Mkgrady8 Gpmdc 3 Systemic Sclerosis (Scleroderma) And Inflammatory Myopathies

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systemic sclerosis is characterized by:

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acquired rheumatic disease of unknown cause; considerable morbidity and mortality and often progressive course; hallmark is thickening and hardening of the skin (scleroderma) (most pts also manifest characteristic abnormalities in the lungs, GI tract, kidneys, and heart); vascular dysfunction (Raynaud's phenomenon); over time structural alterations in small blood vessel and progressive fibrosis in multiple organs ensue and cause organ failure; no cure for systemic sclerosis

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systemic sclerosis: describe the scleroderma

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thick skin, widespread, disabling

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systemic sclerosis: descibe the visceral fibrosis

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inflammatory interstitial lung disease (fibrosis); myocardial fibrosis and conduction disorders; pulmonary hypertension; renovascular disease

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systemic sclerosis: describe the visceral organ involvement

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intestinal hypomotility= bacterial overgrowth, diarrhea/malabsorption, constipation/bloating; esophageal hypomotility= dysphagia; severe GI reflux= from decreased LES pressure, heartburn, esophageal ulcers/strictures

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systemic sclerosis: epidemiology

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annual incidence of 20 cases per million; onset usually between 4th and 7th decades; 3 to 1 women to men; AAs>whites

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systemic sclerosis: pathogenesis

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autoimmunity and inflammation, vascular injury and obliteration, fibrosis and matrix deposition in multiple organs; important to remember that this is not a vasculitis (inflammation in the vessels) but a vasculopathy (injury/damage)

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systemic sclerosis: the 2 distinct subsets of SSc

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diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc); at presentation the distinction is not always obvious

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systemic sclerosis: diffuse cutaneous (dcSSc)

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rapid and progressive involvement of the skin proximal to the elbows and knees, including the trunk, face, as well as distal extremities; visceral organ involvement common with pulmonary fibrosis and acute renal failure

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systemic sclerosis: limited cutaneous (lcSSc)

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skin thickening limited to the distal extremities, fingers, toes, and face, trunk is spared; pts with lcSSc develop Raynaud's phenomenon long before other manifestations appear; subset of pts with lcSSc have CREST syndrome= calcinosis cutis (calcifications under the skin)(use C to also remember that this has an autoantibody against centromeres), Raynaud's phenomenon, esophageal dysmotility, sclerodactyly (scleroderma of the fingers), telangiectasia; pts with the CREST syndrome generally have an indolent course and a good prognosis

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systemic sclerosis: diagnosis

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SSc is a clinical diagnosis; suggested by= skin induration, Raynaud's phenomenon, typical visceral and organ manifestations (esophageal reflux aka heartburn, telangiectasias, sclerodactylyl; antinuclear antibodies; occasionally full thickness skin biopsy may be requried

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systemic sclerosis: antibuclear antibodies

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present in virtually all pts with SSc at disease onset; topoisomerase-I (Scl-70)= dcDDc (30-40%)>lcSSc (10-15%), topoisomerase-I antibody positive pts have reduced survival compared with those without this antibody; anticentromere antibodies= lcSSc (40-50%)>>dcSSc(3%), strong association with pulmonary arterial hypertension (PAH), rarely seen with cardiac involvement, significant pulmonary fibrosis, or scleroderma renal crisis; anticentromere antibody positive pts have improved survival compared with those without this antibody; ANTIBODIES TO RNA POL III ASSOCIATED WITH INCREASED RISK FOR SCLERODERMA RENAL CRISIS (ON TEST)

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systemic sclerosis: treatment

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no treatment has altered the course of SSc except ACE-I in scleroderma renal crisis; therapy directly at specific organ involvement is often effective though

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systemic sclerosis: disease modifying therapy

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immunosuppressive agents have generally shown modest or no benefit; corticosteroids= may alleviate stiffness and aching in early stage dcSSc, associated with an increased risk for scleroderma renal crisis, should be avoided if possible, when absolutely necessary they should be given at the lowest dose possible and for brief periods only; cyclophosphamide= shown to reduce the progression of symptomatic interstitial lung disease in early SSc in retrospective and controlled clinical trials, beneficial effect was short lived, lots of potential side effects and complications; methotrexate and mycophenolate mofetil treatment were associated with a modest improvement in skin involvement in small clinical trials (generally well tolerated but need monitoring for toxicity)

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systemic sclerosis: treatment of organ specific complications: GI complications and vascular therapy and the treatment of Raynaud's phenomenon

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GI complications= significant GERD may occur in the absence of symptoms, treat all pts with proton pump inhibitors, bacterial overgrowth can be treated with short courses of rotating broad spectrum antibiotics such as metronidazole, erythromycin, and tetracycline; vascular therapy and the treatment of Raynaud's phenomenon= dress warmly to minimize cold exposure, calcium channel blockers nifedipine and diltiazem, might require alpha-1-adrenergic receptor blockers, 5-phosphodiesterase inhibitors, topical nitroglycerine, or IV prostaglandins

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systemic sclerosis: treatment of organ specific complications: renal crisis

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abrupt onset of accelerated hypertension; accompanied by a rise in serum creatinine; microscopic hematuria and proteinuria on urinalysis; TREAT WITH ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITOR (REGARDLESS OF SERUM CREATININE LEVEL), titrate to maintain a normal blood pressure preferably <125/75, responsible for a high level of mortality

