include: r thyroid and liver function . Iipid levels o screening for diabetes Cancer screening recommendations are the same as for patients without obesity. Screening for CVD is reserved for symptomatic patients. 150

General lnternal Medicine Erectile Dysfunction Diagnosis The most common causes include vascular disease, neurologic disease, medications, androgen deficiency, and psychologic issues. Along with medications (e.9., antidepressants, p blockers) . look for alcohol, tobacco, cocaine, opioid. or marijuana use. Psychogenic dysfunction is common and may coexist with other causes. Erectile dysfunction occurring with preserved ability to achieve nocturnal and early morning erections should raise suspicion for psychogenic cause. Testing Obtain a morning total testosterone level for all patients. Suspect androgen steroid abuse in patients with infertility, muscular hypertrophy, testicular atrophy, and acne; laboratory data show elevated hemoglobin and suppressed LH and FSH levels. Treatment Nonpharmacologic treatment options include lifestyle modifications, such as smoking cessation, exercise, and weight optimiza tion. First line pharmacotherapy for erectile dysfunction is oral PDE-5 inhibitors (sildenafil, vardenafil [on demand], or tadalafil [daily]). These drugs are contraindicated in men who receive nitrate therapy in any form and in men with a history of nonarte ritic anterior ischemic optic neuropathy. They should be used with caution in men taking cr blockers because of the risk of hypotension. Intraurethral or intracavernous alprostadil is a second-line therapy for men who cannot take PDE-5 inhibitors. Testosterone therapy is reserved for patients with confirmed hypogonadism. TESTYOURSETF A 72-year-old man cannot maintain an erection. He has diabetes mellitus, peripheral vascular disease, and CAD with stable angina, for which he takes aspirin, atenolol, isosorbide dinitrate, and glipizide. ANSWER: For management. choose intraurethral or intracavernous alprostadil initiation. Benign Prostatic Hyperplasia Diagnosis BPH leads to irritative symptoms (urinary urgency, flrequency, and nocfuria) and obstructive symptoms (decreased urinary stream, intermittency, incomplete emptying, and straining). BPH is diagnosed primarily by medical history and is supported by digital rectal examination. When a diagnosis of BPH has been established, the American Urological Association Symptom Index quantifies symptom severity and guides treatment decisions.

Benign Prostatic Hyperplasia Diagnosis BPH leads to irritative symptoms (urinary urgency, flrequency, and nocfuria) and obstructive symptoms (decreased urinary stream, intermittency, incomplete emptying, and straining). BPH is diagnosed primarily by medical history and is supported by digital rectal examination. When a diagnosis of BPH has been established, the American Urological Association Symptom Index quantifies symptom severity and guides treatment decisions. Treatment For most patients, conservative treatment is sufficient (reduce fluid intake, stop contributing medications [diuretics, anticho linergicsl). The two major BPH drug classes include: . cr adrenergic blockers (terazosin, tamsulosin, doxazosin, alfuzosin, and prazosin) . 5 o reductase inhibitors (finasteride, dutasteride) o Adrenergic blockers are superior to 5-o. reductase inhibitors. cx-Adrenergic blockers plus finasteride are more effective than either drug alone but are associated with increased adverse effects. 152

General lnternal Medicine Tadalafil, a PDE 5 inhibitor, improves lower urinary tract symptoms and may be used in patients with concomitant BPH and erectile dysfunction. Surgical treatment is indicated in patients with severe urinary symptoms, urinary retention, persistent hematuria, recurrent UTIs, or kidney disease clearly attributable to BPH. DON'T BE TRICKED . Do not choose saw palmetto to treat lower urinary tract symptoms because of a lack of data supporting efficacy t Acute Scrotal Pain Diagnosis I Patients with testicular torsion have severe acute pain. Absence ofthe cremasteric reflex on the aflected side is nearly 99oL sensitive for torsion. The testis is usually high within the scrotum and may lie transversely. Doppler flow ultrasonography I I demonstrates diminished blood flow to the affected testicle. Testicular elevation will not relieve pain. Epididymitis causes pain localizing to the posterior and superior aspects of the testicle. Pain onset is subacute and may be i accompanied by dysuria, pyuria, and fever. The scrotum may be edematous and erythematous. Pain may decrease with testicu lar elevation. Orchitis is usually caused by viral infection (mumps) or extension of a bacterial infection from epididymitis or UTI. The testicle I is diffusely tender. In epididymitis and orchitis, ultrasonography demonstrates normal or increased blood flow to the testicle and epididymis. Treatment Treatment of testicular torsion is immediate surgical exploration and reduction. ln men younger than 35 years with epididymitis, treat for gonorrhea and chlamydial infection (ceftriaxone and doxycycline). In men older than 35 years at low risk for STIs, treat with levofloxacin; for all men engaging in anal intercourse, treat with ceftriaxone and oral levofloxacin. Acute Prostatitis Diagnosis Symptoms of acute prostatitis include fever, chills, dysuria, pelvic pain, cloudy urine, obstructive symptoms, and blood in the semen. Septic shock may be a presenting feature in some men. The diagnosis is established by finding a tender prostate on physical examination and a positive urine culture.

Acute Prostatitis Diagnosis Symptoms of acute prostatitis include fever, chills, dysuria, pelvic pain, cloudy urine, obstructive symptoms, and blood in the semen. Septic shock may be a presenting feature in some men. The diagnosis is established by finding a tender prostate on physical examination and a positive urine culture. Treatment Begin empiric antibiotics that cover gram negative organisms (trimethoprim sulfamethoxazole, fluoroquinolone) for 2 to 6 weeks. For patients who appear toxic, hospitalize and add gentamicin to a fluoroquinolone, cefotaxime, ceftazidime, or piperacillin /tazobactam. 153

