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Sjtigren Syndrome demonstration of autoimmunity (Table 23 shows validated enlargement. Sarcoidosis, IgG4 related disease, granulomato classification criteria). Ophthalmic dryness can be assessed sis with polyangiitis, lymphoma, and infection (such as by using the Schirmer test, in which a strip of filter paper is mumps, hepatitis C virus infection, and HIV infection) may be placed under the lower eyelid and wetting is measured; less associated with similar findings. Ocular and oral dryness may than 5 mm of wetting in 5 minutes indicates dryness. More also occur with aging, in other disease states (such as rheuma- formally, dryness and corneal damage are ascertained with toid arthritis), or as an adverse effect of medications or treat slit lamp examination by an ophthalmologist. Topical stain- ment (such as antidepressants and antihistamines or radiation ing may be used to identiff injury and fissures in the cornea. of the head and neck). Unilateral or single enlargement of a Dry mouth is assessed by direct examination, with dental gland should raise concern for obstruction or malignancy. caries and a lack of saliva suggesting the diagnosis. Measurement of salivary flow, or sialometry should ideally be performed to determine whether true dryness is present (and Management to show ductal architecture). However, this is rarely done Management of sicca centers on preserving moisture and because it requires special equipment that is not available in relieving symptoms. Eye dryness is treated with over the most settings. Other forms of imaging (e.g., CT, gallium scan counter artificial tears, gels, and ointmentsi lor refractory or ning) are not generally helpful but may rarely be useful in more severe symptoms, topical cyclosporine or a small defining organ involvement. molecule integrin antagonist may be added. Plugging the lac- Multiple autoantibodies may be found in Sjdgren syn- rimal ducts to promote tear retention is widely performed, but drome, but none are independently diagnostic. Antinuclear clinical trials have not shown its effectiveness. For oral antibodies and/or rheumatoid factor are often present at high dryness, first-line treatment in patients with less severe titers; their coexpression is more suggestive of Sjogren s1m- symptoms should be nonpharmacologic salivary stimulation, drome than is positivity of only one. The presence of anti-Ro/ both with gustatory stimulants (e.g., sugar-free candy) and SSA autoantibodies is specific in primary Sjdgren syndrome mechanical stimulants (e.g., sugar-free gum). but less so in secondary Sjdgren syndrome because these anti Pharmacologic therapies should be reserved for moder bodies are also common in systemic lupus erythematosus. ate or severe oral dryness. These include the muscarinic Anti LalSSB autoantibodies are characteristic ofSjogren syn- agonists pilocarpine and cevimeline, which may not be well drome but are not included in formal classification criteria. tolerated; they are also contraindicated in narrow-angle When initial evaluation is uninformative, a lip (minor salivary glaucoma. Artificial saliva may be used for severe dysfunc gland) biopsy should be considered. Characteristic histologic tion, but its effects are so transient that most patients do not features include aggregate foci (>50 cells/aggregate) of CD4 T find it useful. Meticulous dental care is essential to prevent cells, B cells, and plasma cells surrounding secretory ducts. gingivitis and dental decay, regardless of symptom severity. The differential diagnosis of SjOgren syndrome tlpically Vaginal symptoms may be treated with topical lubricants or relates to the presence of sicca and/or parotid and lacrimal estrogen. Active extraglandular autoimmune disease should be TABLE 23. American College of Rheumatology/European treated with systemic therapies. In most cases, glucocorticoids League Against Rheumatism Classification Criteria for may be considered as a first line option, but only at the Primary Sjogren Syndrome" minimum dose and length of time necessary to control the Presence of subjective finding of Sjtigren syndrome active disease. Immunomodulatory/immunosuppressive (e.g., (e.9., sicca) plus any combination of the following hydroxychloroquine, methotrexate, cyclophosphamide) and resulting in a score of >4: biologic (e.9., anti-B cell therapy with rituximab or beli- Item Score mumab) agents should be considered for second or third line Salivary gland biopsy specimen showing )1 foci of 2 therapy, or for glucocorticoid sparing. To the extent possible, lymphocytic infiltrate/4 mm2 decisions should be tailored to severity and the organ or organs Anti- Ro/SSA autoa ntibodies 3 affected (e.9., pneumonitis, central nervous system disease). Ocular staining score >5 in at least one eye Musculoskeletal pain is common in Sjogren syndrome but Schirmertest<5 mm/5 min in at least one eye should not be treated with immunomodulatory or biologic Unstimulated whole saliva flow rate <0.1 mUmin therapy unless there is objective evidence of active inflamma- tory arthritis. Myalgia and arthralgia, along with chronic non nExclusion criteria include prior head/neck radiation and history of active hepatitis C virus infection, AIDS, sarcoidosis, amyloidosis, graft-versus host disease, and specific pain, should be treated symptomatically. lgG4 related d sease.

