Multicentric reticulohistiocytosis (MRH)
MRH is a rare disease with prominent skin and joint manifestations that is classified among the non-Langerhans cell histiocytoses. It affects women more than men (3:1), most commonly in the fourth decade. Most patients have symmetric polyarthritis. The cutaneous manifestations occur after a mean of 3 years (66%), although in one-third of patients, the skin lesions will occur before or simultaneously with the arthritis. Systemic manifestations including fever, weight loss, and fatigue commonly occur. Pulmonary, cardiac, and myopathy symptoms can occur.
How does the arthritis of MRH resemble that of RA? How does it differ?
Similar to RA, the arthritis of MRH is inflammatory, usually chronic, symmetric, and polyarticular; it characteristically affects the interphalangeal joints of the hands and is destructive. Large joints, the feet, and occasionally C1 to C2 can also be involved. However, unlike RA, DIP synovitis and destruction may be prominent (75%), and severely deforming arthritis mutilans occurs in 50% of patients. Fever and weight loss can occur. Glucocorticoid therapy has little, if any, effect on the arthritis. Also in contrast to RA, radiographs in MRH feature well-circumscribed erosions, widened joint spaces, and absent or disproportionately mild periarticular osteopenia for the degree of erosive change. Serologies are negative, and 50% have a moderately elevated ESR. Synovial fluid can range from mildly to significantly inflammatory.
Cutaneous manifestations of MRH
Firm papulonodules, reddish-brown or yellow, occur most commonly on the face, hands, ears, arms, scalp, neck, and chest. A classic finding is “coral beads” around the nailbeds. These nodules may wax and wane and even disappear completely. They can be induced by sun exposure and may be pruritic. The nodules may coalesce on the face leading to a “leonine facies.” Lesions are less common on the legs.
What are the disorders have been associated with MRH
- • Tuberculin skin test positivity is seen in 12% to 50% of patients, but only two patients have been reported to have active tuberculosis.
- • Xanthelasma occurs in one-third of patients. Up to 60% have hyperlipidemia.
- • Malignant disease of various types has been reported in approximately 15%–30% of patients. Breast, heme, and gastric malignancies are most common. The cancer may precede, be concurrent with, or follow the development of MRH. Treatment of the malignancy can lead to improvement of the MRH.
- • Autoimmune diseases occur in 5% to 20% of patients. Multiple different autoimmune diseases have been reported.
What are the typical histologic findings of MRH on biopsy of skin or synovium?
The characteristic finding are aggregates of multinucleated giant cells and histiocytes (i.e., tissue macrophages) having a granular, ground-glass appearance. This ground-glass cytoplasm contains a periodic acid–Schiff-reactive material thought to be attributable to a mucoprotein or glycoprotein. This cellular tissue reaction has prompted the idea that MRH represents a histiocytic granulomatous reaction to an unidentified stimulus. Fat stains, such as Sudan black, are also positive. Cell markers indicate a monocyte/macrophage lineage of the histiocytes and multinucleated giant cells. Some have osteoclast markers.
How is MRH treated?
No treatment has consistently shown benefit. In patients with mild disease, symptomatic therapy with NSAIDs or nonnarcotic analgesics should be tried. Unfortunately, the arthritis in 40% to 50% of patients progresses to an arthritis mutilans. Methotrexate and antitumor necrosis factor (anti-TNF) agents have been effective for severe cases. Cyclophosphamide has also been reported to achieve partial and complete remissions. As a result of some of the cells exhibiting osteoclastic markers, intravenous (IV) bisphosphonates have shown efficacy in some patients. Most cases of MRH will resolve within 10 years leaving behind joint deformities.