General lnternal Medicine Abnormal Uterine Bleeding Diagnosis First, exclude pregnancy; then, classi$r bleeding as either ovulatory or anolrrlatory. Ovulatory bleeding occurs at regular intervals, but the menstrual flow is excessive. Common causes: . thyroid disease o bleeding disorder . structural abnormalities (uterine fibroids or polyps) Anovulatory cycles are characteristically irregrrlar in terms offlow and cycle duration because lack ofovulation and the result- ant lack of cyclic progesterone cause endometrial hyperplasia and irregular bleeding. Common causes: . PCOS . hypothyroidism or hyperthyroidism . hyperprolactinemia Initial laboratory testing includes pregnancy test and CBC. Additional testing is directed by clinical indications and may include coagulation tests and TSH, iron, and hormone levels. Endometrial biopsy is indicated in postmenopausal women. Pelvic ultrasonography is an option to assess for structural abnor- malities in the uterus and to determine endometrial thickness. In postmenopausal women, endometrial biopsy is indicated if the endometrial thickness is >4 mm on ultrasound. Treatment Management of abnormal uterine bleeding is aimed at the underlying cause. o Structural abnormalities may be surgically resected. o Treat endocrine disorders (thyroid disease, PCOS). For women with ano'".trlatory cycles who wish to preserve fertility: . medroxyprogesterone acetate used for the second half of the menstrual cycle will restore cyclic withdrawal bleeding. For women interested in contraception: o combined oral contraceptive pills or o levonorgestrel intrauterine device may be used DO]I'T BETRICKED . Pregnancy, including ectopic pregnancy, should always be considered in the differential diagnosis of abnormal uterine bleeding. . Postmenopausal bleeding is always abnormal and requires evaluation. 156

I I General lnternal Medicine L I t i Dysmenorrhea Diagnosis Symptoms of dysmenorrhea include abdominal cramps, backache, headache, nausea, vomiting, and diarrhea. Symptoms coin- cide with the onset of menses and last 2 to 3 days. Dysmenorrhea is classified as primary or secondary. Primary dysmenorrhea, which occurs in 90'1, of patients, is associated with normal ovulatory cycles and no pelvic pathologz. A secondary cause, such as endometriosis, fibroids, or uterine pathologz, is found in 10'7, of patients. Dysmenorrhea is sometimes associated with other cyclic symptom complexes such as PMS and PMDD. These disorders include physical and psychological symptoms that begin approximately 1 week before menses and cease with menstruation. PMDD is characterized by significant depressive symptoms that interfere with daily activities. Initial evaluation includes a thorough history with attention to risks for STI and possible physical, sexual, or emotional abuse. Treatment Primary dysmenorrhea is treated symptomatically without further testing with NSAIDs and COX-2 inhibitors. Second-line therapy includes combined hormonal contraceptive therapy. Fluoxetine, sertraline, and paroxetine are effective first line treatments for PMS and PMDD. Menopause Diagnosis Menopause describes the cessation of menses and fertility and is definitive when a woman has experienced amenorrhea for 12 months. Major symptoms of menopause include vasomotor symptoms (hot flushes, night sweats) and genitourinary symp- toms (vaginal dryness, dyspareunia). DON'T BE TRICKED . Do not order hormone levels to diagnose menopause. Treatment Vasomotor symptoms generally resolve spontaneously within a few years, and treatment should be based on symptom severity. In patients with severe symptoms, the most effective treatment is systemic hormone therapy, which can be used in healthy women aged <60 years and within 10 years of menopause. Keep these treatment points in mind when using estrogen:

Treatment Vasomotor symptoms generally resolve spontaneously within a few years, and treatment should be based on symptom severity. In patients with severe symptoms, the most effective treatment is systemic hormone therapy, which can be used in healthy women aged <60 years and within 10 years of menopause. Keep these treatment points in mind when using estrogen: r Contraceptive needs must be addressed during perimenopause. . Transdermal estrogen may be associated with less VTE risk than oral estrogen. o All women with an intact uterus must receive progestin. o Duration of treatment >5 years is associated with increased risk of breast cancer. o The need fbr continued treatment should be reevaluated annually. Common contraindications to hormone therapy include pregnancy, unexplained vaginal bleeding, liver disease, CAD, stroke, VTE, breast cancer, and endometrial cancer. 157

General lnternal Medicine Nonhormonal options for women with vasomotor symptoms and contraindications to hormone therapy include low dose antidepressant agents (venlafaxine, desvenlafaxine, paroxetine, citalopram, and escitalopram) and gabapentin. In the absence of systemic estrogen therapy, genital symptoms can be treated with vaginal lubricants (first line) or topical estro- gen (vaginal atrophy). DOI{'T BE TRICKED . Data regarding black cohosh are inconclusive, as are studies ofother herbs, soy, and other phytoestrogens. . The USPSTF and other guidelines recommend against using hormonal therapy for the primary prevention of chronic conditions (such as osteoporosis) in postmenopausal women. Chronic Pelvic Pain Chronic pelvic pain is ongoing pelvic pain that has been present for 3 to 6 months in the absence of pregnancy. STUDY fABLE: Differential Diagnosis of Chronic Pelvic Pain If you see this... Diagnose this... Pelvic heaviness, abnormal uterine bleeding, infertiliry and enlarged uterus on bimanual Uterine fibroids examination or ultrasonography Chronic pelvic pain worse before and during menses, associated with dysmenorrhea Endometriosis History of sexual abuse and normal physical examination and ultrasonography Chronic pelvic pain syndrome relieved with lnterstitial cystitis Testing A urine pregnancy test and pelvic/transvaginal ultrasonography are used to evaluate women with chronic pelvic pain DOil'T BE TRICKED . Additional evaluation is warranted in a patient with chronic pelvic pain who has a sudden increase in pain intensity, which may indicate a superimposed acute process such as appendicitis. Endometriosis Endometriosis is characterized by ectopic endometrial implants, usually in the pelvis, but they can be found anlwhere and cause cyclic bleeding, such as in the lungs (hemoptysis), CNS (catamenial headache), and rectum (rectal bleeding during menses). Physical examination findings may be normal or may include abdominal masses and tenderness and abnormalities of the cervix. uterus, and adnexa. Also look for abnormalities of uterosacral ligaments on bimanual examination.

