Browse the corpus

Idiopathic lnflammatory Myopathies TABLE ??. Cutaneous Manifestations of Dermatomyositis Cutaneous Manifestation Location Clinical Appearance Gottron rash (Gottron Metacarpophalangeal and proximal Erythematous to violaceous papules; occasional scale; can papules and Gottron sign) interphalangeal joints (Gottron papules); ulcerate; atrophic scars may occur occasionally on distal interphalangeal joints, elbows, knees (Gottron sign) Heliotrope rash Eyelids Subtle pink to deep purple or brown discoloration; may be associated with edema of eyelids or periorbital edema V sign V of neck Erythematous to violaceous papules to patches Shawl sign Base of posterior neck to upper back Erythematous to violaceous papules to patches Fixed erythema Malar area (may cross nasolabial folds); Erythematous to violaceous papules to patches flanks of trunk Nail area changes Periungual area; cuticles Periungual erythema; capillary dilatation and dropout; cuticular hypertrophy; cuticular infarcts Mechanic's hands Lateral aspects of digits and palms Hyperkeratotic fissuring of the palmar and lateral surfaces of the fingers resembling the hands of a laborer

TABLE ??. Cutaneous Manifestations of Dermatomyositis Cutaneous Manifestation Location Clinical Appearance Gottron rash (Gottron Metacarpophalangeal and proximal Erythematous to violaceous papules; occasional scale; can papules and Gottron sign) interphalangeal joints (Gottron papules); ulcerate; atrophic scars may occur occasionally on distal interphalangeal joints, elbows, knees (Gottron sign) Heliotrope rash Eyelids Subtle pink to deep purple or brown discoloration; may be associated with edema of eyelids or periorbital edema V sign V of neck Erythematous to violaceous papules to patches Shawl sign Base of posterior neck to upper back Erythematous to violaceous papules to patches Fixed erythema Malar area (may cross nasolabial folds); Erythematous to violaceous papules to patches flanks of trunk Nail area changes Periungual area; cuticles Periungual erythema; capillary dilatation and dropout; cuticular hypertrophy; cuticular infarcts Mechanic's hands Lateral aspects of digits and palms Hyperkeratotic fissuring of the palmar and lateral surfaces of the fingers resembling the hands of a laborer F IG U R E 3 4. The heliotrope rash of dermatomyositis is a distinctive purple or FtG U RE 36. MechaniCs hands with hyperkeratotic, fissured skin on the palmar lilac, symmetric erythema of the eyelids that may be accompanied by slight edema, and lateral aspects of fingers seen in a patient with antisynthetase syndrome. generally focused around the orbits.

F IG U R E 3 4. The heliotrope rash of dermatomyositis is a distinctive purple or FtG U RE 36. MechaniCs hands with hyperkeratotic, fissured skin on the palmar lilac, symmetric erythema of the eyelids that may be accompanied by slight edema, and lateral aspects of fingers seen in a patient with antisynthetase syndrome. generally focused around the orbits. f I G U R E 3 5 . Gottron papules are violaceous, slightly scaly plaques over the bony FIGURE 37. The shawl sign demonstrating a photodistributed erythematous prominences on the hands. Ihe Gottron sign consists of similar findings over the patchy rash on the upper back in a patient with dermatomyositis. extensor surfaces of joints other than the hands, usually the elbows, knees, and ankles. 56

I i i ldiopathic lnflammatory Myopathies l pulmonary or other extramuscular disease features than those clinical features and different antibody associations. See Mixed t with dermatomyositis. Connective Tissue Disease and Undifferentiated Connective i Tissue Disease for further discussion. I Antisynthetase Syndrome .xIY P:01ilT5 '. t The antiqmthetase syndrome occurs in approximately 30% of I patients with dermatomyositis or polymyositis. The syndrome is . Pulmonary and cardiac involvement are important sources of morbidity and mortality in idiopathic associated with antibodies to aminoaryl-transfer RNA (IRNA) qmthetases (most commonly anti-Jo 1, directed at histidyl- infl ammatory myopathies. IRNA rynthetase) and is characterized by a high risk for and o Age- and sex-appropriate cancer screening is indicated i greater severity ofinterstitial lung disease. Other features include in dermatomyositis and polymyositis because of an arthritis, Raynaud phenomenon, and mechanic's hands. increased risk for malignancy.

