Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal nail fold capillaries, interstitial lung disease, Raynaud's phenomenon, esophageal dysmotility, and positivity for rheumatoid factor and anti-SSA antibodies. She developed massive inflammatory changes of the cutis, the subcutis, and the muscle fasciae of the right leg, that after several failed attempts of immunosuppressive treatments were found to be caused by Mycobacterium intracellulare. While she was receiving high-dose prednisolone, as worsening of her connective tissue disease was suspected to be the cause of the inflammatory changes, she had Listeria monocytogenes meningitis and was hospitalized for several weeks, but she recovered from this without sequelae. After Mycobacterium intracellulare infection was diagnosed, she was treated with clarithromycin and rifampicin. Her skin manifestations, arthralgias, and fatigue improved considerably, and the wounds of the right leg healed, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma.


Introduction
We describe a patient with scleroderma who developed patchy, indurated elements of her skin, fasciitis, and arthritis that was long thought to represent activity of her rheumatic disease that had long been hard to classify. e manifestations progressed despite therapy with high-dose prednisolone. Skin biopsy showed granulomatous in ammation caused by Mycobacterium intracellulare. Remarkably, she had progression of scleroderma in parallel with mycobacterial infection that mimicked cutaneous manifestations of connective tissue disease.

Case Presentation
is patient developed thickened and painful ngers, dyspnea, arthritis of the knees, and a painful swelling dorsal to the right knee with redness of the skin at age 41 years. She had a history of myalgias with elevated C-reactive protein but with normal creatine kinase and a painful necrotic wound at the medial malleolus of her left ankle in the preceding years; these problems had responded well to prednisolone and le unomide as steroid-sparing agent. Deep venous thrombosis was excluded with ultrasonography. A high-resolution CT scan of the lungs showed subpleural reticulation mainly of the lower lobes, discrete ground glass changes, and traction bronchiectasis. She had low forced expiratory volume after one second, 2.5 L (77% of expected), and low total lung capacity, 4.7 L (82% of expected), but normal alveolar volume-corrected carbon monoxide di usion, 1.5 mmol/min/kPa/L (93% of expected). Bronchoalveolar lavage and transbronchial biopsies showed no fungal infection. Hep-2 cell anti-nuclear antibody testing showed a nuclear speckled pattern, and anti-SSA antibodies were present in high titer. She had eosinophilia, 0.52 × 10 9 /L, and elevated immunoglobulin G (IgG), 33 g/L. e skin elements of the right leg progressed, as did the tightness of the skin of her ngers. On low suspicion of erysipelas or Lyme disease, she was treated with benzylpenicillin and doxycycline without e ect. Scleroderma, eosinophilic fasciitis, and systemic lupus erythematosus were considered. A skin biopsy of the right leg showed deep subcutaneous and fascial in ammation, both perivascular and panniculitis, with nodular lymphocytic in ltrates, many plasma cells, a few eosinophils, and a few granulomas. It was judged compatible with, but not speci c for, eosinophilic fasciitis. A bone marrow biopsy showed hyperplastic myelopoiesis similar to what had been observed years earlier.
Radiography of the esophagus showed dysmotility of the lower third compatible with scleroderma. e arthralgias in knees and shoulders worsened, and she developed livedo reticularis, malaise, and loss of appetite.
Methotrexate was prescribed, but the skin elements worsened, and she was admitted with abdominal pain. Enlarged mediastinal and axillary lymph nodes were found by computed tomography. In ammatory bowel disease was searched for but dismissed after gastroscopy, colonoscopy, and magnetic resonance imaging (MRI) of duodenum and jejunum. Severe Candida esophagitis was diagnosed and treated. en, while on prednisolone 22.5 mg qd, she was hospitalized because of Listeria monocytogenes meningitis for three weeks, but she recovered from this without sequelae.
At age 43 years, MRI ( Figure 1) showed considerable in ammatory changes along the fasciae of all muscles of the distal right thigh and severe subcutaneous contrast enhancement. At this stage, over a year after the rst hard skin elements of the right lower leg had emerged, the skin changes had progressed from the lower leg up through the thigh, and the clinical presentation of the patient was suggestive of an infectious etiology (Figure 2).
A repeated skin biopsy revealed severe granulomatous in ammation of epithelioid cells with small necroses.
e Ziehl-Neelsen stain showed acid-fast bacilli, and culturing identi ed them as Mycobacterium intracellulare, one of the two species of Mycobacterium avium complex (MAC) within the group of nontuberculous mycobacteria. A PET-CT scan (Figure 3) showed pronounced in ammatory cutaneous changes of almost the whole right leg with possible muscular involvement, patchy in ammatory changes of the muscles and skin of the left leg, lymphadenitis of the inguinal and iliac lymph nodes, and minor skin changes of the right upper arm similar to those of the right leg.
She responded well to 12-month treatment with clarithromycin and rifampicin, the swelling of the leg diminished gradually, her arthralgias and malaise   Case Reports in Rheumatology improved, and the wounds of her right leg healed slowly, unfortunately with signi cant scarring. One year after nishing this treatment, she was feeling well and had no signi cant dyspnea or di culty swallowing, but the skin changes of her ngers compatible with scleroderma persisted and SSA antibodies remained high-titer positive, while anti-RNA-polymerase III, anti-centromere, and anti-SCL-70 antibodies were negative.

Discussion
Scleroderma was judged as a reasonable diagnosis based on her pu y ngers that developed into sclerodactyly, abnormal nail fold capillaries, Raynaud's phenomenon, interstitial lung disease, and lower esophageal dysmotility [1]. We wondered why she contracted two rather unusual pathogens, Listeria and Mycobacterium, that share the propensity to live inside the host's cells and are guarded against by the cellular immune response [2,3]. Immunede ciency testing showed normal levels of immunoglobulins, normal vaccination response to diphtheria and tetanus, low levels of CD8-positive T cells, normal levels of CD4-positive T cells and NK cells, and normal IL-12 and interferon-γ signalling [4]. e immunosuppressive treatments and the presence of an autoimmune disease were possible causal factors. is case report demonstrates that Mycobacterium intracellulare infection is a possible di erential diagnosis when a patient with established scleroderma has cutaneous manifestations that are unusually severe and progressing despite immunosuppressive therapy.