Endometriosis Endometriosis is characterized by ectopic endometrial implants, usually in the pelvis, but they can be found anlwhere and cause cyclic bleeding, such as in the lungs (hemoptysis), CNS (catamenial headache), and rectum (rectal bleeding during menses). Physical examination findings may be normal or may include abdominal masses and tenderness and abnormalities of the cervix. uterus, and adnexa. Also look for abnormalities of uterosacral ligaments on bimanual examination. The lesions can be visualized by laparoscopy, the gold standard for diagnosis, but it is not required for medical treatment when other causes of pelvic pain have been ruled out. DOil'T BE TRICKED . Endometriosis does not cause fever or vaginal discharge. Treatment NSAIDs are first-line therapy for endometriosis, followed by oral contraceptives if pregnancy is not desired. 158

General lnternal Medicine Candlda alblaas: This wet mount specimen exhibits the typical filaments and Cluc Ccll: Ihis image shows clue cells (epithelial cells with borders obscured by spores associated with candidal vaginitis. small bacteria) on saline microscopy that are consistent with bacterial vaginosis. DOTT II TRICKID o Do not order vaginal cultures to diagnose the cause ofvaginitis. . Treatment of vulvovaginal candidiasis can be initiated empiricdly if symptoms are accompanied by characteristic findings. Trcatment Treating V.:grnitrs lf tte diagnosis is... Treatwith.. of Complicated vagina I candidiasis (severe non-albicans Candida species, >4 episodes/y, u diabetes mellitus, immunosuppression Ba@ialvagii,$ai3 '. '. ,: Oral or topical metronidazole or topical clindarvryc&r (s# during , , prcg.lafiy) .,1 Trichomoniasis Oral metronidazole and also for male partner (safe during pregnancy). Test for other STls. Retest within 3 months of treatment. DOX'T 3t TNrcKED r Because vagtnal yeast is found in 10"/" to 2ool" of healthy women, the identification of Condido species in patients without symptoms does not require treatment. Tr3r vounsttF A 2l.-year-old woman has a vaginal discharge and odor. Pelvic examination shows a thin, white homogeneous vaginal discharge with a normal cervix and normalvaginal mucos€l. Wet mount is negative for TrichomonasandC,andida. Vaginal pH is 6.0. AllS\ilER: For diagnosis, choose bacterial vaginosis. 160

General lnternal Medicine SIUDY ?ABIE: Causes andTreatment of Red Eye (Continued) lf you see this... Diagnose this.. Do this... Conjunctivitis associated with herpes Herpes zoster conjunctivitis Eme rge ncy ophtha I mo o gy referra I I zoster rash involving ophthalmic division of {ifth cranial nerve Acute hyperpurulent discharge in a Neisseria gono rrh oe a e conj u nctivitis Topical and systemic antibiotics and sexually active adult emergency ophtha mology referra I I Unilateral then bilateral conjunctivitis with Viral conjunctivitis Supportive care daytime watery or mucoid discharge Itching and tearing ofthe eyes, nasal Allergic conjunctivitis Topical vasoconstrictors, antihista mi nes, congestion mast cell stabilizers (e.g., cromolyn)

Unilateral then bilateral conjunctivitis with Viral conjunctivitis Supportive care daytime watery or mucoid discharge Itching and tearing ofthe eyes, nasal Allergic conjunctivitis Topical vasoconstrictors, antihista mi nes, congestion mast cell stabilizers (e.g., cromolyn) Severe eye discomfort with difficulty Keratitis Emergency ophthal mology referral keeping the affected eye open, blurred or diminished vision, photophobia, circumferential redness (ciliary flush) at the corneal limbus (junction of the cornea and sclera) Unilateral deep ocular pain, nausea, Acute angle-closure glaucoma Emergency ophthalmology referral for vomiting, fixed nonreactive pupil, shallow iridotomy; topical agents to lower anterior chamber intraocular pressure Severe ocular pain that worsens with eye Scleritis Emergency ophtha lmology referra l; movement and light exposure; a raised consider RA and vasculitis hyperemic lesion that may be localized or diffuse and obscures the underlying vasculature Localized nonpainful red, flat, superficial Episcleritis Self-limited; no treatment required lesion that allows visualization of the underlying vasculature Circumferential redness (ciliary flush) at the lritis (anterior uveitis) Emergency ophtha lmology referral; corneal limbus (junction o{the cornea and consider ankylosing spondylitis and sclera), hypopyon may be visible, pupil reactive arthritis may be irregular DON'T BETRICKED . Do not treat a red eye with topical glucocorticoids.

Severe eye discomfort with difficulty Keratitis Emergency ophthal mology referral keeping the affected eye open, blurred or diminished vision, photophobia, circumferential redness (ciliary flush) at the corneal limbus (junction of the cornea and sclera) Unilateral deep ocular pain, nausea, Acute angle-closure glaucoma Emergency ophthalmology referral for vomiting, fixed nonreactive pupil, shallow iridotomy; topical agents to lower anterior chamber intraocular pressure Severe ocular pain that worsens with eye Scleritis Emergency ophtha lmology referra l; movement and light exposure; a raised consider RA and vasculitis hyperemic lesion that may be localized or diffuse and obscures the underlying vasculature Localized nonpainful red, flat, superficial Episcleritis Self-limited; no treatment required lesion that allows visualization of the underlying vasculature Circumferential redness (ciliary flush) at the lritis (anterior uveitis) Emergency ophtha lmology referral; corneal limbus (junction o{the cornea and consider ankylosing spondylitis and sclera), hypopyon may be visible, pupil reactive arthritis may be irregular DON'T BETRICKED . Do not treat a red eye with topical glucocorticoids. TESTYOURSETF A 39-year-old man has bilateral red eyes and pain for 2 days. He has arthritis and chronic low back pain. Visual acuity is 20140 bilaterally. Eyes are intensely injected, with prominent circum- corneal erlthema. ANSWER: For diagnosis, choose acute iritis associated with anky losing spondylitis. For management, select emergent referral to an ophthalmologist.

