A 58-year-old previously healthy man presented to the rheumatology clinic with joint pain and swelling and a rash. Sixteen months earlier, he had an episode of diffuse arthralgia that responded to prednisone. His current symptoms started 2 months ago with diffuse joint pain followed by a rash on his trunk, which he attributed to sun exposure. He had no history of fever, weight loss, or oral ulcers.
Examination of the skin revealed brightly erythematous, smooth papules and nodules over the knees, elbows, and dorsal hands and involving the periarticular and periungual skin of his fingers (Figure 1); red-orange dermal papules coalescing into plaques on the upper chest and back (Figure 2); and indurated waxy papules and plaques of the pinnae (Figure 3) and nares. Examination of the joints revealed symmetrical synovitis of the bilateral metacarpophalangeal, wrist, elbow, and metatarsophalangeal joints and tenderness over the bilateral proximal and distal interphalangeal joints.
Smooth papules and nodules over the fingers.
Brightly erythematous papules coalescing into plaques on the chest and upper back.
Waxy papules of the external ear.
Laboratory testing showed normal results for the sedimentation rate and C-reactive protein; total white blood cell count, platelets, and hemoglobin; and transaminases and creatinine. Mycobacteria tuberculosis interferon-gamma release assay was negative. Lactate dehydrogenase was 332 U/L (reference range 121–224). Peripheral blood smear showed monocytosis, with 11% circulating monocytes (2%–8%); flow cytometry did not reveal a T-cell or B-cell clonality.
Biopsy of a dermal nodule was done, and histopathologic study showed epithelioid histiocytes (CD68+) and scattered giant cells with pink cytoplasm with a ground-glass appearance; periodic acid-Schiff and acid-fast bacteria staining were negative. Radiography of the hands and feet did not reveal inflammatory changes or erosions.
The patient was started on prednisone 20 mg daily, and, based on the likely diagnosis of multicentric reticulohistiocytosis, he was referred to oncology to evaluate for an underlying malignancy; this evaluation was negative. He had incomplete relief with prednisone, and methotrexate 20 mg/week subcutaneously was added, which caused transaminitis. The methotrexate dose was reduced to 12.5 mg/week subcutaneously, and infliximab 5 mg/kg every 8 weeks and alendronate 70 mg/week were added. Prednisone was tapered after improvement in the skin changes and joint pain were observed.
SKIN AND JOINT FINDINGS SUGGEST THE DIAGNOSIS
Multicentric reticulohistiocytosis is a rare disorder of unknown etiology characterized by histiocytic proliferation that leads to papulonodular skin lesions and destructive arthropathy.1 The onset is insidious, and symptoms may start in the skin or the joints. The typical clinical findings involving skin and joints should alert clinicians to this rare diagnosis.
The primary effector cells in multicentric reticulohistiocytosis are reticulohistiocytes, a pathologic population of myeloid-derived tissue macrophages that originate in the bone marrow, circulate as monocytes in peripheral blood, and then infiltrate skin and synovium.1 In these target tissues, they transform into characteristic mononucleate or multinucleate cells with a ground-glass appearance. Smooth, nontender papules may arise over extensor surfaces, with a predilection for the ears and nose, or around nails. Periungual papules may result in a “coral bead appearance.” Skin findings may be notably photodistributed, as was observed in our patient.2
Affected joints in multicentric reticulohistiocytosis include the knees, shoulders, hips, and elbows as well as joints in the spine, feet, ankles, hands, and wrists. Fairly unique to multicentric reticulohistiocytosis is inflammatory involvement of the distal interphalangeal joints.1,2 A disabling arthritis may progress rapidly in the early stages and then become less active over the following 8 to 10 years.1 Arthritis mutilans may occur in about half of patients.
Rarer organ involvement includes the pericardium, pleura, urinary tract, and liver, as well as oral, pharyngeal, eyelid, and nasal epithelia. Systemic symptoms include weight loss, fever, and subjective weakness. Overexpression of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6 in inflammatory lesions and synovial fluid with monocytes expressing an osteoclastic phenotype (receptor activator of nuclear factor kappa B ligand [RANKL] pathway) has been reported.3,4 Multicentric reticulohistiocytosis may coexist with malignancy (25%) or systemic autoimmune disorders (eg, lupus, rheumatoid arthritis, Sjögren syndrome).2
The differential diagnosis of the skin papules includes xanthomas, ie, deposition of lipid-laden histiocytes, and lepromatous leprosy, which is characterized by bacilli-filled macrophages and a grenz zone.5
Reported treatment options include glucocorticoids, methotrexate, leflunomide, azathioprine, hydroxychloroquine, cyclophosphamide, cyclosporin A, tocilizumab, zoledronic acid, alendronate, and tumor necrosis factor inhibitors.2
DISCLOSURES
The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.
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