Juvenile dermatomyositis in Thai children: Retrospective review of 30 cases from a tertiary care center

Patient selection

Juvenile dermatomyositis patients seen during January 1994 to November 2019 who were aged <18 years at disease onset and who satisfied the Bohan and Peter criteria for classification^23,24 as definite juvenile dermatomyositis were included.

Retrospective assessment

The following information was collected from the medical records: demographic data, age of onset, age at diagnosis, onset type (progression of the first symptoms to the presentation that fulfilled Bohan and Peter criteria, and characterized as acute if it occurred within one month, subacute if it occurred in 1-3 months, and insidious if it took longer than three months), clinical features, results of investigations, treatment, complications, and outcomes. Disease course was classified as monocyclic if the patient had full recovery within one year after initiation of therapy without any relapse, chronic polycyclic in cases of relapsingremitting disease, and chronic continuous if the patient had persistent active disease for more than one year after diagnosis.¹⁰ Due to the retrospective design of this study, the results described in medical record were reported.

Statistical analysis

Descriptive statistics are expressed as frequency and percentage for categorical variables, as mean ± standard deviation for normally distributed quantitative continuous variables, and as median and range [interquartile range (IQR) or minimum to maximum] for non-normally distributed quantitative continuous variables. Chi-square test, Fisher’s exact test, or independent-samples t-test was used to determine differences between groups. A p-value less than 0.05 was considered statistically significant. SPSS Statistics software (SPSS, Inc., Chicago, IL, USA) was used to perform all statistical analyses.

Demographic data

Thirty cases (22 females and 8 males) diagnosed with definite juvenile dermatomyositis were enrolled in this study. Forty percent of patients presented with their first symptoms at an age less than five years. The median duration from initial symptoms to fulfilling Bohan and Peter criteria was two months (range: 0.5-24 months). No patient had a family history of juvenile dermatomyositis or other connective tissue diseases.

Clinical manifestations

The most common presenting complaints were weakness, rash, and muscle pain in 27/30 (90%), 26/30 (86.7%), and 17/26 (65.4%) of patients, respectively [Table 1]. From patient history, 10 (33.3%) and 11 (36.7%) of patients presented with a rash that occurred before and concomitant with muscle weakness, respectively. In this study, most patients (27/30, 90%) had muscle weakness. Proximal muscle weakness affecting the limb-girdle and/or the neck flexor muscles accounted for most of the presenting symptoms in patients with muscle weakness. There was no case of amyopathic dermatomyositis in this study. There were 3 (10%) cases without clinically significant muscle weakness; however, all of those three patients had classic cutaneous features, abnormal muscle enzymes, EMG, and/or relevant changes on muscle biopsy.

The cutaneous findings observed in our patients are shown in Table 2. Thirty percent of patients who reported pigmentary changes had post-inflammatory hypo- or hyperpigmentation after resolution of active cutaneous lesions. We did not find any poikilodermatous changes.

Constitutional symptoms, such as fever, weight loss and poor appetite were found in less than 30% of patients. Gastrointestinal involvement included hepatomegaly, diarrhea, and swallowing difficulty, in 4/30 (13.3%), 2/25 (8%) and 2/29 (6.9%) of patients respectively. We found only 1/29 (3.4%) of patients presenting with dysphonia and dyspnea.

Investigations

The results of related investigations are shown in Table 3. EMG in 11 of 13 (84.6%) patients revealed myopathic changes and muscle membrane irritability consistent with inflammatory myopathy. Muscle biopsy was performed in 19 cases, and 17 of them (89.5%) demonstrated mononuclear cell infiltration in the perimysium and blood vessels with extension into perifascicular muscle fibers, and coexisting perifascicular atrophy. MRI was performed in only two cases, both of which showed muscle swelling and atrophy consistent with myositis. Myositis-specific antibodies testing was performed in 18 cases. Of those, 5 (27.8%) patients were positive, with one each of anti-nuclear matrix protein 2 (NXP2) antibody, anti-melanoma differentiation-associated protein 5 (MDA5) antibody, anti-Ku, anti-Jo1 and anti-signal recognition particle (SRP) antibody.

Treatment

Rashes were treated with topical corticosteroids in most (19/20, 95%) patients, and low to moderate potency topical corticosteroids were used in most (18/19, 94.8%) of these. Topical calcineurin inhibitors were prescribed in 5/20 (25%) of patients (pimecrolimus in 5%, and tacrolimus in 20%). Photoprotection and sunscreens were recommended in all patients.

Systemic corticosteroids were the mainstay of therapy (26/27, 96.3%), and 22.2% of patients received corticosteroids monotherapy. Pulse intravenous methylprednisolone (30 mg/kg/dose) for 1-3 days was prescribed initially in 13 (48.1%) of 27 patients with severe clinical presentations such as severe myositis or respiratory involvement, and that treatment was followed by tapered oral prednisolone. The median initial prednisolone dose was 2 mg/kg/day (range, 0.4-2 mg/kg/day). Twenty-one (77.8%) of 27 patients were concurrently started on additional immunosuppressive medications. A combination of prednisolone and methotrexate was the most common regimen used (20 patients, 74%), with a mean methotrexate dose of 0.5 ± 0.1 mg/kg/week. Cyclophosphamide was used in three patients, two with respiratory failure from rapidly progressive interstitial lung disease, and one patient with refractory weakness and dermatitis despite a combination of immunosuppressive agents including prednisolone, azathioprine and cyclosporin. Other immunosuppressive drugs included mycophenolate mofetil (5/27, 18.5%), intravenous immunoglobulin (3/27, 11.1%), cyclosporin (1/27, 3.7%) and azathioprine (1/27, 3.7%). Antimalarial drugs were used in 18/27 (66.7%) patients. Hydroxychloroquine was the most commonly used anti-malarial with an average dosage of 4.5 ± 0.7 mg/kg/day.