TESTYOURSETF A 39-year-old man has bilateral red eyes and pain for 2 days. He has arthritis and chronic low back pain. Visual acuity is 20140 bilaterally. Eyes are intensely injected, with prominent circum- corneal erlthema. ANSWER: For diagnosis, choose acute iritis associated with anky losing spondylitis. For management, select emergent referral to an ophthalmologist. Bacterial Conjunctivitis:The conjunctiva is diffusely erythemat0us with mucopu- rulent discharge consistent with bacterial conjunctivitis. Consider gonorrhea in sexually active adult. 162

I General lnternal Medicine Herpes Zoster: Herpes zoster infection Viral Conjunctivitis: Acute adenovi rus conjunctivitis Allergic Conjunctivitis: Allergic conjunctivitis with prominent involving the forehead, top of the head, and is characterized by diffuse injection of the palpebral cobblestoning of the palpebral conjunctiva is shown. eye, with evident hyperemic conjunctivitis. and bulbar conjunctivae and pseudomembrane forma' Corneal ulceration, episcleritis, and lid tion involving the palpebral conjunctiva. droop can occur. Episcletitis: Ihe nontender, prominent, superficial dilated blood vessels lritis: lntense ciliary flush around the corneal-scleral junction and an irregularly shaped of episcleritis are shown. pupil are characteristic of iritis. Age-Related Macular Degeneration Dry AMD involves the deposition of extracellular material (drusen) in the macular region olone or both eyes and may cause diminished visual acuity. Smoking cessation is imperative. Progression of advanced dry AMD may be slowed with the use of zinc or antioxidant supplements. A small percentage of patier.rts with dry AM I) will progress to develop new vessel growth uncier the retina (wet AM D). Bleeding and exudation results in sudden (or rapid onset over weeks), painless blurring or warping of central vision. l-aser pl.rotocoagula tion and intraocular injection of VEGF inhibitors are recommended fbr wet AMD. Retinal Detachment Retinal cletachnrent occurs mainly in myopic patients. Sympton.rs are floaters. flashes of light (photopsias), and squiglly lines, followed by a sudden, peripheral visual field defect that resembles a black curtain and progresses across the entire visual fleld. Emergent ophthalmologr referral is crucial. as prognosis depends on the time to surgical treatment. 163

General lnternal Medicine Treatment Topical treatments, including antibiotics, glucocorticoids, antiseptics (acetic acid), and combination therapies, are first-line management for uncomplicated acute external otitis. Select systemic antipseudomonal antibiotics and hospitalization for malig nant external otitis, and antiviral agents for Ramsay Hunt syndrome. TESTYOURSELF A 70 year-old man with type 2 diabetes mellitus has had a severe left earache since yesterday. He has a fever and tachycardia, and his left external ear canal is swollen. Moist, white debris and granulation tissue are visible. ANSWER: For diagnosis, choose malignant external otitis. For management, select hospitalization and IV ciprofloxacin. Sinusitis Diagnosis Viral infection causes most cases of sinusitis. Bacterial sinusitis is more likely if the following are present: o persistent symptoms (lasting >10 days) . severe symptoms or high fever (lasting 3-4 days) . "double sickness," characterized by worsening symptoms following a period of improvement over 3 to 4 days Complications of acute sinusitis are unusual but deadly. Patients with cavernous sinus thrombosis have fever, nausea, vomiting, headache, orbital edema, or cranial nerve involvement. Other complications include brain abscess, bacterial meningitis, and osteomyelitis. Testing Imaging, including CT, should be considered in patients with AIDS or in other immunocompromised patients to evaluate for fungal infection or other atypical infections but is not otherwise indicated. Treatment Symptomatic therapies include topical decongestants, saline nasal irrigation, mucolltics, intranasal glucocorticoids, and anti- histamines. The first-line choice for suspected bacterial sinusitis is amoxicillin-clavulanate or amoxicillin. Allergic Rhinitis Diagnosis Rhinitis is an inflammation of the nasal mucosal membranes that causes rhinorrhea, nasal itching, sneezing, nasal congestion, and postnasal drainage. Allergic rhinitis can be seasonal or perennial. Diagnosis of allergic rhinitis is usually made by history and confirmed with empiric treatment. If empiric treatment fails, diagnostic allergz testing may be appropriate to guide allergen avoidance or immu- notherapy. Allergy skin testing is preferred to in vitro specific IgE antibody assay (or RAST). 166

General lnternal Medicine STUDY TABLE: Mimics of Allergic Rhinitis Look for... Diagnose... Young person, nasal polyposis, chronic sinusitis, malnourishment, Cystic fibrosis infertility, and chronic or recurrent bronchitis Nonseasonal rhinitis with negative skin tests Chronic nonallergic rhinitis (vasomotor rhinitis) Refractory congestion after chronic use of topical nasal Rhinitis medicamentosa decongestants Rhinitis, nasal polyps, asthma, and aspirin intolerance (respiratory Aspirin-exacerbated respiratory disease (triad asthma or Samter symptoms) syndrome) Treatment Treatment includes allergen avoidance. Intranasal glucocorticoids are first-line therapy. Combination intranasal glucocorticoids and intranasal antihistamine are indicated for severe symptoms. Choose skin testing and allergen immunotherapy if symptoms are not well controlled by intranasal glucocorticoids with supplemental antihistamines or decongestants. The most consistently effective treatments for chronic nonallergic rhinitis are topical intranasal glucocorticoids, topical intra- nasal antihistamines, and topical ipratropium bromide. DO]II,T BE TRICKED . Do not refer patients with allergic rhinitis for skin testing/immunotherapy without a trial of empiric therapy TESTYOURSETF For the past 2 months, a 30 year-old man has had nasal congestion that began with rhinorrhea, coughing, and sore throat. He has used oxymetazoline nasal spray since his symptoms started. ANSWER: For diagnosis, select rhinitis medicamentosa. For management, choose to stop the topical decongestant and select a short course of prednisone or intranasal glucocorticoid. Epistaxis Diagnosis Ninety percent of epistaxis cases originate in the anterior nasal septum. Posterior bleeds are more likely to result in significant hemorrhage. Treatment Anterior bleeds can be managed with compression of the lower one third of the nose. If anterior rhinoscopy can identify the bleeding site, topical vasoconstrictors (e.g., oxymetazoline) and nasal cautery are used for continued bleeding. Posterior bleeds often require nasal packing, cauterization, or arterial ligation or endovascular embolization. 167

