eMedicine Specialties > Dermatology > Benign Neoplasms

Multicentric Reticulohistiocytosis

Author: Ronald P Rapini, MD, Professor and Chair, Department of Dermatology, Professor of Pathology, University of Texas Medical School, MD Anderson Cancer Center
Contributor Information and Disclosures

Updated: Mar 10, 2008

Introduction

Background

Multicentric reticulohistiocytosis (MRH) is a rare disease in which papulonodular skin lesions containing a proliferation of true histiocytes (macrophages) are associated with arthritis. The arthritis involves the interphalangeal joints and becomes severe enough to cause severe destruction of the joints (known as arthritis mutilans) in 45% of cases (see Media File 1). 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.  

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 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.

Arthritis and skin lesions may also occur in osteoarthritis, rheumatoid arthritis, psoriatic arthritis, Reiter disease, 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. Reiter disease 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. Medscape CME courses include Hematologic Malignancies and Anti-TNF-Directed Therapies in Rheumatoid Arthritis and Update on Rheumatoid Arthritis Therapies.

Pathophysiology

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.

Clinical

History

• About one half of patients initially develop polyarthritis. One fourth of patients first develop the skin papules and the nodules. Another one fourth of patients develop skin and joint manifestations at the same time.
• Skin lesions are usually asymptomatic.
• One third of patients complain of pruritus.
• Arthritis may wax and wane, but it can rapidly become severe.
• About one third of patients have constitutional symptoms, such as weakness, weight loss, and fever.

Physical

• Skin lesions are skin colored to reddish brown.
• Lesions vary from papules that are 1-2 mm in diameter to nodules that are several centimeters in diameter.
• Papules and lesions may be isolated from one another, or they may be clustered, sometimes giving a cobblestone appearance (see Media File 3).
• The Koebner phenomenon has been reported, wherein trauma to the skin gives rise to new lesions.
• Skin lesions more commonly occur on the upper half of the body, but other areas can be involved.
  • Face and hands (90%)
  • Ears (76%)
  • Forearms (55%)
  • Elbows (40%)
  • Scalp (40%)
  • Mucosal surfaces, such as the lips, the tongue, the gingiva, and the nasal septum (50%)
• Several miscellaneous nail changes have been described, but most are due to adjacent arthritis.
• About one third of patients have been reported to have xanthelasma, but whether or not this is related to MRH is unclear.
• MRH is a polyarthritis involving a wide variety of joints.
  • Hands (76%)
  • Knees (73%)
  • Shoulders (64%)
  • Wrists (64%)
  • Hips (61%)
  • Ankles (58%)
  • Elbows (58%)
  • Feet (58%)
  • Spine (52%)

Causes

Most cases of MRH are of unknown cause, but, in about 28% of cases, the disease appears to be caused by a paraneoplastic disorder related to an underlying malignancy. MRH precedes the development of cancer in 73% of cases. Whether the malignancy is truly related to MRH is debated for several reasons.

• No consistent type of neoplasm is associated with MRH. Most of the reported specific cancer types are reported less than 5 times each in the literature.
• Because MRH is rare, a reporting bias exists in the literature toward reporting those cases with underlying malignancy, especially previously unreported malignancies. Some of these associations may be a coincidence.
• The activity of the arthritis and the skin lesions of MRH may or may not be correlated with the eradication of the cancer, unlike some paraneoplastic disorders where removal of the malignancy may produce improvement in the paraneoplastic findings.
• Some patients with MRH have been extensively studied or an autopsy has been performed with no evidence of cancer.
• MRH has been reported with cancer of the breast (scirrhous, intraductal, unspecified types), cervix, colon (adenocarcinoma), stomach (adenocarcinoma), lung (bronchogenic carcinoma, mesothelioma of pleura), bronchus, larynx, ovary (medullary carcinoma, adenocarcinoma),¹ lymphoma, leukemia, sarcoma (omentum, axilla), and melanoma. MRH has also been reported with cancers of unknown primary.

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• Multicentric Reticulohistiocytosis (Rheumatology)
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