Clinical outcomes, complications, and course of disease

The mean follow-up period was 3.1 years (range, 0-18.5 years). Three of the patients were followed up less than 1 years. The disease course of 30 patients was classified as monocyclic, chronic polycyclic, and chronic continuous type in 9 (33.0%), 8 (26.7%), and 7 (23.3%) patients, respectively. The disease course in this study and in other published studies is presented in Table 4. Serum alanine aminotransferase, aspartate aminotransferase, creatine kinase values returned to their normal levels in mean durations of 1.1, 1.5, 1.6, and 9.3 months respectively, after the start of treatment.

Side effects of systemic and topical corticosteroids were detected in 12/24 (50%) of patients, including cushingoid appearance (8/24, 33.3%), acneiform eruption (4/23, 17.4%), cataract (3/23, 13%), osteoporosis (2/23, 8.7%), and glaucoma (1/23, 4.4%). One patient developed severe osteoporosis and vertebral compression fracture. No patients developed other connective tissue diseases or overlap syndromes during the follow-up period. Side effects of immunosuppressive drugs were mostly transient hepatitis (one patient) and renal insufficiency (one patient, three years after receiving methotrexate). After discontinuation of the medication, all the abnormalities returned to be normal. One patient developed methotrexate-induced liver fibrosis confirmed by fibroscan.

Calcinosis cutis was found in 6/28 (21.4%) of juvenile dermatomyositis patients, and statistically strongly correlated with increased duration of illness before diagnosis (p=0.008). Those with calcinosis cutis had had their illness for a median duration of 1.8 years (range, 0.6-6 years) before diagnosis. In contrast, patients who did not have calcinosis cutis had their illness for a median duration of only 0.45 years (range, 0.06-7 years) before diagnosis. Two patients with calcinosis cutis received bisphosphonate therapy. One of those patients improved after two courses of pamidronate, but the other patient was given both diltiazem and pamidronate and had no significant improvement. Extraskeletal osteosarcoma in long-standing calcification was observed in one of the six patients with calcinosis cutis in this study. The diagnosis was made 12 years after disease onset. At the time of diagnosis, she had already developed multiple calcified lesions that resulted in flexion contractures of the elbows, and metacarpophalangeal and interphalangeal joints of the hands. Despite aggressive treatment including intravenous pulse methylprednisolone, oral prednisolone and methotrexate, her disease intermittently relapsed. Calcinosis cutis was treated with diltiazem and bisphosphonate for one year, but there was no improvement; only progression was observed. Twelve years after disease onset, she developed a progressively enlarging mass at the left thigh. Soft tissue X-ray of the thighs showed a huge soft tissue mass with internal amorphous calcifications [Figure 1]. Tissue biopsy revealed a high-grade extraskeletal osteosarcoma without vascular or nerve invasion [Figures 2, 3, and 4]. Left hip disarticulation was then performed. This patient continues to be treated for juvenile dermatomyositis and wears a limb prosthesis.

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Figure 1:

Huge soft tissue mass at left proximal thigh with internal amorphous calcifications. Femoral cortex preserved.

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Figure 2:

Huge deep-seated soft tissue mass at anterolateral aspect of left proximal thigh with heterogeneous tan-white tumor tissue, gritty calcifications, tumor necrosis, and cystic change. No femoral cortex invasion.

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Figure 3:

The tumor is composed of spindle and polygonal cells producing trabecular osteoid (left lower) and bone matrix (right upper). (H&E, 100x)

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Figure 4:

The tumor cells contain enlarged atypical nuclei with coarse chromatin and prominent nucleoli. Mitotic figures are frequently observed. (H&E, 600x)

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Three (16.6%) of 18 patients presented with joint deformity at the time of diagnosis. The elbow and knee joints were the common sites of joint contracture in the patients. One of our patients also involved the small joints of the hands including metacarpophalangeal and proximal interphalangeal joints. The mean duration of illness before diagnosis in these patients was 1.8±0.9 years. Joint deformity was found to be significantly correlated with abnormal muscle enzyme levels (p=0.02).

The mortality rate was 11.1% (3/30 patients) in this study. One patient died from respiratory failure despite aggressive therapy including pulse methylprednisolone, and intravenous immunoglobulin. Two severe juvenile dermatomyositis cases had respiratory failure and were treated with pulse intravenous cyclophosphamide (500 mg/m²/dose), and one of those patients received extracorporeal membrane oxygenation (ECMO) and plasmapheresis. Ultimately, both of those patients succumbed to sepsis and aspiration pneumonia.

Limitations

The retrospective design of our study renders it vulnerable to incomplete or missing data. Second, this was a single-center study. Third, our center is Thailand’s largest national tertiary referral center, and our findings may not be generalizable to other care settings. Finally, our sample size was small due to the relative rarity of this disease. Future prospective multicenter studies and/or meta-analyses are needed.