General lnternal Medicine Common types of eczematous dermatitis include: . atopic dermatitis o contact dermatitis . hand dermatitis . seborrheicdermatitis Atopic dermatitis is the development of eczema in patients with an inherited atopic diathesis. Look for: e the atopic triad of allergic rhinitis, asthma, and eczema . involvement of the periocular areas and flexural surfaces, including posterior neck, antecubital and popliteal fossae, wrists, and ankles . complicating S. oureus infection evidenced by pustules, crustinS, and erosions Contact dermatitis includes allergic contact dermatitis (type fV hypersensitivity reaction) and irritant contact dermatitis. Allergic contact dermatitis is precipitated by local absorption of an allergen or irritant through the stratum corneum. Causative allergens ("triggers") are identified by epicutaneous patch testing and include: . nickel . topical anesthetics . neomycin and bacitracin . transdermal medication patches . strong soaps, fragrances, or personal care products . rubber . poison oak and poison ivy Irritant contact dermatitis occurs as a direct toxic effect from exposure to a chemical such as a cleaning agent or other caustic substance. Hand dermatitis often results from excessive hand washing, contact dermatitis, atopic dermatitis, or dyshidrotic eczema. It is characterized by pruritic, erythematous plaques on the palmar and dorsal hands, which can lead to fissuring and lichenifica- tion. Dyshidrotic eczema presents with vesicles on the palms and sides of the fingers. Seborrheic dermatitis is an inflammatory scaling, itchy dermatosis that most commonly affects the scalp but can also involve the eyebrows, nasolabial folds, chin, central chest, and perineum. Explosive onset with wide distribution may be a sign of HIV infection. It is commonly seen in patients with Parkinson disease. TESTYOURSELF A 2S-year-old man is evaluated for severe seborrheic dermatitis of acute onset. ANSWER: For evaluation, order HIV testing. DOil'T BETRTGKED . Neomycin and bacitracin, commonly used for wound care, can cause an allergic contact dermatitis that mimics a wound infection. 170

General lnternal Medicine Contact Dermatitis: Discretely grouped red vesicles and bullae in a linear distri- Atopi( Dermatitis: Atopic eczema involves the antecubital fossae, with lichenifica bution are characteristic of contact dermatitis caused by poison ivy. tion and surrounding excoriations. Treatment Atopic dermatitis: . fragrance free synthetic detergents rather than soap o moisturizers o topical glucocorticoids . topical calcineurin inhibitors (tacrolimus and pimecrolimus) as steroid sparing agents (face and skin folds) For irritant hand dermatitis, treat by washing less and moisturizing with emollients. A potent topical glucocorticoid may be necessary during flares (see following). Contact dermatitis: o topical glucocorticoids . 2 to 3 week taper of systemic glucocorticoids for severe reactions Hand dermatitis: . topical emollients (petrolatum) o potent topical glucocorticoid o minimizing excessive or habitual hand washing Seborrheic dermatitis: . selenium sulfide or zinc pyrithione shampoos Seborrheir Dermatitis: Seborrheic dermatitis is shown, with fine, oily scale . ketoconazole shampoo (not oral ketoconazole) around the medial eyebrows. DOT{'T BE TRICKED . Do not select potent glucocorticoids for the face because ofthe risk ofsteroid induced acne and cutaneous atrophy ?ESTYOURSELF A healthy 40-year-old nurse has a 1 month history of vesicular eruptions on the dorsum and distal areas of her hands. ANSWER: For diagnosis, choose acute eczema, likely secondary to latex gloves. For treatment, select a topical glucocorticoid and latex product avoidance. 171

General lnternal Medicine Fixed Drug Eruption: Discrete round to oval lesions are Drug-lnduted Hypersensitilrity Syndrome: Acute facial edema in a patient with characteristic oI a fixed drug eruption. anticonvulsanlinduced hypersensitivity syndrome. Morbilliform Drug Eruption: Morbilliform drug eruption consisting of symmet- rically ananged erythematous macules and papules-some discrete and others loxir Epidermal ltlecrolysis: Shedding of entire sheets ol skin is characteristic of conflu ent. TEN. 174

General lnternal Medicine Treatment STUDY TABLE: Drug Therapy for Acne lndication Mild noninflammatory acne (comedones) Comedolytic agent (topical retinoid such as tretinoin, adapalene, and tazarotene) Mild inflammatory acne (papules and pustules) Topical retinoid and topical antibiotic (erythromycin or clindamycin) Moderate noninflammatory acne Topical retinoid and benzoyl peroxide or azelaic acid Moderate to severe inflammatory acne Topical retinoid, topical antibiotic, and an oral antibiotic (tetracycline or others) Acne in women with hyperandrogenism Oral contraceptive Severe recalcitrant nodular acne Oral isotretinoin (women require two forms of birth control when taking this drug because it is teratogenic) latrogenic perioral acne Discontinue topical glucocorticoid All topical retinoids and oral isotretinoin are contraindicated in pregnancy. Topical clindamycin, azelaic acid, and erythromycin are safe in pregnancy. Treatment of erythrotelangiectatic rosacea focuses primarily on behavioral modifications, such as avoidance of identified trig gers of flushing, proper use of sun protection, and use of gentle skin cleansers. Treatment for papulopustular rosacea includes topical metronidazole, an azelaic acid fbrmulation, and topical ivermectin. Topical glucocorticoids should be avoided. DOil'T BE TRICKED o Avoid oral or topical antibiotic monotherapy for treatment of moderate to severe acne because of increased antibiotic resistance; combine with topical benzoyl peroxide. TESTYOURSETF An l8-year-old man has had nodular and cystic acne. Pustules and nodules with scarring are present on the chin, face, back, and chest. ANSWER: For diagnosis, choose severe inflammatory acne. For treatment, select isotretinoin. Pemphigus Vulgaris and Pemphigoid Diagnosis Pemphigus vulgaris often presents initially as painful, nonhealing oral erosions. Also look for flaccid, hemorrhagic, or seropu rulent bullae and denuded areas that ooze serous fluid, bleed, or are covered with crusts. The esophagus and vulva may also be involved. Look for a positive Nikolsky sign (erosion of normal appearing skin by application of sliding pressure).

