Pathogenesis And Clinical Manifestations Of Juvenile Dermatomyositis And Polymyositis

1,883 views
1,783 views

Published on

Revision sobre patogenesis y clinica de la dermatomiosistis y polimiosistis juvenil 2009

Published in: Health & Medicine, Business
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,883
On SlideShare
0
From Embeds
0
Number of Embeds
11
Actions
Shares
0
Downloads
59
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Pathogenesis And Clinical Manifestations Of Juvenile Dermatomyositis And Polymyositis

  1. 1. Pathogenesis and clinical manifestations of juvenile dermatomyositis and polymyositis Authors Clare Hutchinson, MDCM, FRCPC Brian Feldman, MD Section Editors Thomas JA Lehman, MD Jeremy M Shefner, MD, PhD Deputy Editor Melanie S Kim, MD Last literature review version 17.1: January 2009 | This topic last updated: February 9, 2009 (More) INTRODUCTION — Juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) are rare autoimmune myopathies in childhood. JDM is primarily a capillary vasculopathy, whereas JPM involves direct T-cell invasion of muscle fibers similar to that seen in adult polymyositis [1,2] . (See "Clinical manifestations and diagnosis of adult dermatomyositis and polymyositis"). The epidemiology, pathogenesis, and clinical manifestations of JDM and JPM will be reviewed here. Diagnosis and treatment of these disorders are discussed elsewhere. (See "Diagnosis of juvenile dermatomyositis and polymyositis" and see "Treatment of juvenile dermatomyositis and polymyositis"). EPIDEMIOLOGY — JDM is the most common idiopathic inflammatory myopathy of childhood accounting for approximately 80 percent of cases [3,4] . In population-based studies, JDM has a reported annual incidence that ranges from two to four cases per one million children [5-9] . The peak incidence is from 5 to 10 years of age [8, 9]. Girls are affected more often than boys with a two- to five-fold greater rate [7,8,10] . JPM occurs less frequently and accounts for only 3 to 6 percent of childhood idiopathic inflammatory myopathies [3,7] . PATHOGENESIS — Although the etiology remains unclear, it has been proposed that JDM and JPM are caused by an autoimmune reaction within the muscle tissue of genetically susceptible individuals, possibly in response to environmental triggers.
  2. 2. Genetic susceptibility — The occurrence of JPM and JDM in monozygotic twins and first-degree relatives suggests a genetic predisposition to these disorders in some families [11,12] . Certain HLA alleles also have been reported to be more common in patients with JDM; these include HLA-B8, HLA-DQA1*0501 and HLA-DQA1*0301 [13-15] . However, investigation of HLA class II alleles in patients with JDM has not identified any disease-associated allele [16] . Non-HLA associated genes, including genetic polymorphisms in tumor necrosis factor-alpha and interleukin-1 receptor antagonist, are known risk factors for the development of JDM or for the severity of its presentation [17-19] . Immunologic mechanisms — The following findings support the role of the immune system in the pathogenesis of JDM and JPM: T cell invasion of muscle fibers in patients with JPM [1] . Antinuclear antibodies are present in about 70 percent of patients with JDM and JPM. The specific antigen(s) for these antibodies have not yet been identified [20] . Myositis-specific autoantibodies (MSAs) are found in a minority of adults with DM and PM and are associated with specific clinical subgroups. However, MSAs have been identified in only a small number of children with inflammatory myopathy [21,22] . In one study of 38 children with JDM and other connective tissue diseases, MSAs were identified in 12 of 77 serum samples [21] . In a second study, MSAs (specifically anti Mi-2 autoantibodies) were found in only 2 of 42 patients with JDM. (See "Clinical manifestations and diagnosis of adult dermatomyositis and polymyositis", section on Myositis-specific autoantibodies). Similarity of observed histologic changes between JDM and chronic graft-versus-host disease. The presence of persistent maternal cells (maternal microchimerism), which triggers an immunologic response, has been proposed as a common pathogenetic pathway for the two disorders. Two studies have reported evidence of maternal microchimerism in the peripheral blood and muscle biopsies of boys with juvenile inflammatory myopathy [23,24] . Experimental data