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].