demonstration of autoimmunity (Table 23 shows validated enlargement. Sarcoidosis, IgG4 related disease, granulomato classification criteria). Ophthalmic dryness can be assessed sis with polyangiitis, lymphoma, and infection (such as by using the Schirmer test, in which a strip of filter paper is mumps, hepatitis C virus infection, and HIV infection) may be placed under the lower eyelid and wetting is measured; less associated with similar findings. Ocular and oral dryness may than 5 mm of wetting in 5 minutes indicates dryness. More also occur with aging, in other disease states (such as rheuma- formally, dryness and corneal damage are ascertained with toid arthritis), or as an adverse effect of medications or treat slit lamp examination by an ophthalmologist. Topical stain- ment (such as antidepressants and antihistamines or radiation ing may be used to identiff injury and fissures in the cornea. of the head and neck). Unilateral or single enlargement of a Dry mouth is assessed by direct examination, with dental gland should raise concern for obstruction or malignancy. caries and a lack of saliva suggesting the diagnosis. Measurement of salivary flow, or sialometry should ideally be performed to determine whether true dryness is present (and Management to show ductal architecture). However, this is rarely done Management of sicca centers on preserving moisture and because it requires special equipment that is not available in relieving symptoms. Eye dryness is treated with over the most settings. Other forms of imaging (e.g., CT, gallium scan counter artificial tears, gels, and ointmentsi lor refractory or ning) are not generally helpful but may rarely be useful in more severe symptoms, topical cyclosporine or a small defining organ involvement. molecule integrin antagonist may be added. Plugging the lac- Multiple autoantibodies may be found in Sjdgren syn- rimal ducts to promote tear retention is widely performed, but drome, but none are independently diagnostic. Antinuclear clinical trials have not shown its effectiveness. For oral antibodies and/or rheumatoid factor are often present at high dryness, first-line treatment in patients with less severe titers; their coexpression is more suggestive of Sjogren s1m- symptoms should be nonpharmacologic salivary stimulation, drome than is positivity of only one. The presence of anti-Ro/ both with gustatory stimulants (e.g., sugar-free candy) and SSA autoantibodies is specific in primary Sjdgren syndrome mechanical stimulants (e.g., sugar-free gum). but less so in secondary Sjdgren syndrome because these anti Pharmacologic therapies should be reserved for moder bodies are also common in systemic lupus erythematosus. ate or severe oral dryness. These include the muscarinic Anti LalSSB autoantibodies are characteristic ofSjogren syn- agonists pilocarpine and cevimeline, which may not be well drome but are not included in formal classification criteria. tolerated; they are also contraindicated in narrow-angle When initial evaluation is uninformative, a lip (minor salivary glaucoma. Artificial saliva may be used for severe dysfunc gland) biopsy should be considered. Characteristic histologic tion, but its effects are so transient that most patients do not features include aggregate foci (>50 cells/aggregate) of CD4 T find it useful. Meticulous dental care is essential to prevent cells, B cells, and plasma cells surrounding secretory ducts. gingivitis and dental decay, regardless of symptom severity. The differential diagnosis of SjOgren syndrome tlpically Vaginal symptoms may be treated with topical lubricants or relates to the presence of sicca and/or parotid and lacrimal estrogen. Active extraglandular autoimmune disease should be TABLE 23. American College of Rheumatology/European treated with systemic therapies. In most cases, glucocorticoids League Against Rheumatism Classification Criteria for may be considered as a first line option, but only at the Primary Sjogren Syndrome" minimum dose and length of time necessary to control the Presence of subjective finding of Sjtigren syndrome active disease. Immunomodulatory/immunosuppressive (e.g., (e.9., sicca) plus any combination of the following hydroxychloroquine, methotrexate, cyclophosphamide) and resulting in a score of >4: biologic (e.9., anti-B cell therapy with rituximab or beli- Item Score mumab) agents should be considered for second or third line Salivary gland biopsy specimen showing )1 foci of 2 therapy, or for glucocorticoid sparing. To the extent possible, lymphocytic infiltrate/4 mm2 decisions should be tailored to severity and the organ or organs Anti- Ro/SSA