demonstrating increased T cell reactivity of in vitro peripheral blood mononuclear cells to heat shock protein (HSP) 60 in patients compared to normal controls [25] . HSPs have been proposed to have a regulatory role in chronic inflammatory diseases and may be an autoantigen for these disorders. (See "Immunopathogenesis of juvenile rheumatoid arthritis", section on Gamma-delta-T-Cell). Infection — Several observations have suggested that JDM may develop as an unusual response to infection in a genetically susceptible host: There is an increased prevalence of Coxsackie B antibodies in children with JDM compared to matched controls [26] . Case reports of viral isolation from muscle specimens in adult myositis have been described [27] . There is an association between echovirus infection and chronic polymyositis in children with agammaglobulinemia [28] . A seasonal variation of onset in JDM exists, with clustering of cases in the spring and summer [29] . Epitopes that are common both to human skeletal muscle and the bacteria Streptococcus pyogenes have been shown to be targets for cytotoxic T cell responses in patients with early, active JDM, indicating a possible link between an immune response to bacteria and the development of myositis [30] . Respiratory and gastrointestinal complaints and/or antibiotic use are common in the three months before diagnosis of JDM [31,32] .
  3. 3. However, attempts at demonstrating a viral etiology of JDM have failed. As an example, a recent study of 79 patients with new onset JDM found normal antibody titers to Herpes simplex virus, Coxsackievirus B 1 through 6, and Toxoplasma gondii [33] . Another report using the polymerase chain reaction was unable to demonstrate evidence of viral genetic material in the muscle of 20 individuals with active, untreated recent onset JDM [34] . Malignancy — Unlike adults, children with JDM or JPM do not have an increased risk of malignancy. In one Scottish population-based study, for example, cancer was not observed among 35 and 9 children with JDM or JPM, respectively [35] . There are rare case reports of solid tumors or hematologic malignancies in children with JDM; however, nothing suggests that the incidence of these disorders is greater than in the general population. (See "Malignancy in dermatomyositis and polymyositis"). Based upon these data, unless the presenting features are quite unusual, a search for malignancy does not need to be made when children present with idiopathic inflammatory myopathy. CLINICAL MANIFESTATIONS — Muscle weakness is the hallmark of JDM and JPM. In addition, patients with JDM present with characteristic rashes (show picture 1). Children with JDM and JPM also may have constitutional symptoms (fever, weight loss, fatigue, and headache), which may be the initial finding prior to the onset of muscle weakness, and in patients with JDM, rash. Because JPM is a rare entity, there is little descriptive clinical information about this disorder. This discussion will mainly focus on the clinical manifestations of JDM. The clinical presentation of JDM is exemplified by the two following case series. In the first review from a single tertiary Canadian center of 105 patients with JDM (mean age at diagnosis 7.6 years), the most common symptoms/findings and their frequency were noted at disease onset [4] . Gottron's rash: 91 percent Heliotrope rash: 83 percent Malar/facial rash: 42 percent Nailfold capillary change: 80 percent Myalgia/arthralgia: 25 percent Dysphonia or dysphagia: 24 percent Anorexia: 18 percent Fever: 16 percent The second case series is from the JDM Research Registry and included 166 newly diagnosed children living in the continental United States from 1994 to 1999 [10] . The mean age of diagnosis was 7.5 ± 3.8 years, and the median duration of symptoms prior to diagnosis was four months. There was no difference in the age of diagnosis or duration of untreated disease based upon gender or ethnicity. The initial symptoms were rash in 65 percent, weakness alone in 29 percent, or both rash and weakness in 6 percent of patients. The severity of the weakness increased with the duration of symptoms prior to diagnosis. Both the height and weight were lower compared to normative data from the National Health and Nutrition Examination Study (NHANES) III survey. Other findings included capillary dilation, arthritis, difficulty swallowing, abdominal pain, and fever.