patients with dermatomyositis or polymyositis. The syndrome is . Pulmonary and cardiac involvement are important sources of morbidity and mortality in idiopathic associated with antibodies to aminoaryl-transfer RNA (IRNA) qmthetases (most commonly anti-Jo 1, directed at histidyl- infl ammatory myopathies. IRNA rynthetase) and is characterized by a high risk for and o Age- and sex-appropriate cancer screening is indicated i greater severity ofinterstitial lung disease. Other features include in dermatomyositis and polymyositis because of an arthritis, Raynaud phenomenon, and mechanic's hands. increased risk for malignancy. i r Gottron rashes and heliotrope rashes are characteristic lmmune-Mediated Necrotizing Myopathy of dermatomyositis. Some patients previously included in the poll,rnyositis group o Immune-mediated necrotizing myopathy is character- are now recognized as belonging to a distinct subset known as ized by severe, rapidly progressive proximal muscle immune mediated necrotizing myopathy. This condition is weakness; high serum creatine kinase levels; and few characterized by rapidly progressive, severe muscle weakness; extramuscular manifestations. increased likelihood of muscle pain; high serum creatine o Inclusion body myositis is an insidious condition in kinase levels; and muscle biopsy specimens demonstrating older adults that affects both the proximal and distal prominent myonecrosis with only limited inflammation. These flexor muscles. patients tlpically lack extramuscular features. An immune- mediated mechanism is suggested by the presence of antibod ies to signal recognition particle or 3-hydroxy 3 methylglutaryt Diagnosis coenzyme A (HMG-CoA) reductase in about two thirds of IIM should be considered in any patient who has progressive patients (see Table 26). HMG CoA is the clinical target of action proximal muscle weakness without another explanation. of statins in lipid lowering, and statin exposure may result in antibodies to HMG-CoA reductase, which can sometimes lead Classification Criteria to immune-mediated necrotizing myopathy. However, statins Classification criteria are desigrred to allow researchers and cli- more commonly induce muscle disease through direct rather nicians to better distinguish IIM from other conditions affecting than autoimmune myotoxicity. In addition, many patients with muscles and to better differentiate among IIM subgroups. anti HMG CoA reductase antibodies have never been exposed Although intended for research studies, classification criteria to a pharmacologic statin. In patients with statin-triggered can help support a clinical diagnosis. Current criteria may allow immune mediated necrotizing myopathy, weakness may per classification without a muscle biopsy. These criteria first deflne sist or progress even after statins are discontinued. the probability of presence or absence of IIM and then apply the classification tree for subgroups of IIMs (Figure 38). Limitations lnclusion Body Myositis include the fact that there are too few patients with immune- Inclusion body myositis is an insidious condition affecting mediated necrotizing myopathy or antisynthetase syndrome to older adults. It is distinguishable from other forms of myositis characterize these subsets, along with lack of inclusion of MRI by its slow progression and different pattern of muscle involve- fi ndings or most myositis-specific antibodies. ment. Patients report a history of weakness for an average of 5 years before seeking care. Both proximal and distal muscle Muscle-Related Enzymes involvement occur; finger and forearm flexor involvement is Elevated serum muscle en-4lrnes are useful in dffierentiating nearly pathognomonic. Muscle distribution is usually but not intrinsic muscle disease from neurologic causes of weakness. always symmetric. Up to half of patients with inclusion body Elerated serum creatine kinase levels are a sensitive indicator of myositis have cricopharyngeal muscle involvement, leading to muscle pathologz, and lwels uzually parallel the severity of involve- dysphagia and increased risk for aspiration. ment. Aldolase level may be ele'"ated when serum creatine kinase Serum creatine kinase levels are elevated to a lesser extent levels are normal. Serum aminotransferase and serum lactate than seen in other forms of IIM. Autoantibodies are less often dehydrogenase levels may also be elevated but are nonspeciflc. present, but the anti NT5c1A autoantibody is found in up to Troponins can be used to screen for cardiac muscle involvement. t i half of patients and rarely in controls (see Table 26). ! Autoantibodies Overlap Syndromes Only about half of patients with IIM have identifiable autoan- I Other autoimmune connective tissue diseases may include tibodies. Some autoantibodies, such as antinuclear antibodies, myositis as a clinical feature but typically have other prominent lack specificity. The myositis specific antibodies have more