Pemphigus Vulgaris and Pemphigoid Diagnosis Pemphigus vulgaris often presents initially as painful, nonhealing oral erosions. Also look for flaccid, hemorrhagic, or seropu rulent bullae and denuded areas that ooze serous fluid, bleed, or are covered with crusts. The esophagus and vulva may also be involved. Look for a positive Nikolsky sign (erosion of normal appearing skin by application of sliding pressure). SfUEY TABLE: Differential Diagnosis of Blisters Condition Key Features Pemphigus Flaccid blisters that rapidly transform to large, weeping, denuded areas and appear most commonly on the oral vulgaris mucosa, trunk, and proximal extremities. Only erosions may be clinically apparent. Nikolsky sign is positive. Direct immunofluorescence shows intercellular lgG deposition. Bullous Tense blisters most commonly seen in older adults on the trunk, limbs, and flexures. Oral lesions are uncommon. pemphigoid Nikolsky sign is negative. Direct immunofluorescence shows linear lgG deposition at the basement membrane. 176

General lnternal Medicine Bullous Pemphigoid: An autoimmune blistering disease characterized by multi ple tense bullae and occasional erosions; mucosal surfaces are typically not Pemphigus: Ihis patient has multiple erosions and crusting with only an occa involved. sional intact blister; mucosal surfaces are typically involved. DON'T BE TRICKED o The blisters ofpemphigus vulgaris are so fragile that they are rarely seen; look instead for erosions, crusting, and sores in the mouth. Treatment Oral glucocorticoids are first line therapy for pemphigus'",ulgaris and pemphigoid. Patients who do not respond to conventional drug treatment may require plasmapheresis. TESTYOURSELF A72 year old man has a 1 week history of a rash on his trunk and upper arms. He has lost 5 kg (tt lbs). Oral erosions and bullae are present on his trunk. Pressure applied to the edge ofone ofthe blisters causes it to extend laterally without eruption. ANSWER: Choose pemphigus for diagnosis. Biopsy is required for diagnosis. Dermatophyte and Yeast lnfections Diagnosis Dermatophytes are types of fungi that invade epidermal stratum corneum, hair, and nails, causing tinea infbctions. Yeast infections include Cctndida, the main yeast species infecting humans, and Malassezio, causing pityriasis versicolor. Physical Examination Dermatophytosis causes the following . Acute tinea pedis presents with 1 to 2-mm vesicles and can be extremely pruritic. The interdigital variant of tinea pedis shows fissures and maceration in the folds. r Chronic tinea pedis and tinea manuum present as mildly pruritic, scaly patches involving most of the palms and soles in a "moccasin" or "glove" distribution. "One hand, tvvo feet" is a characteristic pattern of involvement in tinea. 177

General lnternal Medicine o Tinea corporis most typically presents as an annular lesion with an active erythematous border of small vesicles and scales, often with central clearing. o Tinea cruris (jock itch) is a dermatophl,te infection of the inguinal folds presenting as erythematous patches with a rim of scale that does not involve the scrotum. . Onychomycosis is usually characterized by a thickened, yellow or white nail with scaling under the elevated, distal free edge of the nail plate. Sometimes, however, the infecting organism invades the surface of the toenail, presenting as a white crust. Cutaneous candidiasis is characterized by red, itchy, inflamed skin. At sites ofskin to skin contact, lesions have glazed, shiny, and, at times, eroded surfaces. Satellite pustules (yellow, fluid-fi]led lesions at the edge of the confluent red eruption) are a key physical finding. Testing Diagnosis of dermatophy.te infection is made by examination of the scale or subungual debris with KOH demonstrating the pres ence of branching hyphae. Pityriasis (tinea) versicolor is associated with yeast spores charac terized by "spaghetti and meatballs" microscopic appearance. Candida is associated with pseudohyphae and spores.

Testing Diagnosis of dermatophy.te infection is made by examination of the scale or subungual debris with KOH demonstrating the pres ence of branching hyphae. Pityriasis (tinea) versicolor is associated with yeast spores charac terized by "spaghetti and meatballs" microscopic appearance. Candida is associated with pseudohyphae and spores. DOI{'T BE TRICKED ., . :. . . . Tinea cruris spares the scrotum, whereas intertrigo does '' ^ -.. , . . .-,,. ,. " not. Pityriasis Versirolor KOH: Hyphae and yeast cells are recognized as a "spaghetti . Two feet-one hand tinea is a common presentation of un j1-n.utballs,, pattern. tinea pedis. o Nail dystrophy may be caused by psoriasis, aging, or peripheral vascular disease and mimics onychomycosis. Tinea Infection: Tinea most commonly presents Chronit Tinea Pedis: Extension of tinea pedis onto the sole and sides of the foot as a round or oval erythematous scaling patch that ("moccasin" appearance) presents as chronic scaling. spreads centrifugally with central clearing. lt has an active border that is raised, consisting of tiny pap. ules or vesicles and scale. 178

General lnternal Medicine \ Candida lnfection: Bright red papules, vesicles, pustules, and patches with satel 0nychomycosis: Distal subungual thickening and nail separation (white areas of lite papules and pustules are characteristic o{ candidiasis. nail) involving most of the nails are associated with onychomycosis. Treatment STUDY TABLE: Treatment for Dermatophyte and Yeast lnfections Indication Treatment Most dermatophyte infections except tinea capitis and Topicalterbinafine or imidazole creams, such as miconazole, onychomycosis clotrimazole, and ketoconazole Confirmed onychomycosis, tinea capitis, extensive tinea corporis, Oral terbinafine or itraconazole treatment-resistant dermatophytosis lnitial treatment of pityriasis versicolor Topical ketoconazole, selenium sulfide Recu rrent pityriasis versicolor Itraconazole or fluconazole, single dose Candida infections Topical nystatin, miconazole, clotrimazole, ketoconazole, econazole Treatment of onychomycosis is typically not necessary but is recommended for patients with peripheral vascular disease or diabetes to prevent the development of cellulitis. DON'T BE TRICKED . Do not select antifungal treatment for thick, yellow, and crumbling toenails without KOH scraping or positive culture for dermatophytes. . Never select a combination of a topical antifungal agent and a glucocorticoid for treatment of an unknown skin rash or dermatophyte infection. o Do not choose oral ketoconazole as initial antifungal treatment because of the risk ofsevere hepatotoxicity.