autoa ntibodies 3 affected (e.9., pneumonitis, central nervous system disease). Ocular staining score >5 in at least one eye Musculoskeletal pain is common in Sjogren syndrome but Schirmertest<5 mm/5 min in at least one eye should not be treated with immunomodulatory or biologic Unstimulated whole saliva flow rate <0.1 mUmin therapy unless there is objective evidence of active inflamma- tory arthritis. Myalgia and arthralgia, along with chronic non nExclusion criteria include prior head/neck radiation and history of active hepatitis C virus infection, AIDS, sarcoidosis, amyloidosis, graft-versus host disease, and specific pain, should be treated symptomatically. lgG4 related d sease. From Shiboski CH, Shib,oski SC, Seror R, et al; lnternational Sjogren's Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjogren's Prognosis Syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 201 7 Jan;69(1 ):35-45. The prognosis for primary Sj6gren syndrome is favorable, with doi:1 0.1 002/art.39859. IPMID: 27785888]. Copyright 201 6, American College of no overall increase in mortality. Management of sicca reduces Rheumatology. Adapted with permission from John Wiley & Sons, lnc. the risk for corneal damage or tooth loss. In rare instances,

From Shiboski CH, Shib,oski SC, Seror R, et al; lnternational Sjogren's Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjogren's Prognosis Syndrome: a consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 201 7 Jan;69(1 ):35-45. The prognosis for primary Sj6gren syndrome is favorable, with doi:1 0.1 002/art.39859. IPMID: 27785888]. Copyright 201 6, American College of no overall increase in mortality. Management of sicca reduces Rheumatology. Adapted with permission from John Wiley & Sons, lnc. the risk for corneal damage or tooth loss. In rare instances, 52

ldiopathic lnflammatory Myopathies end-organ involvement can be life threatening. Secondary Sj6gren syndrome may be associated with significant morbid- Evaluation of the Patient With ity from the primary condition. Muscle Pain or Weakness The differential diagnosis of muscle disease is broad and rEY POITII includes hereditary environmental, infectious, and acquired o Sjdgren syndrome is an autoimmune exocrinopathy conditions (Table 2a). The IIMs commonly present with sym affecting salivary and lacrimal glands; the most com metric proximal muscle weakness without substantial muscle mon presentation is sicca (dryness of the eyes and/or pain or tenderness. Serum creatine kinase levels are almost mouth). universally elevated, and this elevation is a marker of muscle o Patients with Sjdgren syndrome are at increased risk for damage. The presence of pain or tenderness should prompt non-Hodgkin lymphoma. consideration of alternative causes, such as infectious, endo- . A diagnosis of Sjogren syndrome is lzpically triggered crine (thyroid), or drug induced myopathies. Medications and by the patient's report ofocular and oral dryness and drugs are common causes of muscle pain and weakness and requires objective confirmation of exocrinopathy, along should also be considered in the differential diagnosis ofthe with demonstration of autoimmunity inflammatory myopathies (Table 2S). Muscle weakness must be differentiated from general . In patients with Sjogren syndrome, management of ized weakness, which is common and caused by conditions sicca centers on preserving moisture and relieving such as cardiopulmonary disease, malignancy, depression, symptoms; extraglandular involvement is treated with and deconditioning. Primary neurologic disorders (e.g., immunosuppression. spinal muscle atrophies, amyotrophic lateral sclerosis, and myasthenia gravis) may cause muscle weakness but are dis tinguished by involvement of nonproximal muscle groups and nerve involvement on electromyography; an elevated ldiopathic lnflammatory serum creatine kinase level is uncommon. Exercise-induced Myopathies weakness may point to a metabolic or mitochondrial cause rather than an IIM. Overview Idiopathic infl ammatory myopathies (llMs) are characterized by muscle inflammation and proximal muscle weakness. Epidemiology and Subcategories in adult patients include polymyositis, dermato Pathophysiology myositis, immune mediated necrotizing myopathy, and inclu IIMs are uncommon and heterogeneous. The annual incidence sion body myositis. is between 2 and 10 cases per million. Two peaks of onset