i r Gottron rashes and heliotrope rashes are characteristic lmmune-Mediated Necrotizing Myopathy of dermatomyositis. Some patients previously included in the poll,rnyositis group o Immune-mediated necrotizing myopathy is character- are now recognized as belonging to a distinct subset known as ized by severe, rapidly progressive proximal muscle immune mediated necrotizing myopathy. This condition is weakness; high serum creatine kinase levels; and few characterized by rapidly progressive, severe muscle weakness; extramuscular manifestations. increased likelihood of muscle pain; high serum creatine o Inclusion body myositis is an insidious condition in kinase levels; and muscle biopsy specimens demonstrating older adults that affects both the proximal and distal prominent myonecrosis with only limited inflammation. These flexor muscles. patients tlpically lack extramuscular features. An immune- mediated mechanism is suggested by the presence of antibod ies to signal recognition particle or 3-hydroxy 3 methylglutaryt Diagnosis coenzyme A (HMG-CoA) reductase in about two thirds of IIM should be considered in any patient who has progressive patients (see Table 26). HMG CoA is the clinical target of action proximal muscle weakness without another explanation. of statins in lipid lowering, and statin exposure may result in antibodies to HMG-CoA reductase, which can sometimes lead Classification Criteria to immune-mediated necrotizing myopathy. However, statins Classification criteria are desigrred to allow researchers and cli- more commonly induce muscle disease through direct rather nicians to better distinguish IIM from other conditions affecting than autoimmune myotoxicity. In addition, many patients with muscles and to better differentiate among IIM subgroups. anti HMG CoA reductase antibodies have never been exposed Although intended for research studies, classification criteria to a pharmacologic statin. In patients with statin-triggered can help support a clinical diagnosis. Current criteria may allow immune mediated necrotizing myopathy, weakness may per classification without a muscle biopsy. These criteria first deflne sist or progress even after statins are discontinued. the probability of presence or absence of IIM and then apply the classification tree for subgroups of IIMs (Figure 38). Limitations lnclusion Body Myositis include the fact that there are too few patients with immune- Inclusion body myositis is an insidious condition affecting mediated necrotizing myopathy or antisynthetase syndrome to older adults. It is distinguishable from other forms of myositis characterize these subsets, along with lack of inclusion of MRI by its slow progression and different pattern of muscle involve- fi ndings or most myositis-specific antibodies. ment. Patients report a history of weakness for an average of 5 years before seeking care. Both proximal and distal muscle Muscle-Related Enzymes involvement occur; finger and forearm flexor involvement is Elevated serum muscle en-4lrnes are useful in dffierentiating nearly pathognomonic. Muscle distribution is usually but not intrinsic muscle disease from neurologic causes of weakness. always symmetric. Up to half of patients with inclusion body Elerated serum creatine kinase levels are a sensitive indicator of myositis have cricopharyngeal muscle involvement, leading to muscle pathologz, and lwels uzually parallel the severity of involve- dysphagia and increased risk for aspiration. ment. Aldolase level may be ele'"ated when serum creatine kinase Serum creatine kinase levels are elevated to a lesser extent levels are normal. Serum aminotransferase and serum lactate than seen in other forms of IIM. Autoantibodies are less often dehydrogenase levels may also be elevated but are nonspeciflc. present, but the anti NT5c1A autoantibody is found in up to Troponins can be used to screen for cardiac muscle involvement. t i half of patients and rarely in controls (see Table 26). ! Autoantibodies Overlap Syndromes Only about half of patients with IIM have identifiable autoan- I Other autoimmune connective tissue diseases may include tibodies. Some autoantibodies, such as antinuclear antibodies, myositis as a clinical feature but typically have other prominent lack specificity. The myositis specific antibodies have more I 57 I