DON'T BE TRICKED . Do not select antifungal treatment for thick, yellow, and crumbling toenails without KOH scraping or positive culture for dermatophytes. . Never select a combination of a topical antifungal agent and a glucocorticoid for treatment of an unknown skin rash or dermatophyte infection. o Do not choose oral ketoconazole as initial antifungal treatment because of the risk ofsevere hepatotoxicity. TESTYOURSELF A 35 year old man has a nonpruritic rash on his chest. He previously had a similar rash that became hypopigmented when he became suntanned. ANSWER: For clinical diagnosis, choose pityriasis versicolor. For management, order KOH preparation of the scale with demonstration of a "spaghetti and meatballs" hyphae pattern. Pityriasis Versicolor: Hypopigmented, scaly macules are present on the chest. 179

General lnternal Medicine l. Scabies Rash: Multiple pink to red, glistening papules and erosi0ns with diffuse n scaling, predominately in the finger webs, characteristic of scabies. Scabies: Sarcoptes scabiei, the organism responsible for scabies, is shown after K0H preparation {rom skin scraping. TESTYOURSETF A 67-year old woman with a recent hospitalization and her 3-year old granddaughter have a 3-week history of generalized pruri- tus. Both patients have widespread excoriations and interdigital linear burrows. ANSWER: For diagnosis, select scabies. For treatment, choose topical permethrin for patients and other close contacts. Bedbugs Diagnosis Classic presentation is grouped, itchy papules in close configuration ("breakfast, lunch, and dinner") on exposed body areas. Bites are typically noticed in the morning because bedbugs feed at night. Treatment Lesions will resolve spontaneously. Symptomatic treatment involves topical glucocorti coids and orul antihistumines. Eradication ofthe bedbug is necessary fbr a "cure." Bedbugs: Classic grouped pruritic papules ("breakfast, lunch, and dinner") presentation of Seborrheic Keratosis bites from bedbugs Diagnosis Seborrheic keratosis is a painless, nonmalignant growth that appears as a "stuck on" waxy, brownish patch (color ranges from tan to black) or plaque. It can be found anyr,vhere on the body except the palms, soles, and mucous membranes. 182

l l I General lnternal Medicine t Dysplastic nevi are markers for an increased risk of melanoma. Autosomal-dominant familial melanoma/dysplastic nevus syn- drome is defined by the presence of melanoma in at least two relatives; more than 50 nevi, with multiple nevi having atypical clinical and histologic features; and dysplastic nevi in other family members. Treatment Dysplastic nevi that develop increased characteristics associated with melanoma (fuzzy or ill-defined borders, multiple colors, diameter 25 mm), have otherwise changed, or stand out from other nevi must be removed and sent for patholory. Actinic Keratosis Diagnosis Lesions are located on sun-exposed sites and appear as 2- to Dysplastit llevi: Dysplastic nevi share similar characteristics 3-mm, elevated, flesh-colored or red papules with adherent, with melanoma including asymmetry, indistinct and inegular borders, and variation in pigmentation. whitish scale or "rough spots" that may be easier to palpate than visualize. Actinic keratosis is a precursor to SCC. Treatment Destruction by liquid nitrogen or curettage is the preferred treatment for most single lesions. Topical S-FU or imiquimod cream is used for the treatment of numerous lesions. Squamous Cell Carcinoma Actinic l(entoses: Mu ltiple white, scaly patches measu ring l-3 mm on the hands are characteristic of actinic keratoses. Diagnosis SCC presents as a slowly evolving, isolated, keratotic, or eroded macule, papule, or nodule that commonly appears on the scalp, neck, pinna, or lip. Bowen disease is a form of anaplastic in situ SCC that presents as circumscribed erythematous or pigmented patches that typically have a keratotic surface. Shave biopsy conlirms the diagnosis ofSCC. Keratoacanthoma is a form of SCC generally appearing as a rapidly growing pink nodule with a prominent central plug of scale and crust; its appearance is "volcaniform," resembling the cinder cone of a volcano. 184

General lnternal Medicine l(eratoaonthoma: A form of SCC that appears as a rapidly growing, pink, 'vol- Cutaneous Squamous Cell Carcinoma: Typically presents as a slowly evolving, caniform" nodule with a prominent central plug of scale and crust. isolated, keratotic, or eroded macule, papule, or nodule that commonly appears on the scalp, neck, pinna, or lip. Treatment Small lesions can be treated with electrodesiccation and curettage. Most lesions require excision. Basal Cell Carcinoma Diagnosis The most characteristic lesion is a pink, pearly, translucent papule or nodule with telangiectasias, rolled borders, and central depression with ulceration. Superficial BCCs are well-demarcated, irregularly bordered, red patches; they tend to enlarge radially rather than invading into deeper structures. Biopsy should be performed for clinically suspicious lesions. Treatment Most BCCs are treated with simple excision. Ill-defined lesions, high-risk histologic types, and tumors on the face and hands are often best treated with Mohs micrographic surgery. Basal Cell Gnlnoma: Ihis pink, pearly, translucent, domeshaped papule with telangiectasias is characteris' tic ol BCC. 185

