Juvenile dermatomyositis (DM) is a multisystem disease characterized by nonsuppurative inflammation of striated muscle, skin and the gastrointestinal tract, and also characterized early in its course by an immune complex vasculitis and, later, the development of calcinosis¹⁾. Although the etiology of juvenile DM remains unclear, it is suggested that IgE can be associated with autoimmune diseases, such as systemic lupus erythematosus (SLE) and juvenile DM, by mediating the release of chemical mediators and by faciliating the local deposition of immune complexes²⁾. Intercurrent infections with elevated serum IgE level during the course of the disease give rise to problems in patients with juvenile DM. Atopic dermatitis, or development of calcinosis, may contribute to this problem^3,4). HIE also has the characteristic findings of recurrent infections of the skin and sinopulmonary tract and high serum IgE level. Other findings of HIE include eosinophilia, presence of anti-S.aureus specific IgE, defect of neutrophil chemotaxis, poor delayed hypersensitivity responses and eczematoid dermatitis⁵⁾. Herein, we describe a patient with juvenile DM complicating HIE.

A 13-year-old girl was admitted to the hospital because of multiple skin abscesses. Six years before admission, juvenile dermatomyositis was diagnosed at another hospital on the basis of symptoms of proximal muscle weakness, abnormal findings of muscle biopsy, elevated serum muscle enzyme and skin rash on her face. She had not been managed with regular follow-up. There was a history of recurrent skin infections, pneumonia and eczematous dermatitis over the whole body after the diagnosis of juvenile dermatomyositis. She denied any history of allergic diseases. There was no family history of specific diseases. The temperature was 38.0°C, the pulse was 116 and the respirations were 24. The blood pressure was 90/50 mmHg. On physical examination, the skin of her entire body showed multiple hyperpigmented lesions, lichenoid patches and eczemaoid confluent plaques. Oral thrush and subcutaneous cold abscesses of the left upper eye lid, back and right lower quadrant abdomen were found (Fig. 1). No lymphadenopathy was observed. The lungs were clear. Both knee joints had flexion contractures with muscle atrophy. The following laboratory findings were recorded: hemoglobin 10.5gm/dl, white blood cell count 15,000/mm³ (88,3% neutrophils, 6.6% lymphocytes, 3.5% monocytes, 0.2% eosinophils, 1.4% basophils), platelet count 288,000/mm³, erythrocyte sedimentaion rate 68mm/hour (Westergren method), The protein was 6.7g/dl (albumin 3.2g/dl; globulin 3.5g/dl). The values for glucose, urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactic dehydrogenase, aldolase, alkaline phosphatase, bilirubin, calcium, phosphorus, sodium, potasium, chloride and magnesium were normal. Urine analysis was normal except for proteinuria(+). Levels of C3, C4 and CH50 were normal. The tests for antinuclear antibody, rheumatoid factor, VDRL, hepatitis surface antigen, hepatitis C virus antibody and C-reactive protein were negative. Antibodies to Sm, RNP, Ro, La, Jo-1 and ds DNA were not detected. Serum immunoglobulin examination revealed normal IgG (1,970 mg/dl; normal 800–1,500 mg/dl), IgM (111 mg/dl; normal 45–150 mg/dl), elevated IgA (455 mg/dl; normal 90–325 mg/dl) and IgE (6,650 mg/dl; normal <200 mg/dl). Follow-up serum IgE levels decreased with the treatment of S. aureus infection, but still remained high (3,180 mg/dl, 3,120 mg/dl). Immunoelectrophoresis of serum revealed no evidence of paraproteinemia. Radiographs of the abdomen and both lower extremities showed multiple soft tissue calcifications. EMG and muscle biopsy findings were compatible with inflammatory myopathy (Fig. 2). Antibodies to S. aureus of the IgE class were detected by direct ELISA method, as previously described, with some modifications⁶⁾ (Fig. 3). The result of a delayed hypersensitivity skin test to purified protein derivative, tetanus, diphteria, streptococcus, candidia, trichophyton and proteus was negative. Radioallergosorbent tests to common allergens were negative except for Penicillium notatum. Bacteriologic cultures from skin abscesses were positive for S. aureus. Cultures from oral mucous lesion grew Candida albicans. The total numbers of T cells, T cell subpopulations (CD4+/CD8+) were within normal limits. The Nitroblue-Tetrazolium-test was normal. In vitro lymphocyte proliferation was normal exposure to nonspecific antigens (phytohemagglutinin, phorbol myristate acetate plus ionomycin). The polymorphonuclear leukocyte motility, assessed in a reversible Boyden chamber with fmet-leu-phe and patient’s serum as chemo-attractants, as prevoiusly described⁵⁾, was impaired. She was successfully managed with surgical drainage and antibiotics.