tdiopathic lnf lammatory Myopathies Patient meets the EULAR/ACR classification criteria for llM Age at onset of first symptom <1 8 years No Yes Heliotrope rash or Heliotrope rash or Gottron papules or Gottron papules or Gottron sign Gottron sign No Yes Objective symmetric weakness, usually progressive, of the proximal upper extremities or Clinical features* Objective symmetric weakness, usually or progressive, of the proximal lower extremities or Muscle biopsy feature** Neck flexors are relatively weaker than neck extensors or in the legs, proximal muscles are relatively weaker than distal muscles No Yes No Yes PM Juvenile myositis (rMNM) other than JDM *** IBM ADM DM JDM

PM Juvenile myositis (rMNM) other than JDM *** IBM ADM DM JDM tIGURE 38.2017 classificationcriteriaforadultandjuvenileidiopathicinflammatorymyopathies(llM)andtheirmajorsubgroups,fromtheEuropeanLeague Against Rheumatism (EULAR)/American College of Rheumatology (ACR). ADM = amyopathic dermatomyositis; DM = dermatomyositis; IBM = inclusion body myositis; IMNM = immune-mediated necrotizing myopathy; Jltyl = juvenile dermatomyositis; pM = polymyositis. *Finger flexor weakness and response to treatment: not improved. **Muscle biopsy: rimmed vacuoles required for diagnosls. ***Juvenilemyositis0lherthanJDl\,4wasdeve0pedbasedonexpertopini0f l[./lN[,4andhyp0myopalhicD]\.,lwereloofewtoallowsubclassification. IPMID:290795901d0i:10.1136/annrheumdis 2017 211468. Reproduced with permissi0n 01 BMJ Publishing Gr0up Ltd.

tIGURE 38.2017 classificationcriteriaforadultandjuvenileidiopathicinflammatorymyopathies(llM)andtheirmajorsubgroups,fromtheEuropeanLeague Against Rheumatism (EULAR)/American College of Rheumatology (ACR). ADM = amyopathic dermatomyositis; DM = dermatomyositis; IBM = inclusion body myositis; IMNM = immune-mediated necrotizing myopathy; Jltyl = juvenile dermatomyositis; pM = polymyositis. *Finger flexor weakness and response to treatment: not improved. **Muscle biopsy: rimmed vacuoles required for diagnosls. ***Juvenilemyositis0lherthanJDl\,4wasdeve0pedbasedonexpertopini0f l[./lN[,4andhyp0myopalhicD]\.,lwereloofewtoallowsubclassification. IPMID:290795901d0i:10.1136/annrheumdis 2017 211468. Reproduced with permissi0n 01 BMJ Publishing Gr0up Ltd. diagnostic and prognostic value and can be useful for identify- muscle fiber necrosis, degeneration, and regeneration, but ing risk for specific features or subsets (see Table 26). differ in the types and locations of the cell infiltrates. Muscle biopsy findings in inclusion body myositis include mononu- lmaging clear cell infiltrates, "rimmed" vacuoles, and a lack of muscle Although not required to diagnose IIMs, MRI is useful in iden cell necrosis. Electron microscopy can show characteristic ti[zing regions of active muscle inflammation and in guiding inclusion bodies. muscle biopsy. MRI can also assess the extent and severity of Skin biopsy can be useful in the diagnosis of dermatomy- muscle involvement and therapeutic efficacy. ositis, with typical findings including a perivascular lympho High-resolution CT should be used to assess for intersti- cytic infiltrate, vacuolar changes at the dermal-epidermal tial lung disease in high risk patients. junction, and increased dermal mucin.