General lnternal Medicine Treatment Smoking cessation is recommended for all patients; smoking worsens psoriasis, and CAD is common among patients with psoriasis. Patients with localized disease: . topical glucocorticoids for limited, localized plaques . topical vitamin D analogues as monotherapy or in combination with topical glucocorticoids Patients with skin involvement of greater than 10",1, body surface area, psoriatic arthritis, or psoriasis recalcitrant to topical treat ments should receive: . phototherapy . methotrexate, acitretin, or cyclosporine Patients receiving systemic glucocorticoids or cyclosporine are at risk for acute er).throdermic or pustular flares with sudden cessation of medication. Erythroderma is a dermatologic emergency because patients are at high risk for infection as well as electrolyte abnormalities secondary to fluid loss. Guftate Psoriasis: Note the characteristic lesions consisting of multiple, discrete, drop-like papules with a salmon-pink hue. A fine scale, which is usually absenl in I{ail Findings in Psoriasis: Psoriatic nails are shown, with characteristic discol, early-stage lesions, may be observed on more established lesions. lmage reprinted oration, crumbling, subungual debris, and separation ofthe nail plate Irom the nail with permission from Hon 5. Pak, MD, FAAD,3M Health lnformation Systems, pub. bed (white areas of nail). lished by Medscape Drugs & Diseases (http://emedicine.medscape.com/), Guttate Psoriasis, 2017, available at: https://emedicine.medscape.com/article/1 107850. ove rview. lnverse Psoriasis: lnverse psoriasis presents as a bright red, smooth patch in the Chronic Plaque Psoriasis: The image depicts classic plaque psoriasis, showing folds of the skin, typically occurring under the breasts, in the armpits, near the erythematous plaques with a silvery scale on an extensor surface. genitals, under the buttocks, or in abdominal folds. 188

General lnternal Medicine I nvoluntary Weight Loss Diagnosis Causes of involuntary weight loss vary according to age (malignancy is most common in the young) and venue (depression, medications, dehydration, and issues related to dementia are most common in extended care facilities). Weight loss is commonly associated with depression and dementia. Socioeconomic and functional problems, such as difficulty obtaining food, lack of financial resources, and social isolation, cause or exacerbate weight loss. Initial diagnostic testing is limited to basic studies (such as TSH level, HIV testing, age-appropriate cancer screening) unless the history and physical examination suggest a specific cause. DON'T BE TRICKED . Imaging of the thorax and abdomen with CT or MRI in the absence of supporting history, physical examination, or laboratory findings is not helpful. Treatment Treat the specific underlying disorder. The proven benefit of oral nutritional supplementation for weight loss is limited. Appetite stimulants have been shown to promote weight gain, but a survival benefit has never been demonstrated.

DON'T BE TRICKED . Imaging of the thorax and abdomen with CT or MRI in the absence of supporting history, physical examination, or laboratory findings is not helpful. Treatment Treat the specific underlying disorder. The proven benefit of oral nutritional supplementation for weight loss is limited. Appetite stimulants have been shown to promote weight gain, but a survival benefit has never been demonstrated. STUDY TABLE: Selected Nutritional Deficiencies Finding Deficiency Petechiae, perifollicular hemorrhage, gingival bleeding Vitamin C Ecchymosis Vitamins C and K Skin pigmentation, cracking, and crusting Niacin Acro-orificial dermatitis (erythematous, vesiculobullous, and pustular) Zinc Angular stomatitis and cheilosis Vitamin B complex, iron, and protein Glossitis Niacin and vitamin 812 Ophthalmoplegia and foot drop Thiamine Pa resthesia Thiamine, folate, and vitamin B12 Depressed vibratory and position senses Vitamin 812 Memory disturbance Vitamin 812 Wernicke-Korsakoff syndrome Severe thiamine deficiency Night blindness Vitamin A Osteomalacia Vitamin D Depression Vitamin C 190

I L I I I I L I I Hematology L t I L i t Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria I I Diagnosis Aplastic anemia is a disorder in which hematopoietic stem cells are severely diminished, resulting in hypocellular bone marrow and pancytopenia. All cell lines are involved. Autoimmune attack on stem cells is the most common identifiable cause. Other causes include toxins, ionizing radiation, drugs, nutritional deftciencies, and infections. PNH results from a genetic mutation of membrane proteins that ameliorate complement-mediated destruction of erythrocytes. PNII can be isolated or associated with MDS and aplastic anemia. PNH is characterized by: . chronic intravascular hemolytic anemia . iron deficiency through urinary losses o arterial and venous thrombosis (including Budd-Chiari syndrome) t*. { o pancytopenia Testing I 1 The basic evaluation of patients presenting with pancytopenia includes: { . bone marrow aspirate and biopsy (hypocellular with ,l 1.n .t 'a increased fat content) 1P . c,4ogenetic analysis to exclude other bone marow disorders { (e.g., MDS) J'I

Testing I 1 The basic evaluation of patients presenting with pancytopenia includes: { . bone marrow aspirate and biopsy (hypocellular with ,l 1.n .t 'a increased fat content) 1P . c,4ogenetic analysis to exclude other bone marow disorders { (e.g., MDS) J'I . PNH screening flow cltometry with absent CD55 and CD59 { cell surface markers I '.\ a { o vitamin Bu and folate levels, hepatitis serologies, and HIV AplasticAnemia: Profoundly hypocellular bone marrow is characteristic, with the testing marrow space composed mostly of fat cells and malrow stroma. Treatment Initial treatment of aplastic anemia involves withdrawal of any potentially causative agents. Allogeneic HSCT is a potentially curative therapy and should be considered for those younger than 50 years who have a suitable match. Immunosuppression with cyclosporine and antithymocyte globulin is also effective first-line therapy and leads to disease control in 7Oo/,, of adult patients.

Treatment Initial treatment of aplastic anemia involves withdrawal of any potentially causative agents. Allogeneic HSCT is a potentially curative therapy and should be considered for those younger than 50 years who have a suitable match. Immunosuppression with cyclosporine and antithymocyte globulin is also effective first-line therapy and leads to disease control in 7Oo/,, of adult patients. In symptomatic patients with PNH, eculizumab or ravulizumab reduces intravascular hemolysis, hemoglobinuria, and the need for transfusion. Patients should receive meningococcal vaccination before use because of an increased risk of Neisserio infections. Allogeneic HSCT can lead to long term survival. Prophylactic anticoagulation and supplementation with iron and folic acid are indicated in all patients. 191