Dermatology Online Journal

Juvenile dermatomyositis in an 8-year-old boy
Astrid Schmieder¹, Gregor von Komorowski², Wiebke K Peitsch¹, Sergij Goerdt¹, Matthias Goebeler^1,3
Dermatology Online Journal 15 (6): 3

1. Department of Dermatology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
2. Department of Pediatrics, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
3. Department of Dermatology, University Hospital Giessen, Giessen, Germany. matthias.goebeler@derma.med.uni-giessen.de

---

Abstract

Juvenile dermatomyositis (JDM) is a rare autoimmune vasculopathy affecting children and adolescents under the age of 18. In this report we describe an 8-year-old boy who, besides myopathy, presented with an uncommonly broad spectrum of skin findings that had evolved after summer holidays at the Mediterranean Sea. Upon treatment with intravenous methylprednisolone the patient's condition considerably improved. Our case report illustrates that JDM requires comprehensive evaluation and multidisciplinary management.

---

Introduction

Juvenile dermatomyositis (JDM) is a rare autoimmune vasculopathy of childhood that preferentially affects dermal and muscular vessels. By definition, the onset of JDM is prior to the age of 18, whereas the average onset is in the 7th to 8th year of life, with a slight preference for the female gender [1]. As with many other autoimmune diseases, the etiology of JDM is not yet clear, but there is a disproportional association with certain HLA alleles, such as B8 [2], DRB1*0301 [3], DQA1*0501 [3] and DQA1*0301 [4] has been reported, suggesting genetic susceptibility. Polymorphisms of both the TNF-α promoter [5] and the interleukin-1 receptor antagonist [6] have been identified as additional risk factors. However, genetic susceptibility alone does not sufficiently explain disease onset. Environmental factors such as bacterial and viral infections (group A β-hemolytic streptococci [7], enterovirus [8], Coxsackie virus [9]) and, as presumably in the case presented here, exposure to UV light have to be considered as important trigger factors.

Case

Figure 1	Figure 2
Figure 1. Malar and periorbital heliotrope rash Figure 2. Hyperkeratotic nailfolds with erosions and Gottron papules over metacarpophalangeal and proximal interphalangeal joints

Figure 3
Figure 3. V sign presenting as poikilodermatous erythematous eruption at the upper thoracic aperture

An 8-year-old boy presented to our department with malar and periorbital heliotrope erythema (Fig. 1). His parents reported that the rash had started two months before, during summer holidays at the Mediterranean Sea. The boy complained of itching, but there was no history of muscle weakness, arthralgia or preceding infection. Physical examination revealed erythematous scaly plaques (Gottron papules) over metacarpophalangeal and proximal interphalangeal joints. Nailfolds were hyperkeratotic and showed erosions (Fig. 2). Poikilodermatous reticulate erythematous lesions were apparent at the upper thoracic, V-sign location (Fig. 3), the lateral sides of upper arms and thighs, and over the medial malleoli (Fig. 4).There was no lymphadenopathy.

Figure 4	Figure 5
Figure 4. Erythematous lesions over the malleoli Figure 5. Histopathology: A lesional skin biopsy obtained from the upper thigh showed a moderate perivascular lymphocytic infiltration in the upper and lower dermis compatible with dermatomyositis (H&E)