diagnostic and prognostic value and can be useful for identify- muscle fiber necrosis, degeneration, and regeneration, but ing risk for specific features or subsets (see Table 26). differ in the types and locations of the cell infiltrates. Muscle biopsy findings in inclusion body myositis include mononu- lmaging clear cell infiltrates, "rimmed" vacuoles, and a lack of muscle Although not required to diagnose IIMs, MRI is useful in iden cell necrosis. Electron microscopy can show characteristic ti[zing regions of active muscle inflammation and in guiding inclusion bodies. muscle biopsy. MRI can also assess the extent and severity of Skin biopsy can be useful in the diagnosis of dermatomy- muscle involvement and therapeutic efficacy. ositis, with typical findings including a perivascular lympho High-resolution CT should be used to assess for intersti- cytic infiltrate, vacuolar changes at the dermal-epidermal tial lung disease in high risk patients. junction, and increased dermal mucin. xtY P0tilTs Electromyography o Elevated semm creatine kinase levels are a sensitive Although no single linding is pathognomonic, electromyogra indicator of muscle pathologz, and levels usually parallel phy may reveal findings characteristic of active myositis. This the severity of involvement. test can be uncomfortable, and results may be falsely normal . Myositis specific autoantibodies can be used to diag- in the presence ofactive disease because ofpatchy distribution nose and subcategorize some idiopathic inflammatory of muscle inflammation (sampling error). myopathies but are not present in all patients. r In patients with idiopathic inflammatory myopathies, Histopathology MRI can help locate a site for muscle biopsy and assess Muscle biopsy is valuable for diagnosing and distinguishing therapeutic efficacy. IIMs and for excluding metabolic myopathies, mitochondrial o Muscle biopsy is valuable for diagnosing idiopathic disease, and infection. inflammatory myopathies and for excluding metabolic Polymyositis and dermatomyositis share common histo myopathies, mitochondrial disease, and infection. pathologic features, including inflammatory cell infiltrates,

xtY P0tilTs Electromyography o Elevated semm creatine kinase levels are a sensitive Although no single linding is pathognomonic, electromyogra indicator of muscle pathologz, and levels usually parallel phy may reveal findings characteristic of active myositis. This the severity of involvement. test can be uncomfortable, and results may be falsely normal . Myositis specific autoantibodies can be used to diag- in the presence ofactive disease because ofpatchy distribution nose and subcategorize some idiopathic inflammatory of muscle inflammation (sampling error). myopathies but are not present in all patients. r In patients with idiopathic inflammatory myopathies, Histopathology MRI can help locate a site for muscle biopsy and assess Muscle biopsy is valuable for diagnosing and distinguishing therapeutic efficacy. IIMs and for excluding metabolic myopathies, mitochondrial o Muscle biopsy is valuable for diagnosing idiopathic disease, and infection. inflammatory myopathies and for excluding metabolic Polymyositis and dermatomyositis share common histo myopathies, mitochondrial disease, and infection. pathologic features, including inflammatory cell infiltrates, 58

Systemic Sclerosis l Management XEY POITII Glucocorticoids are the cornerstone of therapy for most forms o Initial treatment of most idiopathic inflammatory myo of tlMs. Starting dose varies by severity and organ involvement pathies consists of glucocorticoids, with additional but is fypically high (up to 1 mg/kg of prednisone) and should immunomodulatory agents (most commonly metho be tapered within 6 months. Prr-rlonged exposure to high-dose trexate and azathioprine) often required to control glucocorticoids, particularly in older patients, can lead to inflammation or serve as glucocorticoid-sparing agents. glucocorticoid induced myopathy, resulting in proximal mus . Prolonged symptoms before treatment, greater weak- cle weakness and diagnostic conlusion in a patient who had ness at presentation, extensive multisystem disease, co- previously been improving. occurrence of malignancy, and some autoantibodies Immunomodulatory agents are used to better manage and histologic patterns confer a poorer prognosis in intlammation or as glucocorticoid sparing agents; methotrex patients with idiopathic infl ammatory myopathies. ate and azathioprine are the prefbrred initial agents. Intravenous r Inclusion body myositis usually does not respond to immune globulin (IVIG) can be used in addition to or as an immunosuppression and typically results in wheelchair alternative to traditional agents; evidence for IVIG is strongest dependence within 10 to 15 years. fbr dermatomyositis and immune mediated necrotizing myo pathy. Mycophenolate, tacrolimus, cyclosporine, rituximab, or cyclophosphamide can be considered in patients in whom initial treatment has failed or who could not tolerate initial Systemic Sclerosis treatment. Immune mediated necrotizing myopathy is often Epidemiology and acute and severe and should be treated aggressively with com- binations of glucocorticoids and immunosuppressive agents; it Pathophysiology may respond particularly well to IVIG and rituximab. Statins Systemic sclerosis (SSc) is a multiorgan disease characterized by

