An Unusual Case of Juvenile Dermatomyositis Complicated by Macrophage Activation Syndrome

Juvenile dermatomyositis (JDM) is a well-known autoimmune disorder presenting with proximal muscle weakness and typical cutaneous features. Macrophage activation syndrome (MAS), a severe, life-threatening hyperinflammatory state, which represents secondary hemophagocytic lymphohistiocytosis. It usually emerges in acute exacerbations of autoimmune rheumatic disorders, malignancies, infections, and drugs, but remains infrequently reported in association with JDM. This case report describes an unusual case of MAS in a teenage girl with dermatomyositis (DM), highlighting the challenges in diagnosis and management. A 16-year-old girl presented with a 6-month history of joint pains and generalized weakness. She was undergoing evaluation for polyarthralgia and recently started on etoricoxib and vitamin D supplements. During the last 15 days, she had suddenly developed oral, ocular, and genital mucosal erosions with crusting along with reddish-brown skin rash over the body (Figure 1a). At first, she was suspected of having developed Stevens-Johnson syndrome (SJS) and was admitted to the ward. Examination revealed extensive mucosal ulcers with hemorrhagic crusting, poikiloderma vasculare atrophicans with vesiculation and superficial desquamation (Figure 1b). Heliotrope rash, Gottron's papules, and bilateral proximal muscle weakness in both limbs were also noticed. Dermoscopy revealed reticulate hyperpigmentation, white structureless atrophic areas with background erythema, and telangiectasias (Figure 1c). Nail-fold capillaroscopy showed ragged cuticles, capillary dropouts, an irregular capillary network, and prominent subpapillary-plexus (Figure 1d). Lab investigations reported raised muscle enzymes (Table 1), positive antinuclear-antibodies (4 + speckled pattern) along with Anti-U1-RNP antibodies. Electromyography (EMG) and magnetic-resonance imaging (MRI) of proximal girdle muscles demonstrated myopathic changes (Table 1). Skin biopsy revealed focal detachment of the stratum corneum, a few necrotic keratinocytes, hyperkeratosis, parakeratosis with basal layer degeneration and spongiotic epidermis, along with perivascular lymphohistiocytic infiltrate and melanophages, corresponding to the clinical presentation. While muscle biopsy was denied by the parents, an MRI of the muscles suggested myositis. A diagnosis of juvenile DM (poikilodermatous and vesiculobullous variant) was rendered based on the Bohen & Peter criteria and the EULAR/ACR criteria [1]. The patient's serological tumor markers like CA-125 and beta-HCG were also mildly increased, but no abnormality was detected on clinical and radiological examination. She was started on systemic steroids. Overnight, she experienced acutely worsening muscle weakness, tenderness, disorientation, dyspnea, and chest pain. With signals pointing to an acute pulmonary thromboembolic event, lab tests were run, NT-proBNP (10,014 pg/mL, normal < 207 pg/mL) and D-dimer levels (3530 ng/mL, normal < 390 ng/mL) were found elevated with pancytopenia. Contrast-enhanced computed tomography (CECT) of the chest and two-dimensional echocardiogram (2D-ECHO) were found to be normal. At this point, the possibility of MAS was weighed, which was subsequently confirmed by raised serum ferritin, triglycerides, and aspartate transaminase (AST) levels conforming to EULAR/ACR-2016 criteria [2] (Table 1). She was started on pulse methylprednisolone and rituximab intravenously in view of non-availability and cost constraints associated with other options, to have a prompt suppression of the hyperinflammatory state. There is no standard treatment protocol for MAS management; however, high dose steroids have shown good efficacy, and rituximab has also been used in cases of MAS secondary to systemic lupus erythematosus (SLE) [3, 4]. The patient has attended regular follow-ups at our outpatient department since the event and is in good health. The treatment regime comprising pulse methylprednisolone and rituximab resulted in a quick recovery of her clinical condition and normalcy of lab values. Acute SLE could be a close differential diagnosis, but the lack of a photosensitive rash, serositis, synovitis, systemic organ involvement, the absence of specific antibodies and the presence of typical myopathy and cutaneous features favored dermatomyositis. The clinical presentation also mimicked SJS-TEN initially, but the overall picture resembled JDM, due to non-corraborating drug history, no skin pain, vesicles localized over poikiloderma only and histopathology. Septicemia was excluded by a lack of corroborating changes in blood counts and repeatedly negative blood cultures. The absence of high titres of anti-U1-RNP, synovitis, hand edema, Raynaud's phenomenon, and acrosclerosis ruled out mixed connective tissue disorder. MAS is known to complicate SLE and juvenile idiopathic arthritis among the rheumatic diseases but it's a rare event in the course of JDM. Recent reviews compile the limited cases with varied presentations and high mortality even with different treatment approaches, including steroids, cyclosporin, etoposide, anakinra, cyclophosphamide, and tofacitinib [5, 6]. However, the SJS-like lesions over poikiloderma, raised tumor markers, features of acute thromboembolic events, and improvement on methylprednisolone and rituximab are unique in this case. An SJS-like case was first observed by Holmes in 1948 [7]. Later on, a few polymorphous vesiculobullous lesions were also reported, carrying a risk of underlying malignancy [8]. Therefore, MAS should be suspected promptly in a rapidly deteriorating case of JDM, as it could have significant mortality if not diagnosed and managed in a timely manner. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.