LAUSR

Dear Editor, We would like to present a fatal case of macrophage activation syndrome (MAS) that developed in the early phase of an initially mild dermatomyositis with antiJo-1 antibody in a 53-year-old female patient. Our goal is to increase the awareness of this life-threatening condition associated occasionally also with autoimmune diseases, sometimes even at the initial phase of their clinical presentation. Correct diagnosis and rapid treatment of this condition is of critical importance for the outcome. MAS, or an acquired or secondary hemophagocytic lymphohistiocytosis (HLH), is a rare life-threatening disorder resulting from an uncontrolled immune inflammatory response secondary to many other conditions, including viral, bacterial, fungal or parasitic infections, malignancy (mainly hematologic) or autoimmune diseases. Its pathogenesis is linked to the exaggerated and uncontrolled activation of macrophages with prominent bone marrow and other reticuloendothelial system hemophagocytosis. In our patient the first symptoms of an autoimmune disease appeared 6 months earlier as a Raynaud’s phenomenon, progressive proximal skeletal muscle weakness, morning stiffness, arthralgias and arthritis (wrists, hands and knees), fatigue, anorexia and weight loss; skin changes were not observed. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies and the indirect immunofluorescence screening test for antinuclear antibodies were interpreted as negative; creatine kinase and myoglobin levels were not checked. Initial diagnosis of reactive arthritis was made and the patient was treated with low dose methylprednisolone (8 mg/day) with a rapid clinical improvement. Five months later, while still on the same dose of steroids, symptoms reappeared again and were accompanied by high fever and large erythematous elevated skin rash localized on thighs, forearms and trunk. The patient was empirically treated with antibiotics with no improvement, and finally transferred to our University Hospital. On admission, apart from the skin lesions, high fever (39°C) and sinus tachycardia were observed. Results of some relevant laboratory tests are given in Table 1. Peripheral lymphadenopathy was not observed, but lung computed tomography (CT) scans revealed enlarged mediastinal lymph nodes with no other abnormalities. Abdominal CT was normal. Spirometry showed a mild, irreversible obstructive pattern (the patient was an ex-smoker) with normal total lung capacity in body pletysmography. Blood, sputum, throat swab and urine microbiological cultures were negative, as well as serological tests for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, cytomegalovirus and Epstein–Barr virus. Toxoplasmosis, toxocarosis, brucellosis, syphilis, and Lyme borreliosis were also excluded based on serology, microbiological cultures and molecular diagnostic. Bronchoalveolar lavage fluid (BAL) showed 96% of macrophages; many of them hemosiderin-laden. Microbiological and molecular tests of BAL excluded active lung infection of Mycobacteria, cytomegalovirus, Chlamydia pneumonia, aspergillus, candida and Pneumocystis jiroveci. Skin changes on ultrasonography presented subcutaneous edema. Skin biopsy on histopathology showed orthokeratotic epidermis and dermal edema, with mild lymphoid infiltrates in the perivascular compartment. Muscle biopsy (biceps brachii) revealed mild endomysial lymphocyte infiltration, degeneration and atrophy of muscle fibers with single necrotizing muscle fibers. Screening indirect immunofluorescence test for antinuclear antibodies (HEp-2 line; Euroimmun Medizinische Labordiagnosika AG, L€ ubeck, Germany) was slightly positive (titer of 1 : 160) but Euroline Myositis Profil 3 (Euroimmun Medizinische Labordiagnosika AG, L€ ubeck, Germany) revealed presence of anti-histidyl-tRNA synthetase (anti-Jo-1) antibodies. The diagnosis of dermatomyositis with atypical skin changes was made and 10 days after admission high doses of steroids (four 500 mg methylprednisolone