l Management XEY POITII Glucocorticoids are the cornerstone of therapy for most forms o Initial treatment of most idiopathic inflammatory myo of tlMs. Starting dose varies by severity and organ involvement pathies consists of glucocorticoids, with additional but is fypically high (up to 1 mg/kg of prednisone) and should immunomodulatory agents (most commonly metho be tapered within 6 months. Prr-rlonged exposure to high-dose trexate and azathioprine) often required to control glucocorticoids, particularly in older patients, can lead to inflammation or serve as glucocorticoid-sparing agents. glucocorticoid induced myopathy, resulting in proximal mus . Prolonged symptoms before treatment, greater weak- cle weakness and diagnostic conlusion in a patient who had ness at presentation, extensive multisystem disease, co- previously been improving. occurrence of malignancy, and some autoantibodies Immunomodulatory agents are used to better manage and histologic patterns confer a poorer prognosis in intlammation or as glucocorticoid sparing agents; methotrex patients with idiopathic infl ammatory myopathies. ate and azathioprine are the prefbrred initial agents. Intravenous r Inclusion body myositis usually does not respond to immune globulin (IVIG) can be used in addition to or as an immunosuppression and typically results in wheelchair alternative to traditional agents; evidence for IVIG is strongest dependence within 10 to 15 years. fbr dermatomyositis and immune mediated necrotizing myo pathy. Mycophenolate, tacrolimus, cyclosporine, rituximab, or cyclophosphamide can be considered in patients in whom initial treatment has failed or who could not tolerate initial Systemic Sclerosis treatment. Immune mediated necrotizing myopathy is often Epidemiology and acute and severe and should be treated aggressively with com- binations of glucocorticoids and immunosuppressive agents; it Pathophysiology may respond particularly well to IVIG and rituximab. Statins Systemic sclerosis (SSc) is a multiorgan disease characterized by should be strictly avoided. fibrosis and vasculopathy. The skin is the most apparent target, Inclusion body myositis usually does not respond to but intemal organs are also affected. SSc is relatively rare, with a prevalence of 275 cases per million and an annual incidence of immunosuppression, and any therapeutic trials should be 19 cases per million. The peak incidence occurs in patients age 20 to discontinued if benefit is not appreciated. An initial response 50 years. It is more common among women and Black persons. to empiric glucocorticoids should encourage the physician to consider an alternative diagnosis. Reports suggest that IVIG Vascular injury vascular and visceral fibrosis, and innate may occasionally be helpful in managing dysphagia. and adaptive immune activation with autoantibody production play interactive roles in SSc. Genome wide association studies Physical therapy can help maintain muscle lunction and have identified up to 28 risk loci for SSc and underlined the should be universally recommended. importance of natural killer cell activity in SSc. One of the earli est SSc manifestations is Raynaud phenomenon, suggesting that vascular injury precedes the fibrotic reaction. With vascular Prognosis damage, the endothelial cells release endothelin-l, a potent The prognosis in IIM varies fiom resolution to severe, vasoconstrictor that also induces vascular smooth muscle prolif- treatment-resistant disease with functional impairment and eration and fibroblast activation. Platelet activation occurs con early mortality. The degree of serum creatine kinase elevation currentlywith subsequent release of growth factors that promote at diagnosis does not predict outcome. Prolonged disease further vasoconstriction, fibroblast activation, and collagen pro activity before treatment, greater weakness at presentation, duction. B cells are also activated and produce interleukin 6, extensive multisystem disease, and the co occurrence of which further stimulates fibroblasts and leads to autoantibody malignancy confers a poorer prognosis, as do certain myositis production. These and other processes cause increased collagen specific autoantibodies or histologic features. production and deposition by activated scleroderma fibroblasts, Patients with anti Jo 1 antibodies have worse outcomes along with progressive obliterative vasculopathy (due to interstitial lung disease), whereas those with anti Mi 2 antibodies often respond completely, despite a rapidly progressive course of dermatomyositis. Patients with Classification immune-mediated necrotizing myopathy may respond well The 2013 American College of Rheumatology/European to statin discontinuation (if appropriate) and aggressive League Against Rheumatism classification criteria for SSc pro immunosuppression. vide a rigorous definition of SSc that is not formally intended Giren the lack of effective treatment, patients with inclu Ibr diagnosis and may be too restrictive in clinical practice. sion body myositis typically demonstrate a slow and gradual However, they can provide useful guidance when a patient loss of function, with progression to wheelchair dependence presents with features suggesting SSc (Table 28). within 10 to 15 years of symptom development. However, life SSc is divided into three subtypes based on the extent expectancy does not appear to be affected. of skin involvement: Iimited cutaneous systemic sclerosis