end-organ involvement can be life threatening. Secondary Sj6gren syndrome may be associated with significant morbid- Evaluation of the Patient With ity from the primary condition. Muscle Pain or Weakness The differential diagnosis of muscle disease is broad and rEY POITII includes hereditary environmental, infectious, and acquired o Sjdgren syndrome is an autoimmune exocrinopathy conditions (Table 2a). The IIMs commonly present with sym affecting salivary and lacrimal glands; the most com metric proximal muscle weakness without substantial muscle mon presentation is sicca (dryness of the eyes and/or pain or tenderness. Serum creatine kinase levels are almost mouth). universally elevated, and this elevation is a marker of muscle o Patients with Sjdgren syndrome are at increased risk for damage. The presence of pain or tenderness should prompt non-Hodgkin lymphoma. consideration of alternative causes, such as infectious, endo- . A diagnosis of Sjogren syndrome is lzpically triggered crine (thyroid), or drug induced myopathies. Medications and by the patient's report ofocular and oral dryness and drugs are common causes of muscle pain and weakness and requires objective confirmation of exocrinopathy, along should also be considered in the differential diagnosis ofthe with demonstration of autoimmunity inflammatory myopathies (Table 2S). Muscle weakness must be differentiated from general . In patients with Sjogren syndrome, management of ized weakness, which is common and caused by conditions sicca centers on preserving moisture and relieving such as cardiopulmonary disease, malignancy, depression, symptoms; extraglandular involvement is treated with and deconditioning. Primary neurologic disorders (e.g., immunosuppression. spinal muscle atrophies, amyotrophic lateral sclerosis, and myasthenia gravis) may cause muscle weakness but are dis tinguished by involvement of nonproximal muscle groups and nerve involvement on electromyography; an elevated ldiopathic lnflammatory serum creatine kinase level is uncommon. Exercise-induced Myopathies weakness may point to a metabolic or mitochondrial cause rather than an IIM. Overview Idiopathic infl ammatory myopathies (llMs) are characterized by muscle inflammation and proximal muscle weakness. Epidemiology and Subcategories in adult patients include polymyositis, dermato Pathophysiology myositis, immune mediated necrotizing myopathy, and inclu IIMs are uncommon and heterogeneous. The annual incidence sion body myositis. is between 2 and 10 cases per million. Two peaks of onset TABLE 24. Differential Diagnosis of Myopathy Myopathy Common Examples Comments ldiopathic inflammatory Dermatomyositis; polymyositis; immune-mediated Dermatomyositis and polymyositis: acute-subacute myopathies necrotizing myopathy; inclusion body myositis onset, symmetric, proximal Dermatomyositis: pathognomonic rash lmmune-mediated necrotizing myopathy: acute onset, symmetric, proximal lnclusion body myositis: insidious onset, proximal and distal Systemic rheumatologic Systemic lupus erythematosus; systemic sclerosis; Prominent extramuscular features typical of disease mixed connective tissue disease underlying disorder Muscular dystrophies Duchenne muscular dystrophy; Becker muscular Childhood onset; cardiomyopathy possible dystrophy Metabolic myopathies Glycogen storage diseases; carnitine Exercise intolerance pal mitoyltra nsferase deficiency

TABLE 24. Differential Diagnosis of Myopathy Myopathy Common Examples Comments ldiopathic inflammatory Dermatomyositis; polymyositis; immune-mediated Dermatomyositis and polymyositis: acute-subacute myopathies necrotizing myopathy; inclusion body myositis onset, symmetric, proximal Dermatomyositis: pathognomonic rash lmmune-mediated necrotizing myopathy: acute onset, symmetric, proximal lnclusion body myositis: insidious onset, proximal and distal Systemic rheumatologic Systemic lupus erythematosus; systemic sclerosis; Prominent extramuscular features typical of disease mixed connective tissue disease underlying disorder Muscular dystrophies Duchenne muscular dystrophy; Becker muscular Childhood onset; cardiomyopathy possible dystrophy Metabolic myopathies Glycogen storage diseases; carnitine Exercise intolerance pal mitoyltra nsferase deficiency Mitochondrial myopathies Kearns-Sayre syndrome; Leigh syndrome Variable age of presentation and features; isolated myopathy or with neurologic, multisystem disease Endocrine disorders Hypothyroidism; hyperthyroidism; adrena I Prominent myalgia insufficiency Infection-ind uced Bacterial: pyomyositis; viral: influenza; parasitic Prominent myalgia; sometimes accompanied by trichinosis fever 53