  4. 4. Cutaneous manifestations — Cutaneous manifestations are common in children with JDM and include a characteristic heliotropic rash, gottron's papules, nailfold capillary changes, calcinosis, and skin ulcerations (show picture 2). Rash — Several distinct rashes (ie, heliotrope rash and Gottron's papules) may occur simultaneously with muscle involvement but can also be prominent prior to obvious muscular weakness. Rash is an important distinguishing feature between JDM and JPM, as it is not present in the latter condition. Skin disease may be exacerbated by exposure to sunlight and, as such, sun protection should be part of routine care in JDM. Heliotrope dermatitis is a reddish-purple rash on the upper eyelids, often accompanied by swelling of the eyelid (show picture 1). Malar and facial erythema may also be present. Heliotrope rash is one of the most common finding in patients with JDM, with a reported rate of 83 percent in the previously mentioned Canadian study, and a 94 percent rate in 44 patients from Hungary [4,36] . Periorbital edema, upper lid edema, or telangiectasia of the eyelid capillaries can be seen in 50 to 90 percent of children [37,38] . Gottron's papules are an erythematous, papulosquamous eruption over the dorsal surfaces of the knuckles (show picture 1). The term "Gottron's sign" is often used if the lesions are not papular. Similar lesions can occur over the extensor aspects of the elbows, knees, and medial malleoli, at times mimicking psoriasis. Gottron's papules are a common feature in patients with JDM, with a reported rate of 91 percent of Canadian and 77 percent of Hungarian patients from the previously mentioned studies [4,36] . Nailfold capillary changes — Nailfold capillary changes may be observed at the bedside or in clinic. These include capillary dilatation, tortuosity and dropout. The measured density of capillaries/mm may be a useful tool for monitoring clinical activity in JDM [39] (show picture 2, panel C). Skin ulcerations — Ulcerative skin disease is a serious and potentially life-threatening manifestation of JDM (show picture 2, panel E). Ulcers presumably reflect significant vasculopathy in the skin (with tissue hypoxia and necrosis), and may signal vasculopathy in other organs (especially the lungs and gut). Patients with ulcerative lesions have more severe disease and a worse prognosis. This was illustrated by a retrospective case series that included 6 of 47 children with JDM with extensive ulcerative skin vasculitis present at diagnosis [40] . These six patients continued to have persistent muscle weakness, elevations of muscle enzyme activity, and severe generalized cutaneous vasculitis despite receiving corticosteroid therapy. In another study, 10 of 29 patients had a chronic disease course characterized by ulcerative cutaneous and gastrointestinal lesions [41] . Two of the 10 died due to complications including gastrointestinal perforation, five had severe musculoskeletal and cutaneous damage, and three had no residual disease [41] . Calcinosis — Dystrophic calcification or calcinosis (soft tissue calcification) generally develops within a few years of diagnosis (show picture 2, panel D) [3,42] . Reports of its prevalence vary from 30 to 50 percent [40,43] . In contrast, one study of 144 patients from the United Kingdom reported a much lower calcinosis rate of 6 percent [3] .