should be strictly avoided. fibrosis and vasculopathy. The skin is the most apparent target, Inclusion body myositis usually does not respond to but intemal organs are also affected. SSc is relatively rare, with a prevalence of 275 cases per million and an annual incidence of immunosuppression, and any therapeutic trials should be 19 cases per million. The peak incidence occurs in patients age 20 to discontinued if benefit is not appreciated. An initial response 50 years. It is more common among women and Black persons. to empiric glucocorticoids should encourage the physician to consider an alternative diagnosis. Reports suggest that IVIG Vascular injury vascular and visceral fibrosis, and innate may occasionally be helpful in managing dysphagia. and adaptive immune activation with autoantibody production play interactive roles in SSc. Genome wide association studies Physical therapy can help maintain muscle lunction and have identified up to 28 risk loci for SSc and underlined the should be universally recommended. importance of natural killer cell activity in SSc. One of the earli est SSc manifestations is Raynaud phenomenon, suggesting that vascular injury precedes the fibrotic reaction. With vascular Prognosis damage, the endothelial cells release endothelin-l, a potent The prognosis in IIM varies fiom resolution to severe, vasoconstrictor that also induces vascular smooth muscle prolif- treatment-resistant disease with functional impairment and eration and fibroblast activation. Platelet activation occurs con early mortality. The degree of serum creatine kinase elevation currentlywith subsequent release of growth factors that promote at diagnosis does not predict outcome. Prolonged disease further vasoconstriction, fibroblast activation, and collagen pro activity before treatment, greater weakness at presentation, duction. B cells are also activated and produce interleukin 6, extensive multisystem disease, and the co occurrence of which further stimulates fibroblasts and leads to autoantibody malignancy confers a poorer prognosis, as do certain myositis production. These and other processes cause increased collagen specific autoantibodies or histologic features. production and deposition by activated scleroderma fibroblasts, Patients with anti Jo 1 antibodies have worse outcomes along with progressive obliterative vasculopathy (due to interstitial lung disease), whereas those with anti Mi 2 antibodies often respond completely, despite a rapidly progressive course of dermatomyositis. Patients with Classification immune-mediated necrotizing myopathy may respond well The 2013 American College of Rheumatology/European to statin discontinuation (if appropriate) and aggressive League Against Rheumatism classification criteria for SSc pro immunosuppression. vide a rigorous definition of SSc that is not formally intended Giren the lack of effective treatment, patients with inclu Ibr diagnosis and may be too restrictive in clinical practice. sion body myositis typically demonstrate a slow and gradual However, they can provide useful guidance when a patient loss of function, with progression to wheelchair dependence presents with features suggesting SSc (Table 28). within 10 to 15 years of symptom development. However, life SSc is divided into three subtypes based on the extent expectancy does not appear to be affected. of skin involvement: Iimited cutaneous systemic sclerosis 59