Laboratory examination revealed elevated levels of lactate dehydrogenase(LDH) (492 U/l), creatine kinase (1285 U/l), alanine transaminase (ALT) (118 U/l) and aspartate aminotransferase (AST) (72 U/L). Increased circulating von Willebrand factor antigen, a marker of vasculopathy, was also identified. Autoantibodies including ANA, anti-MI-2-, anti-Jo-1-, and anti-AMA-M2 were negative. All other laboratory data were within normal range. Chest X-ray, electrocardiogram and echocardiography showed no abnormalities, whereas abdominal ultrasound revealed moderate hepatomegaly. Because the muscle enzymes were considerably elevated, magnetic resonance imaging (MRI) was performed that showed edema of the upper arm and shoulder muscles; there were no signs of calcification or lipodystrophy. Based on clinical appearance, laboratory and imaging data, the diagnosis of juvenile dermatomyositis (JDM) was made. Pulse corticosteroid therapy with intravenous methylprednisolone (18.75 mg/kg body weight per day) was initiated and was administered on 4 consecutive days, every 4 weeks; in addition, omeprazole (40 mg per day) was given. The therapy was well tolerated without apparent side effects. The skin lesions almost completely resolved after the second pulse. Creatine kinase and lactate dehydrogenase gradually improved. The patient has now been followed-up for 6 months. At his last presentation, skin manifestations had disappeared and muscle enzymes were within normal range. After the fourth methylprednisolone treatment, intervals between the pulses were prolonged to 6 weeks and there were no signs of recurrence. Continuation of this treatment is planned for at least 18 months.

Discussion

Diagnostic criteria for JDM are currently still based on those established by Bohan and Peter in 1975 [10], which include a characteristic skin eruption, symmetrical proximal muscle weakness, elevated muscle enzymes, pathological muscle histology, and myopathic electromyographic changes. The presence of 3 of these criteria characterizes definite JDM, whereas the prevalence of 2 criteria makes the diagnosis probable.

However, early diagnosis is often hampered by the nonspecific nature of the initial signs of JDM, such as fatigue, fever, weight loss, irritability, myalgia, and arthralgia. Identification of characteristic skin lesions may help establish an early diagnosis. Typical cutaneous lesions include a characteristic periorbital heliotrope rash (present in more than two-thirds of patients), facial malar rash, Gottron papules (livid scaly plaques on the extensor surface of joints), and nailfold changes that may present as periungual infarcts. Nailfold capillaroscopy shows reduced capillary density, capillary dropout, branching, and dilatation [11]. In addition, nonspecific eruptions on the extremities and mouth, skin ulcers, lipodystrophy [12], psoriasiform scalp dermatitis [13], and limb edema have been described. Particular attention should be given to dystrophic calcification that occurs in up to 30 percent of cases [14] and may lead to long-term disabilities and ulceration.

Myopathy, mostly affecting the proximal muscles, is present in about 95 percent of dermatomyositis cases; the existence of amyopathic dermatomyositis is controversial. Myalgia may precede skin rashes, thereby posing a diagnostic challenge [14, 15]. With respect to the invasive nature of muscle biopsy and electromyography, MRI is frequently used as an alternative diagnostic procedure in pediatric patients. Even though our patient never complained of muscle weakness, MRI analysis showed edema of the shoulder and proximal arm musculature indicating muscular inflammation. Clearly, MRI cannot reveal the cause for muscular edema. However, in combination with elevated muscle enzymes and typical skin lesions, this finding is highly suggestive of dermatomyositis. In the international consensus survey of the diagnostic criteria for JDM, MRI was appreciated as one of the most important diagnostic methods to be added to the revised criteria [16]. Other organs that need thorough assessment are the gastrointestinal (GI) and respiratory tracts. Vasculopathy may rarely affect the vessels of the GI tract, potentially resulting in malabsorption, ulceration, acute hemorrhage, and infarction. Regarding the respiratory tract, muscle weakness may lead to aspiration. Moreover, an increased incidence of interstitial lung disease has been reported. Therefore, GI symptoms and dyspnea should always be taken seriously and assessed clinically and radiologically [17]. Notably, in contrast to adult dermatomyositis, JDM is not associated with malignancies and therefore does not require the corresponding assessments. Autoantibodies such as ANA, anti-Mi-2 or anti-Jo-1 can only be detected in a minority of JDM cases and were negative in our patient. Ribonucleoprotein (RNP) antibodies, which may be indicative of mixed connective tissues disease, were not assessed. Indeed, if a patient with clinical complaints resembling dermatomyositis suffers from persistent arthritis, mixed connective tissue disease is an important item in the differential diagnosis. However, our patient did not report any arthralgias, making this diagnosis less likely.