Some diseases, including chronic granulomatous disease, Wiskott-Aldrich syndrome, icthyosis vulgaris, severe combined immunodeficiency and HIE, have similiar clinical findings of recurrent skin infections⁷⁾. This patient was diagnosed as having HIE on the basis of recurrent infections of skin and pulmonary, extremely elevated levels of serum IgE and presence of anti-S.aureus specific IgE, chemotactic defect of neutrophile, eczematoid dermatitis and normal nitroblue tetrazolium test. The late onset of her recurrent infection and normal eosinophil count were atypical. But these have been observed in other reports⁵⁾. S.aureus and C.ablicans were isolated from skin cold abscesses and oral cavity, respectively, in this case. These organisms are known to be most predominant pathogens in recurrent infections of HIE⁵⁾. S. aureus infection with elevated serum IgE is rarely observed in juvenile DM, and this can be partially explained by the previous two reports. First, atopic dermatitis, which is frequently accompanied by S. aureus, has a higher tendency for developing juvenile DM³⁾. Second, the development of calcinosis and granulocyte chemotactic defect in juvenile DM is associated with staphylococcal infections⁴⁾. The causes of recurrent skin infections of S. aureus in this patient are presumed to have a somewhat different mechanism from those two. Hochreutener et al suggested that increased S. aureus specific IgE level, decreased S. aureus specific IgA level, diminished chemotaxis and soft tissue abscesses can be differential points between atopic dermatitis and HIE, but chemotactic defect and anti-S.aureus specific IgE were found to be not only HIE but also atopic dermatitis^8,9). So, sometimes, it may be hard to differentiate HIE from atopic dermatitis in a patient with juvenile DM who has elevated IgE level and S.aureus infection. Differential diagnosis is important because treatment and prognosis is different. Atopic dermatitis does not have recurrent infections of the sinopulmonary tracts and peculiar cold abscesses and has a dermatitis that differs in character and distribution from lesions of HIE⁵⁾. This patient denied any history of allergy, and RAST(radioallergosorbent test) to common allergens, except for Penicillium notatum, were negative. Moore et al emphasized the relationship between the development of calcinosis and recurrent staphylococcal infections with raised IgE in juvenile DM⁴⁾. Although the level of serum IgE in Moore’s cases are elevated, most of them do not meet the definition of HIE (≥2,000 IU/ml). But this patient had extremely elevated IgE level (6,600 IU/ml) during infection and had constantly raised serum IgE levels(≥3,000 IU/ml) during follow-up. Anti-S.aureus specific IgE was detected only during S. aureus infection in this case. Calcinosis occurs commonly with scleroderma, as well as dermatomyositis, and rarely in association with SLE¹⁰⁾. HIE has been rarely reported in patients with SLE^11–13), but these cases had no association with calcinosis. Calcinosis develops in up to half the patients with juvenile dermatomyositis¹⁾. It must be clarified whether recurrent skin infection with elevated IgE occurs in most juvenile DM patients with calcinosis or not. Although the immunologic basis of elevated serum IgE in patients with HIE has not been defined, a deficiency of suppressor T cell to inhibit IgE production⁵⁾, imbalances between IL-4 producing and IFN-γ producing helper T cells¹⁴⁾ and decreased metabolism of IgE¹⁵⁾ seem to be responsible for elevated levels of IgE. There were reports that CD8+ to CD4+ ratio was reduced in a patient with juvenile DM¹⁶⁾. But this was not found in our case. The causes of susceptibility to infections have not been documented. Schopfer et al suggest that histamine is released on crosslinkng of mast cell-bound antistaphylococcal IgE by staphylococcal antigens and interferes with the activity of polymorphonuclear leukocytes, resulting in the failure of effective S. aureus clearing¹⁷⁾. It is known that there is variability in both HIE and juvenile DM patient’s neutrophil and monocyte chemotaxis⁵⁾. Whether the neutrophils were intrinsically abnormal or not was inconclusive in a patient with HIE, but chemotactic defect of neutrophil to fmet-leu-phe and patient’s serum as chemo-attractants was observed in this case. HIE has significantly lower proportions of circulating T cells that can produce IFN-γ and TNF-α, in comparison with normal controls, which also may contribute to recurrent infections¹⁴⁾. In conclusion, similar findings, including elevated serum IgE, arti-S.aureus IgE and chemotactic defect of neutrophil, can be found in patients with HIE, juvenile DM and atopic dermatitis. HIE must be considered in the differential diagnosis of a patient with juvenile DM who has an elevated level of IgE and staphylococcus aureus skin infection. It will be interesting to define whether the underlying mechanism is the same or not in these diseases.