ldiopathic lnflammatory Myopathies TABLE 25. Drug-lnduced MyoPathies Drug Time Course Clinical Presentation Alcohol lncreased with long-term use Asymptomatic elevations of serum creatine kinase; chionic muscle atrophy; acute, severe rhabdomyolysis with kidney failure Antimalarials Can occur after prolonged use lnfrequent elevation of serum creatine kinase (30%); muscle weakness (50%); myopathic electromyog ram findings (100%); cardiomyopathy can occur Cocaine Can occur after single use Asymptomatic elevations of serum creatine kinase; acute, severe rhabdomyolysis with kidney failure Colchicine Usually months to years; increased risk with Proximal muscle weakness with elevations of serum coad ministration of cytochrome P450 inhibitors creatine kinase; mild sensory symptoms; reduced reflexes

TABLE 25. Drug-lnduced MyoPathies Drug Time Course Clinical Presentation Alcohol lncreased with long-term use Asymptomatic elevations of serum creatine kinase; chionic muscle atrophy; acute, severe rhabdomyolysis with kidney failure Antimalarials Can occur after prolonged use lnfrequent elevation of serum creatine kinase (30%); muscle weakness (50%); myopathic electromyog ram findings (100%); cardiomyopathy can occur Cocaine Can occur after single use Asymptomatic elevations of serum creatine kinase; acute, severe rhabdomyolysis with kidney failure Colchicine Usually months to years; increased risk with Proximal muscle weakness with elevations of serum coad ministration of cytochrome P450 inhibitors creatine kinase; mild sensory symptoms; reduced reflexes Glucocorticoids lncreased with long-term use Proximal muscle weakness in the absence of elevations of serum creatine kinase Statins Usually weeks to months but can occur at any time; Elevations of serum creatine kinase with myalgia and increased risk with preexisting neuromuscular disease, weakness hypothyroi d ism, kid n ey fa i I u re, a nd/o r coad m i n istrati o n of cytochrome P450 inhibitors; may also trigger immune- mediated necrotizing myopathy Zidovudine Variable; may be more common after long-term use Elevations of serum creatine kinase with myalgia and weakness

Glucocorticoids lncreased with long-term use Proximal muscle weakness in the absence of elevations of serum creatine kinase Statins Usually weeks to months but can occur at any time; Elevations of serum creatine kinase with myalgia and increased risk with preexisting neuromuscular disease, weakness hypothyroi d ism, kid n ey fa i I u re, a nd/o r coad m i n istrati o n of cytochrome P450 inhibitors; may also trigger immune- mediated necrotizing myopathy Zidovudine Variable; may be more common after long-term use Elevations of serum creatine kinase with myalgia and weakness occur: the first in childhood and the second in middle age. A f,EY POtrtt female adult predominance is approximately 2:1, with the . Inflammatory myopathies commonly present with exception of inclusion body myositis, which preferentially symmetric proximal muscle weakness without substan- affects men. tial muscle pain or tenderness; elevation ofserum cre- Like many other autoimmune diseases, IIMs probably atine kinase level is almost universal and is a marker of result from interactions between genetic and environmental muscle damage. factors. The clearest genetic association is with HLA alleles, o Muscle pain or tenderness should prompt consideration including HLA-DRBI.03:01 with polymyositis and HLA DRB'08:01 with dermatomyositis. Distinct HLA alleles have of infectious, endocrine (thyroid), or drug-induced also been associated with different IIM subgroups, as myopathies. defined by myositis-specific antibodies. However, because HLA associations in IIM vary by ethnic groups around the world, their utility in diagnosis and categorization is Clinical Features limited. Muscle lnvolvement Environmental factors may activate or modify gene Most patients with IIM present with symmetric weakness expression and likely influence disease progression and sever affecting the proximal muscles. Neck flexors and shoulder and ity in addition to onset. Associations with infections, medica- hip girdle muscles are commonly involved. Patients may expe- tions, occupational exposures, ultraviolet light, and other rience difficulty rising from a chair or climbing stairs. factors have been reported. The clearest associations have been Symptoms usually progress over months, except in inclusion with medications, including statins, cytokine-targeted thera body myositis, which progresses over years. Respiratory mus- pies (interferons and tumor necrosis factor inhibitors), and cles can be affected, and some patients experience difficulty checkpoint inhibitors. swallowing (dysphagia or dysmotility) related to involvement Immune mechanisms that contribute to IIM vary of the upper gastrointestinal tract. Cardiac muscle can be between