Histopathologic findings characteristic of dermatomyositis include a moderate perivascular lymphocytic infiltrate around the superficial and deep vascular plexus of the dermis with some lymphocytes scattered at the dermoepidermal junction. Moreover, moderate dermal mucin deposits and widely dilated venules, especially in the superficial dermis, can be observed. These features are not highly specific and sometimes hard to distinguish from findings in discoid lupus erythematosus (LE). In discoid LE, however, the lymphocytic infiltrate is typically more pronounced and concentrated in deep perivascular regions. Furthermore, lymphocytes are also seen around hair follicles, often with early signs of alopecia. A thickened epidermal basement membrane, vacuolar alteration, and necrotic keratinocytes at the dermoepidermal junction as well as dermal mucin deposits are prevalent in both discoid LE and dermatomyositis. In our patient's skin biopsy the perivascular lymphocytic infiltration was more pronounced around the upper dermal vascular plexus and no involvement of hair follicles was observed. Altogether, the histopathologic findings were suggestive for dermatomyositis, especially when correlated with the clinical picture.

The treatment of JDM has not yet been evaluated in randomized controlled trials. Systemic glucocorticosteroids are the mainstay of therapy; they are administered orally (up to 2 mg/kg per day of prednisolone) or as intravenous pulses (usually 30 mg/kg per day of methylprednisolone). Therapy is continued until there is improvement of clinical and laboratory parameters [17]. Corticosteroids may be combined with methotrexate (15 mg/m² once weekly) to allow reduction of cumulative corticosteroid doses and associated side effects [18]. Other therapeutic options include combination of (methyl)prednisolone with azathioprine (1-3 mg/kg in 2-3 daily doses), ciclosporin (3-4 mg/kg in 2 doses adjusted to serum levels [100 ng/ml]), or hydroxychloroquine (5-6.5 mg/kg) [19]. High-dose intravenous immunoglobulins have been administered as adjuvant therapy in steroid-resistant cases [20]. A few case reports have shown disease control by the B lymphocyte-depleting antibody rituximab [21]. Adjunctive measures such as physiotherapy and the use of photoprotective agents may contribute to a better outcome of the disease. In addition, calcium and vitamin D should be administered as co-medication in situations of long-term corticosteroid use.

In conclusion, JDM is a rare but serious autoimmune vasculopathy of childhood that should be diagnosed and treated as early as possible to avoid disability and to minimize life-threatening complications such as systemic calcification, sepsis, hemorrhage, and infarction.

References

1. Pachman LM, Lipton R, Ramsey-Goldman R, Shamiyeh E, Abbott K, Mendez EP, Dyer A, Curdy DM, Vogler L, Reed A, Cawkwell G, Zemel L, Sandborg C, Rivas-Chacon R, Hom C, Ilowite N, Gedalia A, Gitlin J, Borzy M. 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 Apr 15;53(2):166-72. [PubMed]

2. Pachman LM, Jonasson O, Cannon RA, Friedman JM. Increased frequency of HLA-B8 in juvenile dermatomyositis. Lancet. 1977 Dec 10;2(8050):1238. [PubMed]

3. Reed AM, Pachman L, Ober C. Molecular genetic studies of major histocompatibility complex genes in children with juvenile dermatomyositis: increased risk associated with HLA-DQA1 *0501. Hum Immunol. 1991 Dec;32(4):235-40. [PubMed]

4. Mamyrova G, O'Hanlon TP, Monroe JB, Carrick DM, Malley JD, Adams S, Reed AM, Shamim EA, James-Newton L, Miller FW, Rider LG; Childhood Myositis Heterogeneity Collaborative Study Group. Immunogenetic risk and protective factors for juvenile dermatomyositis in Caucasians. Arthritis Rheum. 2006 Dec;54(12):3979-87. [PubMed]

