Dermatologic Manifestations of Multicentric Reticulohistiocytosis 

Multicentric reticulohistiocytosis (MRH) is a rare disease in which papulonodular skin lesions containing a proliferation of true histiocytes (macrophages) are associated with arthritis.^[1] The arthritis involves the interphalangeal joints and sometimes causes severe destruction of the joints known as arthritis mutilans in 45% of cases. The disease can involve the bones, the tendons, the muscles, the joints, and nearly any other organ (eg, eyes, larynx, thyroid, salivary glands, bone marrow, heart, lung, kidney, liver, gastrointestinal tract). It has been associated with an underlying internal malignancy in about one fourth of cases, suggesting that MRH may be a paraneoplastic condition. The proliferating histiocytes in this disease are thought to be reactive and are not themselves malignant. Also see Multicentric Reticulohistiocytosis from the eMedicine Rheumatology section.

MRH has at least 10 synonyms (eg, lipoid dermatoarthritis), but multicentric reticulohistiocytosis is now clearly the preferred appellation. Goltz and Laymon proposed the name multicentric reticulohistiocytosis in 1954 to distinguish this disease from the occurrence of histologically identical solitary cutaneous nodules called reticulohistiocytomas, which are not at all associated with systemic disease.

Skin nodules, shown in the image below, may be clinically confused with rheumatoid nodules, xanthomas, dermatofibromas, progressive nodular histiocytomas, juvenile xanthogranulomas, lepromatous leprosy, Farber disease (lipogranulomatosis), gouty tophi, and sarcoidosis.

Usually, the clinical findings combined with histologic and radiographic findings allow an easy distinction. Solitary nodules identical to MRH can occur. These nodules are not associated with systemic disease and are called reticulohistiocytomas or reticulohistiocytic granulomas. The name MRH should not be confused with congenital self-healing reticulohistiocytosis, which is now considered to be a form of Langerhans cell histiocytosis (histiocytosis X). True malignant histiocytosis is extremely rare; however, in that disease, the histiocytes themselves are malignant (unlike MRH), and the condition is associated with lymphadenopathy, hepatosplenomegaly, and often a rapidly fatal course.

With modern immunomarkers, most cases of malignant histiocytosis have been shown to be lymphoma, as the proliferating cells are usually large lymphocytes. The condition can be reclassified as a lymphoproliferative process such as CD30-positive lymphoproliferative disorder or NK-lymphoma.

Arthritis and skin lesions may also occur in osteoarthritis, rheumatoid arthritis, psoriatic arthritis, reactive arthritis (also known as Reiter disease, as Reiter was a Nazi and participated in unethical human experimentation), lupus erythematosus, and gout. Osteoarthritis may produce firm nodules around the fingers but rarely elsewhere. None of these diseases has a polyarthritis that is as rapidly destructive as MRH. Patients with rheumatoid arthritis have severe involvement of the metacarpophalangeal (MCP) joints and the metatarsophalangeal joints rather than the interphalangeal joints, though the proximal interphalangeal (PIP) joints can be moderately involved, and osteoporosis develops. Psoriatic arthritis often involves the distal interphalangeal (DIP) joints. Reactive arthritis most commonly involves the lower extremities and the sacroiliac joints. Gouty erosions in joints are asymmetric. They progress slowly, and articular cartilage is preserved. Calcification of the tophi may be apparent.

The Medscape Arthritis and Rheumatoid Arthritis Resource Centers may be helpful.

The details of the etiology are unknown. The old name lipoid dermatoarthritis reflects the previous assumption that the disease might be a storage disease because some patients had hypercholesterolemia and xanthelasma, but these findings are now thought to have been an unrelated coincidence. The disease is now thought to be mainly related to a proliferation of true histiocytes (macrophages that are derived from monocytes), which have a characteristic abundant eosinophilic ground-glass cytoplasm. This proliferation may be a paraneoplastic response to an underlying malignancy in at least a fourth of cases.

Frequency

International

Worldwide, MRH is very rare. The average dermatologist, rheumatologist, or orthopedist will see at most 1-2 cases in an entire career.

Mortality/Morbidity

The disease can cause considerable morbidity, mainly related to the occurrence of severe arthritis. This arthritis can come and go, but it can be very severe in about 45% of cases. The skin lesions also have the potential for spontaneous resolution.

• MRH may become inactive after several years, often after about 8 years.
• Morbidity or mortality can occur from the underlying malignancy. Even after the disease remits, some patients are left with crippling, deformed joints or a disfigured leonine facies.

Race

MRH affects all races, but about 88% of the reported cases have been in white patients.

Sex

Like many other rheumatologic diseases, females are affected more often than men. The ratio of women to men for MRH is 3:1.

Age

MRH can be found in teenagers or in elderly persons, but it most commonly begins in early middle age, with the average age of onset at about 43 years.