subtypes and include the presence of T- and involved in some subsets of IIM. B-lymphocytic infiltrates, as well as increased cytokine and chemokine levels in muscle tissue. Autoantibodies are Pulmonary Disease expressed in many but not all patients; specific autoantibod Interstitial lung disease, most commonly nonspecific intersti ies and differing histologic patterns are associated with dis tial pneumonitis, occurs in both polymyositis and dermato- tinct sets ofclinical characteristics, suggesting that pathogenic myositis and is an important cause of morbidity and mortaliry mechanisms vary across subsets. Non-immune-mediated particularly in patients the antisynthetase syndrome (see mechanisms are also important, especially for the progres below). Muscle weakness of the chest wall can also cause sion to atrophy, fibrosis, and structural damage to muscle breathing difficulties. Pulmonary involvement is not typically tissue. seen in inclusion body myositis.

occur: the first in childhood and the second in middle age. A f,EY POtrtt female adult predominance is approximately 2:1, with the . Inflammatory myopathies commonly present with exception of inclusion body myositis, which preferentially symmetric proximal muscle weakness without substan- affects men. tial muscle pain or tenderness; elevation ofserum cre- Like many other autoimmune diseases, IIMs probably atine kinase level is almost universal and is a marker of result from interactions between genetic and environmental muscle damage. factors. The clearest genetic association is with HLA alleles, o Muscle pain or tenderness should prompt consideration including HLA-DRBI.03:01 with polymyositis and HLA DRB'08:01 with dermatomyositis. Distinct HLA alleles have of infectious, endocrine (thyroid), or drug-induced also been associated with different IIM subgroups, as myopathies. defined by myositis-specific antibodies. However, because HLA associations in IIM vary by ethnic groups around the world, their utility in diagnosis and categorization is Clinical Features limited. Muscle lnvolvement Environmental factors may activate or modify gene Most patients with IIM present with symmetric weakness expression and likely influence disease progression and sever affecting the proximal muscles. Neck flexors and shoulder and ity in addition to onset. Associations with infections, medica- hip girdle muscles are commonly involved. Patients may expe- tions, occupational exposures, ultraviolet light, and other rience difficulty rising from a chair or climbing stairs. factors have been reported. The clearest associations have been Symptoms usually progress over months, except in inclusion with medications, including statins, cytokine-targeted thera body myositis, which progresses over years. Respiratory mus- pies (interferons and tumor necrosis factor inhibitors), and cles can be affected, and some patients experience difficulty checkpoint inhibitors. swallowing (dysphagia or dysmotility) related to involvement Immune mechanisms that contribute to IIM vary of the upper gastrointestinal tract. Cardiac muscle can be between subtypes and include the presence of T- and involved in some subsets of IIM. B-lymphocytic infiltrates, as well as increased cytokine and chemokine levels in muscle tissue. Autoantibodies are Pulmonary Disease expressed in many but not all patients; specific autoantibod Interstitial lung disease, most commonly nonspecific intersti ies and differing histologic patterns are associated with dis tial pneumonitis, occurs in both polymyositis and dermato- tinct sets ofclinical characteristics, suggesting that pathogenic myositis and is an important cause of morbidity and mortaliry mechanisms vary across subsets. Non-immune-mediated particularly in patients the antisynthetase syndrome (see mechanisms are also important, especially for the progres below). Muscle weakness of the chest wall can also cause sion to atrophy, fibrosis, and structural damage to muscle breathing difficulties. Pulmonary involvement is not typically tissue. seen in inclusion body myositis. 54 i

ldiopathic lnflammatory Myopathies Skin lnvolvement body myositis. Although clinically useful, these categories do Pathognomonic skin findings are associated with dermatomy- not fully account for the varying features within each group, ositis but not polymyositis. Mechanic's hands can occur in and alternative ways of subcategorizing patients are under patients with the antisynthetase syndrome associated with development. Some patients with dermatomyositis or polymy either polymyositis or dermatomyositis. ositis may further demonstrate the antisynthetase syndrome.