  5. 5. Five distinct patterns of calcinosis have been described [40,44] : Small, scattered, superficial plaques or nodules, usually on the extremities. These lesions often do not interfere with function, but may be painful and may develop spontaneous cellulitis-like inflammation (sometimes with drainage of toothpaste-like calcium soap). Inflamed superficial calcinosis must be differentiated from superinfected lesions. Superficial calcinosis often regresses spontaneously over a period of years. Deep tumoral muscle calcification often found in the proximal muscle groups that may interfere with joint motion. These deposits may ulcerate or extrude calcific material through the skin. These may require surgical debridement in order to maximize joint function. Diffuse deposits along myofascial planes that may limit joint motion and may be painful. Mixed forms of the above three types may be seen. Extensive exoskeleton-like calcium deposits that result in serious limitations in function. Patients with this form of calcinosis often have a history of severe, unremitting disease course associated with ulcerative cutaneous disease. Calcinosis has been associated with the following risk factors: Delay in diagnosis or treatment, or inadequate treatment [40,45] . Tissue necrosis factor (TNF) alpha-308A genotype (this allele is associated with increased levels of TNF alpha) [17] . Patients below five years of age have been reported to be more likely to develop calcinosis [46] . However, another study found no association between age of onset of JDM and calcinosis. Amyopathic dermatomyositis — The cutaneous manifestations of JDM may appear in the absence of clinically apparent muscle disease in a small number of children. Children with this presentation, termed amyopathic JDM, may never develop muscle weakness, but amyopathic JDM may reflect an early phase in the disease course before muscle weakness has yet developed. The skin findings may require therapy but may remit in some without systemic therapy [47-49] . However, all such children require evaluation by an experienced pediatric rheumatologist or neurologist to assure that they are not, in fact, weak. Muscle weakness — The inflammatory myopathies are characterized by symmetric, proximal muscle weakness. This may present with functional limitations, such as difficulty getting up from the floor, getting into and out of motor vehicles, or climbing stairs. Washing or grooming hair may pose a challenge, and severely affected children may not be able to feed themselves. In very young children, frequent falls may be an important symptom. A Gower's sign is frequently present. Weakness of the palate and cricopharyngeal muscle may result in problems swallowing, a nasal voice, tracheal aspiration, and reflux of food into the nasopharynx. Involvement of the upper esophagus can lead to dysphagia for solids and liquids. Arthritis — Non-erosive arthralgia and arthritis may be present at the time of diagnosis or during the disease course [3,4,50] . Contractures may be seen but are usually related to muscle weakness rather than arthritis.
  6. 6. Lipodystrophy — Acquired lipodystrophy (show picture 2, panel F) and associated metabolic abnormalities such as insulin resistance, acanthosis nigricans, and type 2 diabetes are being increasingly recognized in patients with JDM. In a study of 20 patients with JDM, 4 were found to have lipodystrophy accompanied by either insulin resistance or type 2 diabetes, while an additional 13 had glucose and lipid abnormalities without evidence of lipodystrophy [51] . In another study of 20 patients, 13 patients had lipoatrophy based upon subcutaneous fat quantification by skinfold caliper including 8 patients with physical findings of lipodystrophy [52] . Oral glucose tests were normal in all patients, but 12 of 18 patients tested were found to have hypertriglyceridemia. JDM appears to be a common cause of lipodystrophy children. In a retrospective review, JDM alone or in association with other autoimmune disease (eg, juvenile rheumatoid arthritis) was the underlying disease in 18 of 23 children with acquired lipodystrophy. Other findings included acanthosis nigricans (n = 5 patients), hyperpigmentation (n = 5), elevated liver enzymes (n = 5), and hypertension (n =3) [53] . Other findings — Other clinical manifestations of JDM include: Pulmonary involvement — Pulmonary manifestations are much less common in children than