Juvenile Dermatomyositis
JDM is a rare inflammatory myopathy and vasculopathy, with an incidence of 0.2-0.4 per 100,000 children [46-48]. Peak incidence occurs from 5-10 years of age, with a female predominance [46, 48, 49]. Clinical manifestations include inflammation of the muscle (proximal weakness) and skin (ulcerations, calcifications, Gottron’s rash, heliotrope rash, nailfold capillary changes), with possible involvement of the lung, gastrointestinal tract, and joints [50]. The incidence of pulmonary involvement in JDM is unknown. Pulmonary manifestations in JDM include respiratory muscle weakness, hypoventilation, impaired swallowing leading to aspiration, impaired airway clearance with respiratory tract infections, spontaneous pneumothorax/pneumomediastinum, pulmonary vasculitis, and interstitial lung disease [51, 52].
While the incidence of ILD in JDM is not clear, it represents a significant source of morbidity and mortality [53, 54]. ILD can present with cough and shortness of breath but can also be seen in asymptomatic patients when identified early. ILD in JDM can be rapidly progressive (progression within 3 months of symptom onset) and can occur before or after myositis symptoms. Serum tests elevated in JDM-related ILD include Krebs von den Lungen 6 (KL-6), molecule that is predominantly expressed by damaged alveolar type II cells, and IL-18. In addition, anti-melanoma differentiation-associated gene 5 (anti -MDA-5) and anti-Ro52 antibodies may appear before signs of interstitial lung disease [53, 55-60].  ILD in adult dermatomyositis has been associated with anti-Jo-1 and anti-synthetase antibodies [61, 62], but these antibodies are rarer in children. If any of these antibodies are present, the patient needs to be followed closely by a pulmonologist for the development of ILD.
PFTs and cross-sectional chest imaging are essential for evaluating for pulmonary involvement in JDM. Patients with JDM can have a range of PFT patterns, which may be due to the presence of ILD or other pulmonary complications. Prior reports show abnormal lung function in a high percentage of patients, including asymptomatic patients [63]. From case series the following PFT abnormalities were reported in JDM: obstructive lung disease,15%, abnormal DLCO, 10 – 49%, reduced TLC, 24 – 29%, decreased maximal respiratory pressures, 30% [51, 63-66].
CT findings in ILD associated with JDM cannot distinguish between rapidly progressive and chronic disease, but this is often apparent based on rate of progressive symptoms. [67] Findings previously reported include atelectasis, nodules/micronodules, ground glass opacities, air trapping, bronchial wall thickening, traction bronchiectasis, reticulation, consolidation, and fibrosis [51, 53, 54]. Biopsies are not necessary for diagnosis of ILD in JDM, but reported pathology includes nonspecific interstitial pneumonia (NSIP), cellular interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia (BOOP), usual interstitial pneumonia (UIP), acute interstitial pneumonitis, diffuse alveolar damage (DAD) and fibrosis [68-76]. Pneumothorax or pneumomediastinum may have a poorer prognosis and complicate ILD in JDM [77].
Early initiation or escalation of immune suppression is critical for ILD given the possibility of severe deterioration. There are no randomized controlled trials for treatment of ILD in JDM. Glucocorticoids and methotrexate with or without immunomodulatory IVIG (1-2g/kg) are the mainstay of treatment for JDM in general [78]. Patients with anti-MDA5 antibody rapidly progressive ILD require rapid escalation of therapy. Case reports/series of ILD associated with JDM have reported efficacy in using calcineurin inhibitors (cyclosporine, tacrolimus) [53, 54, 79], cyclophosphamide, plasmapheresis [67, 80, 81], rituximab [60], and tofacitinib [82-84]. In the most severe cases, some patients have been put on extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant; however, the mortality rate is still very high [67, 80, 81].