Skin lnvolvement body myositis. Although clinically useful, these categories do Pathognomonic skin findings are associated with dermatomy- not fully account for the varying features within each group, ositis but not polymyositis. Mechanic's hands can occur in and alternative ways of subcategorizing patients are under patients with the antisynthetase syndrome associated with development. Some patients with dermatomyositis or polymy either polymyositis or dermatomyositis. ositis may further demonstrate the antisynthetase syndrome. Cardiac Disease Dermatomyositis In addition to cardiac muscle involvement, arrhythmias, atrio In addition to muscle involvement, patients with dermatomy- ventricular block, and pericarditis have been reported. Patients ositis usually have characteristic skin findings (Table 27), includ- with myositis are at higher risk for heart failure and myocar ing heliotrope rash (Figure 34), Gottron papules (Figure 35), and dial infarction. Gottron sign. Other skin findings include periungual erythema, mechanic's hands (a dermatologic manifestation characterized Malignancy by rough, cracked, scaly skin along the lateral aspects of the There is a clear association between malignancy and IIM; digits and palms with horizontal lines resembling the weath patients with dermatomyositis have a 3 to l2-fold higher risk ered hands of a laborer; Figure 36), facial erythema or photo for malignancy than age matched populations. The associa- sensitive poikiloderma (shawl and V signs) (Figure 37), and tion between malignancy and polymyositis is smaller. The risk calcinosis cutis. Although both skin and muscle biopsies can be for malignancy peaks in the 3 years after the diagnosis of der- helpful for diagnosis and prognosis, some cases of dermatomy matomyositis or polymyositis. Commonly associated cancers ositis can be diagnosed on the basis of characteristic skin find- include ovarian, lung, pancreas, stomach, and colon cancers ings without a muscle biopsy. and lymphoma. Malignancy risk varies by antibody associa- A small subset of patients with dermatomyositis never tion (Table 26). Age and sex-appropriate cancer screening is develop muscle involvement (amyopathic dermatomyositis) ; indicated at the time of diagnosis of dermatomyositis or poly- these patients can be diagnosed with skin biopsy in the setting myositis and regularly for several years thereafter. Many of at least 6 months without muscle involvement. experts advocate CT of the chest, abdomen, and pelvis, par- ticularly in patients with dermatomyositis. Polymyositis Patients with polymyositis have proximal muscle weakness without the skin involvement of dermatomyositis. Because Types of ldiopathic patients with polymyositis lack pathognomonic clinical fea- lnflammatory Myositis tures, a muscle biopsy is recommended to confirm the diagno IIMs can be subcategorized into dermatomyositis, polymyosi- sis and differentiate this subgroup from other forms of myosi tis, immune-mediated necrotizing myopathy, and inclusion tis. In general, patients with polymyositis have a lower risk for

Cardiac Disease Dermatomyositis In addition to cardiac muscle involvement, arrhythmias, atrio In addition to muscle involvement, patients with dermatomy- ventricular block, and pericarditis have been reported. Patients ositis usually have characteristic skin findings (Table 27), includ- with myositis are at higher risk for heart failure and myocar ing heliotrope rash (Figure 34), Gottron papules (Figure 35), and dial infarction. Gottron sign. Other skin findings include periungual erythema, mechanic's hands (a dermatologic manifestation characterized Malignancy by rough, cracked, scaly skin along the lateral aspects of