adults, but interstitial lung disease may occur [54] . Gastrointestinal vasculopathy — Gastrointestinal (GI) tract involvement is relatively rare, but can be life-threatening. Affected patients may present with abdominal pain, pneumatosis intestinalis, gastrointestinal bleeding, or perforation [2,55] . Acute GI vasculitis and chronic abdominal endarteropathy have been described in patients with JDM, indicating that the underlying pathology leading to ulceration and perforation of the intestines is complex [56] . Any patient with JDM experiencing abdominal pain that persists or progresses warrants careful investigation because GI vasculopathy may occur late in the disease course or in a patient with only mild myositis. Of note, abdominal radiographs and stool testing for occult blood may be normal in patients with GI involvement. The need for further investigation, such as abdominal ultrasonography or computed tomography (CT), must be guided by clinical suspicion for significant GI involvement. Anasarca — The presence of anasarca at presentation may be a poor prognostic sign indicating severe disease that may respond very slowly to treatment and may not respond to corticosteroids alone. The generalized edema may be the result of a diffuse capillary leak resulting from vascular endothelial damage [57] . SUMMARY — Juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) are rare autoimmune myopathies affecting children. JDM is the most common of these disorders accounting for 80 percent of cases with a reported incidence that range from two to four cases per million children. (See "Epidemiology" above). Although the etiology of JDM and JPM remains unclear, it has been proposed that these disorders are caused by an autoimmune reaction within the muscle tissue of genetically susceptible individuals, possibly in response to environmental triggers. (See "Pathogenesis" above). Symmetrical proximal muscle weakness is the hallmark clinical feature of these two disorders. In addition, heliotrope rash (reddish-purple rash on the upper eyelids, often accompanied by swelling of the eyelid, show picture 1) and Gottron's papules
  7. 7. (erythematous, papulosquamous eruption over the dorsal surfaces of the knuckles, show picture 1) are characteristic rashes of JDM. Children with JDM and JPM also may have constitutional symptoms (fever, weight loss, fatigue, and headache), which may be the initial finding prior to the onset of muscle weakness, and in patients with JDM, rash. Other clinical manifestations include nailfold capillary changes, skin ulcerations, calcinosis (soft tissue calcification), non-erosive arthalgia and arthritis, lipodystrophy, and insulin resistance (show picture 2). Gastrointestinal vasculopathy is a relative rare, but life-threatening manifestation that may present as abdominal pain, pneumatosis intestinalis, gastrointestinal bleeding, or perforation. (See "Clinical manifestations" above). REFERENCES Arahata, K, Engel, AG. Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 1984; 16:193. Banker, BQ, Victor, M. Dermatomyositis (systemic angiopathy) of childhood. Medicine (Baltimore) 1966; 45:261. McCann, LJ, Juggins, AD, Maillard, SM, et al. The Juvenile Dermatomyositis National Registry and Repository (UK and Ireland)--clinical characteristics of children recruited within the first 5 yr. Rheumatology (Oxford) 2006; 45:1255. Ramanan, AV, Feldman, BM. Clinical features and outcomes of juvenile dermatomyositis and other childhood onset myositis syndromes. Rheum Dis Clin North Am 2002; 28:833. Oddis, CV, Conte, CG, Steen, VD, Medsger, TA Jr. Incidence of polymyositis- dermatomyositis: a 20-year study of hospital diagnosed cases in Allegheny County, PA 1963-1982. J Rheumatol 1990; 17:1329. Pelkonen, PM, Jalanko, HJ, Lantto, RK, et al. Incidence of systemic connective tissue diseases in children: a nationwide prospective study in Finland. J Rheumatol 1994; 21:2143. Symmons, DP, Sills, JA, Davis, SM. The incidence of juvenile dermatomyositis: results from a nation-wide study. Br J Rheumatol 1995; 34:732. Mendez, EP, Lipton, R, Ramsey- Goldman, R, et al. US incidence of juvenile dermatomyositis, 1995-1998: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Registry. Arthritis Rheum 2003; 49:300. Gardner-Medwin, JM, Dolezalova, P, Cummins, C, Southwood, TR. Incidence of Henoch- Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 2002; 360:1197. Pachman, LM, Abbott, K, Sinacore, JM, et al. Duration of illness is an important variable for untreated children with juvenile dermatomyositis. J Pediatr 2006; 148:247. Harati, Y, Niakan, E, Bergman, EW. Childhood dermatomyositis in monozygotic twins. Neurology 1986; 36:721. Leonhardt, T. Familial occurrence of collagen diseases. II. Progressive systemic sclerosis and dermatomyositis. Acta Med Scand 1961; 169:735. Mamyrova, G, O'Hanlon, TP, Monroe, JB, et al. Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians. Arthritis Rheum 2006; 54:3979. Pachman, LM, Jonasson, O, Cannon, RA, Friedman, JM. Increased frequency of HLA-B8 in juvenile dermatomyositis. Lancet 1977; 2:1238. Reed, AM, Pachman, LM, Hayford, J, Ober, C. Immunogenetic studies in families of children with juvenile dermatomyositis. J Rheumatol 1998; 25:1000. Vavrincova, P, Havelka, S, Cerna, M, Stastny, P. HLA class II alleles in juvenile dermatomyositis. J Rheumatol Suppl 1993; 37:17. Pachman, LM, Liotta- Davis, MR, Hong, DK, et al. TNFalpha-308A allele in juvenile dermatomyositis: association with
  8. 8. increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications. Arthritis Rheum 2000; 43:2368. Rider, LG, Artlett, CM, Foster, CB, et al. Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies. Clin Exp Immunol 2000; 121:47. Mamyrova, G, O'Hanlon, TP, Sillers, L, et al. Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis. Arthritis Rheum 2008; 58:3941. Pachman, LM. Inflammatory myopathy in children. Rheum Dis Clin North Am 1994; 20:919. Rider, LG, Miller, FW, Targoff, IN, et al. A broadened spectrum of juvenile myositis. Myositis-specific autoantibodies in children. Arthritis Rheum 1994; 37:1534. Feldman, BM, Reichlin, M, Laxer, RM, et al. Clinical significance of specific autoantibodies in juvenile dermatomyositis. J Rheumatol 1996; 23:1794. Artlett, CM, Ramos, R, Jiminez, SA, et al. Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group. Lancet 2000; 356:2155. Reed, AM, Picornell, YJ, Harwood, A, Kredich, DW. Chimerism in children with juvenile dermatomyositis. Lancet 2000; 356:2156. Elst, EF, Klein, M, de Jager, W, et al. Hsp60 in inflamed muscle tissue is the target of regulatory autoreactive T cells in patients with juvenile dermatomyositis. Arthritis Rheum 2008; 58:547. Christensen, ML, Pachman, LM, Schneiderman, R, et al. Prevalence of Coxsackie B virus antibodies in patients with juvenile dermatomyositis. Arthritis Rheum 1986; 29:1365. Tang, TT, Sedmak, GV, Siegesmund, KA, McCreadie, SR. Chronic myopathy associated with coxsackievirus type A9. A combined electron microscopical and viral isolation study. N Engl J Med 1975; 292:608. Webster, AD, Tripp, JH, Hayward, AR, et al. Echovirus encephalitis and myositis in primary immunoglobulin deficiency. Arch Dis Child 1978; 53:33. Pachman, LM, Hayford, JR, Hochberg, MC. Seasonal onset in juvenile dermatomyositis (JDMS): an epidemiological study. Arthritis Rheum 1992; 35:S88. Massa, M, Costouros, N, Mazzoli, F, et al. Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis. Arthritis Rheum 2002; 46:3015. Pachman, LM, Lipton, R, Ramsey- Goldman, R, et al. History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry. Arthritis Rheum 2005; 53:166. Manlhiot, C, Liang, L, Tran, D, et al. Assessment of an infectious disease history preceding juvenile dermatomyositis symptom onset. Rheumatology (Oxford, England) 2008; 47:526. Pachman, LM, Hayford, JR, Hochberg, MC, et al. New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis. Arthritis Rheum 1997; 40:1526. Pachman, LM, Litt, DL, Rowley, AH, et al. Lack of detection of enteroviral RNA or bacterial DNA in magnetic resonance imaging-directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis. Arthritis Rheum 1995; 38:1513. Stockton, D, Doherty, VR, Brewster, DH. Risk of cancer in patients with dermatomyositis or polymyositis, and follow-up implications: a Scottish population-based cohort study. Br J Cancer 2001; 85:41. Constantin, T, Ponyi, A, Orban, I, et al. National registry of patients with juvenile idiopathic inflammatory myopathies in Hungary--clinical characteristics and disease course of 44 patients with juvenile dermatomyositis. Autoimmunity 2006; 39:223. Akikusa, JD, Tennankore, DK, Levin, AV, Feldman, BM. Eye findings in patients with juvenile dermatomyositis. J Rheumatol 2005; 32:1986. COOK, CD, ROSEN, FS, BANKER, BQ. DERMATOMYOSITIS AND FOCAL SCLERODERMA. Pediatr Clin North Am 1963; 10:979. Smith, RL, Sundberg, J, Shamiyah, E, et al.