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systemic sclerosis: treatment of organ specific complications: pulmonary arterial hypertension

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treatment should be started with an endothelin-1 receptor antagonist or a 5-phosphodiesterase inhibitor; oxygen for documented hypoxemia; lung transplantation remains an option for selected SSc pts with PAH who fail medical therapy

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systemic sclerosis: prognosis

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dcSSc= 10 yr survival rate is 20-55% and pulmonary complications are the leading cause of death; lcSSc= 10 yr survival rate is 70-75%

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name the idiopathic inflammatory myopathies (IIMs)

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polymyositis, dermatomyositis, connective tissue myositis, cancer associated myositis, inclusion body myositis

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the idiopathic inflammatory myopathies (IIMs): characterized by

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the clinical and pathologic effects of chronic muscle inflammation; unknown cause of any of them (idiopathic)

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IIMs: epidemiology

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incidence is 2-10 cases per million; 2 to 1 male to female; inclusion body myositis 3 to 1 male to female; bi modal distribution (7-15 and 30-50) cancer associated and inclusion body myositis usually present after age 50

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IIMs: an immune mediated component suggested by what

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inflammatory process; frequent finding of autoantibodies and other immune abnormalities; overlap with autoimmune diseases such as SLE; immunogenetic risk factors; clinical response to anti inflammatory agents; really remains unknown what causes it

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IIMs: what is found

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pathologic change in the muscle, skin, and other affected tissues characterized by focal collections of mononuclear cells; lymphocytes are the most commonly found in the infiltrates; myocytes show evidence of necrosis with degeneration and regeneration; often increased connective tissue or fibrosis in the interstitial areas around the myocytes

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IIMs: pathogensis

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polymyositis= CD8+ T cells surrounding and invading endomysial areas; dermatomyositis= B lymphocytes, dendritic cells, and CD4+ helper T cells in perimysial areas around the fascicles and small blood vessels

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IIMs: clinical presentation

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symmetrical, proximal muscle weakness is present in most cases; difficulty arising from chairs, getting out of cars, reaching overhead, or combing hair; generalized fatigue or muscle pain; if there are cutaneous findings think dermatomyositis

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IIMs: dermatomyositis cutaneous findings

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GOTTRON LESIONS= raised, often scaly, palpable, on the extensor surfaces of MCPs, PIPs, and DIPs, sometimes on elbows and knees (VIRTUALLY PATHOGNOMONIC FOR DERMATOMYOSITIS); periungual capillary changes; heliotrope rash= macules around the eyelids; V shaped rash on anterior chest; shawl sign (rash on back or neck, upper torso, and shoulders); mechanics hands= roughening, scaling, and erythematous fissuring of the palmar and lateral aspects of the fingers (can be seen in DM, PM)

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extramuscular manifestations of polymyositis an ddermatomyositis

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pulmonary= respiratory muscle weakness, aspiration, interstitial lung disease, pulmonary vasculitis; cardiac= heart block, arrhythmias, cardiomyopathy; GI= esophageal dysmotility, stomach, small or large intestine dysmotility; arthritis= nonerosive, symmetrical, small joint

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IIMs: diagnosis

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a careful medial and family history; exposure history; complete PE; direct lab testing (CPK and aldolase will be high (muscle enzymes that are leaking out)); electromyography may be helpful to rule out neurogenic causes; muscle biopsy should reveal the cause of muscle weakness in most cases; MRI may be useful to ID where inflammation is present and to increase the yield of muscle biopsy

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IIMs: what about autoantibodies as part of the diagnosis?

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autoantibodies are found in more than 90% of pts with polymyositis and dermatomyositis; none are diagnostic only supportive

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IIMs: more than 1/3 of pts have what

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autoantibodis known as myositis specific autoantibodies; most common autoantibodies= anti-Jo (a histidine transfer RNA (tRNA) synthase), anti-SRP (signal recognition particle), anti-Mi2 (a nuclear helicase); each of these autoantibodies is strongly associated with a distinct clinical presentation, response to therapy, and prognosis, suggesting that each autoantibody may be representative of a truly different myositis syndrome

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anti-Jo 1: associated with which condition, clinical features, treatment response

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both polymyositis and dermatomyositis; acute interstitial lung disease, fever, arthritis, Raynaud's phenomenon, mechanics hands; treatment response= moderate with persistent disease

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anti-SRP: associated with which condition, clinical features, treatment response

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polymyositis; abrupt onset, severe weakness, palpitations; treatment response= poor

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anti-Mi2: associated with which condition, clinical features, treatment response

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dermatomyositis; V sign and shawl sign; cuticular overgrowth; treatment response= good

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IIMs: association with cancer

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2-3x increase in risk of a variety of cancers within 2 yrs of the development of dermatomyositis (to a lesser extent with polymyositis); pts should be carefully assessed for malignant neoplasms (breast, prostate, ovaries, lungs, colon, etc)

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IIMs: therapy

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steroids (mainstay of therapy); frequently used glucocorticoid sparing agents (azathiopine, methotrexate, hydroxychloroquine); other agents sometimes used= cyclosporine, cyclophosphamide, mycophenolate, IVIG for dermatomyositis

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the big clinical differences between lcSSc and dcSSc

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dcSSc= widespread skin issues and renal crisis and vasculopathy common; lcSSc= skin issues are distal to the elbow or knee and no renal issues