5. Pachman LM, Liotta-Davis MR, Hong DK, Kinsella TR, Mendez EP, Kinder JM, Chen EH. TNFalpha-308A allele in juvenile dermatomyositis: association with increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications. Arthritis Rheum. 2000 Oct;43(10):2368-77. [PubMed]

6. Rider LG, Artlett CM, Foster CB, Ahmed A, Neeman T, Chanock SJ, Jimenez SA, Miller FW. Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies. Clin Exp Immunol. 2000 Jul;121(1):47-52. [PubMed]

7. Koch MJ, Brody JA, Gillespie MM. Childhood polymyositis: a case-control study. Am J Epidemiol. 1976 Dec;104(6):627-31. [PubMed]

8. Pachman LM, Hayford JR, Hochberg MC, Pallansch MA, Chung A, Daugherty CD, Athreya BH, Bowyer SL, Fink CW, Gewanter HL, Jerath R, Lang BA, Szer IS, Sinacore J, Christensen ML, Dyer AR. New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis. Arthritis Rheum. 1997 Aug;40(8):1526-33. [PubMed]

9. Bowles NE, Dubowitz V, Sewry CA, Archard LC. Dermatomyositis, polymyositis, and Coxsackie-B-virus infection. Lancet. 1987 May 2;1(8540):1004-7. [PubMed]

10. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. [PubMed]

11. Spencer-Green G, Crowe WE, Levinson JE. Nailfold capillary abnormalities and clinical outcome in childhood dermatomyositis. Arthritis Rheum. 1982 Aug;25(8):954-8. [PubMed]

12. Huang JL. Juvenile dermatomyositis associated with partial lipodystrophy. Br J Clin Pract. 1996 Mar;50(2):112-3. [PubMed]

13. Kasteler JS, Callen JP. Scalp involvement in dermatomyositis. Often overlooked or misdiagnosed. JAMA. 1994 Dec 28;272(24):1939-41. [PubMed]

14. Pachman LM. Juvenile dermatomyositis. Pathophysiology and disease expression. Pediatr Clin North Am. 1995 Oct;42(5):1071-98. [PubMed]

15. Eisenstein DM, Paller AS, Pachman LM. Juvenile dermatomyositis presenting with rash alone. Pediatrics. 1997 Sep;100(3 Pt 1):391-2. [PubMed]

16. Brown VE, Pilkington CA, Feldman BM, Davidson JE; Network for Juvenile Dermatomyositis, Paediatric Rheumatology European Society (PReS). An international consensus survey of the diagnostic criteria for juvenile dermatomyositis (JDM). Rheumatology (Oxford). 2006 Aug;45(8):990-3. [PubMed]

17. Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet. 2008 Jun 28;371(9631):2201-12. [PubMed]

18. Ramanan AV, Campbell-Webster N, Ota S, Parker S, Tran D, Tyrrell PN, Cameron B, Spiegel L, Schneider R, Laxer RM, Silverman ED, Feldman BM. The effectiveness of treating juvenile dermatomyositis with methotrexate and aggressively tapered corticosteroids. Arthritis Rheum. 2005 Nov;52(11):3570-8. [PubMed]

19. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003 Sep 20;362(9388):971-82. [PubMed]

20. Manlhiot C, Tyrrell PN, Liang L, Atkinson AR, Lau W, Feldman BM. Safety of intravenous immunoglobulin in the treatment of juvenile dermatomyositis: adverse reactions are associated with immunoglobulin A content. Pediatrics. 2008 Mar;121(3):e626-30. [PubMed]

21. Schmidt E, Goebeler M. CD20-directed therapy in autoimmune diseases involving the skin: role of rituximab. Expert Rev Dermatol. 2008 Mar;3(3):259-78.

© 2009 Dermatology Online Journal