  9. 9. Skin involvement in juvenile dermatomyositis is associated with loss of end row nailfold capillary loops. J Rheumatol 2004; 31:1644. Bowyer, SL, Blane, CE, Sullivan, DB, Cassidy, JT. Childhood dermatomyositis: factors predicting functional outcome and development of dystrophic calcification. J Pediatr 1983; 103:882. Crowe, WE, Bove, KE, Levinson, JE, Hilton, PK. Clinical and pathogenetic implications of histopathology in childhood polydermatomyositis. Arthritis Rheum 1982; 25:126. Huber, AM, Lang, B, LeBlanc, CM, et al. Medium- and long-term functional outcomes in a multicenter cohort of children with juvenile dermatomyositis. Arthritis Rheum 2000; 43:541. Sallum, AM, Pivato, FC, Doria-Filho, U, et al. Risk factors associated with calcinosis of juvenile dermatomyositis. J Pediatr (Rio J) 2008; 84:68. Blane, CE, White, SJ, Braunstein, EM, et al. Patterns of calcification in childhood dermatomyositis. AJR Am J Roentgenol 1984; 142:397. Pachman, LM, Hayford, JR, Chung, A, et al. Juvenile dermatomyositis at diagnosis: clinical characteristics of 79 children. J Rheumatol 1998; 25:1198. Marhaug, G, Shah, V, Shroff, R, et al. Age-dependent inhibition of ectopic calcification: a possible role for fetuin-A and osteopontin in patients with juvenile dermatomyositis with calcinosis. Rheumatology (Oxford) 2008; 47:1031. Euwer, RL, Sontheimer, RD. Amyopathic dermatomyositis: a review. J Invest Dermatol 1993; 100:124S. Plamondon, S, Dent, PB. Juvenile amyopathic dermatomyositis: results of a case finding descriptive survey. J Rheumatol 2000; 27:2031. Stonecipher, MR, Jorizzo, JL, White, WL, et al. Cutaneous changes of dermatomyositis in patients with normal muscle enzymes: dermatomyositis sine myositis?. J Am Acad Dermatol 1993; 28:951. Tse, S, Lubelsky, S, Gordon, M, et al. The arthritis of inflammatory childhood myositis syndromes. J Rheumatol 2001; 28:192. Huemer, C, Kitson, H, Malleson, PN, et al. Lipodystrophy in patients with juvenile dermatomyositis--evaluation of clinical and metabolic abnormalities. J Rheumatol 2001; 28:610. Verma, S, Singh, S, Bhalla, AK, Khullar, M. Study of subcutaneous fat in children with juvenile dermatomyositis. Arthritis Rheum 2006; 55:564. Pope, E, Janson, A, Khambalia, A, Feldman, B. Childhood acquired lipodystrophy: a retrospective study. J Am Acad Dermatol 2006; 55:947. Kobayashi, I, Yamada, M, Takahashi, Y, et al. Interstitial lung disease associated with juvenile dermatomyositis: clinical features and efficacy of cyclosporin A. Rheumatology (Oxford) 2003; 42:371. Downey, EC, Jr., Woolley, MM, Hanson, V. Required surgical therapy in the pediatric patient with dermatomyositis. Arch Surg 1988; 123:1117. Mamyrova, G, Kleiner, DE, James-Newton, L, et al. Late-onset gastrointestinal pain in juvenile dermatomyositis as a manifestation of ischemic ulceration from chronic endarteropathy. Arthritis Rheum 2007; 57:881. Mitchell, JP, Dennis, GJ, Rider, LG. Juvenile dermatomyositis presenting with anasarca: A possible indicator of severe disease activity. J Pediatr 2001; 138:942.

×