the There is a clear association between malignancy and IIM; digits and palms with horizontal lines resembling the weath patients with dermatomyositis have a 3 to l2-fold higher risk ered hands of a laborer; Figure 36), facial erythema or photo for malignancy than age matched populations. The associa- sensitive poikiloderma (shawl and V signs) (Figure 37), and tion between malignancy and polymyositis is smaller. The risk calcinosis cutis. Although both skin and muscle biopsies can be for malignancy peaks in the 3 years after the diagnosis of der- helpful for diagnosis and prognosis, some cases of dermatomy matomyositis or polymyositis. Commonly associated cancers ositis can be diagnosed on the basis of characteristic skin find- include ovarian, lung, pancreas, stomach, and colon cancers ings without a muscle biopsy. and lymphoma. Malignancy risk varies by antibody associa- A small subset of patients with dermatomyositis never tion (Table 26). Age and sex-appropriate cancer screening is develop muscle involvement (amyopathic dermatomyositis) ; indicated at the time of diagnosis of dermatomyositis or poly- these patients can be diagnosed with skin biopsy in the setting myositis and regularly for several years thereafter. Many of at least 6 months without muscle involvement. experts advocate CT of the chest, abdomen, and pelvis, par- ticularly in patients with dermatomyositis. Polymyositis Patients with polymyositis have proximal muscle weakness without the skin involvement of dermatomyositis. Because Types of ldiopathic patients with polymyositis lack pathognomonic clinical fea- lnflammatory Myositis tures, a muscle biopsy is recommended to confirm the diagno IIMs can be subcategorized into dermatomyositis, polymyosi- sis and differentiate this subgroup from other forms of myosi tis, immune-mediated necrotizing myopathy, and inclusion tis. In general, patients with polymyositis have a lower risk for TABLE 26. ldiopathic lnflammatory Myopathy-SpecificAntibodies AntibodyTarget Type of llM Skin Features Muscle Features Other Clinical Features TIF-1-1(formerly DM Classic skin rashes Typical lncreased cancer risk p1 55/1 40)

TABLE 26. ldiopathic lnflammatory Myopathy-SpecificAntibodies AntibodyTarget Type of llM Skin Features Muscle Features Other Clinical Features TIF-1-1(formerly DM Classic skin rashes Typical lncreased cancer risk p1 55/1 40) Mi-2 DM Classic skin rashes Typical Low risk for cancer and ILD NXP-2 DM Severe, ulcerative; high lncreased Low risk for ILD and high risk for calcinosis risk for cancer SAE DM, amyopathic DM Classic skin rashes Mild or none MDA5 DM, amyopathic DM Mechanic's hands Mild High risk for ILD Jo- 1 , EJ, OJ, PL-7 , Antisynthetase Mechanic's hands Typical Very high risk for ILD; often PL-12,KS,Ha,Zo syndrome includes arthritis and Raynaud phenomenon

SAE DM, amyopathic DM Classic skin rashes Mild or none MDA5 DM, amyopathic DM Mechanic's hands Mild High risk for ILD Jo- 1 , EJ, OJ, PL-7 , Antisynthetase Mechanic's hands Typical Very high risk for ILD; often PL-12,KS,Ha,Zo syndrome includes arthritis and Raynaud phenomenon SRP IMNM None Severe/necrotizing HMG-CoA IMNM None Severe/necrotizi ng May be associated with statin use NT5c1A IBM (poor sensitivity) None May include hand/ forearm weakness, may be asymmetric DM=dermatomyositis;HMG-CoA=hydroxy-methylglutarylcoenzymeA;lBM=inclusionbodymyositis;lM=idiopathicinflammatorymyopathy;lLD=ioterstitiallungdisease; IMNM = immune-mediated necrotizing myopathy; MDA5 = melanoma differentiation-associated gene 5; NXP 2 = nuclear matrix protein 2; SAE = small ubiquitin like modifier activating enzyme; SRP = signal recognition particle; TIF- 1 -1= transcription intermediary factor 1 1. 55