On December 2017, a 50-year-old Caucasian woman, previously in good health, developed cutaneous erythematosus papular lesions both on the palmar and dorsal surface of hands and fissuring of the distal fingers, in the absence of other symptoms. She consulted a dermatologist who prescribed topical steroids. Three months later, Raynaud's phenomenon and dryness of the skin appeared. She consulted a rheumatologist who, after laboratory examinations showing antinuclear antibody (ANA) positivity, made the diagnosis of undifferentiated connective tissue disease (UCTD) and prescribed prednisone 25 mg daily with progressive tapering until 12.5 mg daily, with partial improvement. Two months later, she developed arthritis of hands and wrists, alopecia, and worsening of the skin lesions. She consulted another rheumatologist who added hydroxychloroquine 400 mg daily without any improvement. Instead, asthenia, muscle weakness, and pain appeared. For this reason, the rheumatologist prescribed cyclosporine 160 mg daily; hydroxychloroquine was stopped because of the onset of vertigo, which disappeared with drug suspension, while prednisone 12.5 mg daily was continued. On October 2018, because of further worsening of asthenia and myalgia and the onset of mild dyspnea, high-resolution computed tomography (HRCT) of the chest was performed, and it showed initial signs of ILD.
Then, the patient was referred to our attention and she was admitted to our rheumatology ward.
Concerning the medical history, she did not report comorbidities, pregnancies, or miscarriages. She had smoked for ten years, but she was not smoking anymore. She was in menopause from the age of 45. Her family history was unremarkable. At the physical examination, she was afebrile, normotensive, and breathing and cardiac rates were, respectively, 16 times/min and 90 beats/min. Cardiac and abdominal examinations were normal; pulmonary examination showed fine bilateral basal crackles. There were papular erythematosus lesions on both the palmar and dorsal surface of her hands and extensor surface of elbows and concomitant fissuring of the distal fingers (Figure 1). Musculoskeletal examination did not evidence joint tenderness/swelling or deformity, but it revealed a reduction of muscle strength at the four limbs. Laboratory tests showed a mild normochromic, normocytic anemia, a slight increase of aspartate aminotransferase (AST) (52 U/L; normal range <40 U/L) and of lactate dehydrogenase (LDH) (688 U/L; normal range <400 U/L), a modest polyclonal hypergammaglobulinemia, and an increase of C reactive protein (CRP) (10 mg/L; normal range <5 mg/L), while white blood count, platelets, creatinine, electrolytes, erythrocyte sedimentation rate (ESR), uric acid, alanine aminotransferase (ALT), creatine phosphokinase, and urinalysis were normal. Screening for hepatitis B and C virus was negative, while the QuantiFERON-TB Gold test was indeterminate.
A skin right hand biopsy revealed the presence of interface dermatitis, with perivascular inflammatory infiltrate prevalently at the dermoepidermal junction and injury of the basal cells keratinocytes, as it can be observed either in systemic lupus erythematosus (SLE) or in DM.
Electromyography (EMG) of the upper limbs evidenced signs of median neuropathy in the right hand and no other pathological sign.
Muscle magnetic resonance (MRI) of the lower limbs showed diffuse and symmetric oedema of all the muscles of the thigh without fatty degeneration (Figure 2).
Chest HRCT confirmed the presence of bilateral apical pleural thickening and various subpleural, paramediastinal, and basal areas of reticular thickening associated with ground glass lesions. There was no pleural effusion or linfoadenopathy. Spirometry with diffusing capacity for carbon monoxide (DLco) evidenced signs of a disventilatory obstructive syndrome with severe DLco reduction (53% of the predicted value). Echocardiogram was normal.
A nailfold capillaroscopy revealed different alterations such as a disordered loops architecture, capillary enlargement with some megacapillaries, microhaemorrhages, and neoangiogenesis, suggestive of a "scleroderma-like pattern" (Figure 3).
Indirect immunofluorescence (IIF) for ANA showed a cytoplasmic pattern at a titer of 1 : 160; rheumatoid factor, anti-SSA (Ro), anti-SSB (La), anti-Sm, anti-RNP, anti-Jo1, anti-SCL-70, anti-ds DNA, C3, C4, and anti-citrullinated peptide antibody (ACPA) were normal, while a myositis panel immunoblotting test evidenced anti-MDA5 positivity (53 AU; normal range <10).
Therefore, the patient was discharged with a diagnosis of anti-MDA5 DM and ILD. Prescribed therapy was mycophenolate mofetil 2 gm daily and prednisone 25 mg daily associated with a weekly bisphosphonate tablet and a prophylactic therapy for Mycobacterium tuberculosis.
At the follow-up visit, two months later, the patient reported worsening of fatigue, weakness, and dyspnea. Her laboratory exams showed an increase of inflammatory indexes (ESR 50; normal range <30; CRP 15 mg/L; normal range <5 mg/L), while a spirometry evidenced a further DLco reduction (42% of the predicted value).
After consultation with the respiratory physician, we decided to discontinue mycophenolate and start a second-line therapy with RTX 1000 mg on two occasions 2 weeks apart. Prednisone was continued with progressive tapering to 12.5 mg daily.
Patient was re-evaluated two months later. She reported a marked improvement of fatigue, muscle weakness, and dyspnea. At physical examination, the skin lesions had improved. Laboratory tests showed a reduction of ESR and CRP values (ESR 30; normal range <30; CRP 5; normal range <5 mg/L). DLco parameters were significantly ameliorated (from 42% to 56% of the predicted value). Therefore, it was possible to reduce prednisone dosage from 12.5 mg to 10 mg daily.
The patient is currently under follow-up in our unit.