The pathogenesis of RH and MRH is largely unknown. These disorders most likely represent nonneoplastic histiocytic reactions occurring secondary to an underlying inflammatory process,¹ such as malignancy or autoimmune disease in the case of MRH.² Regardless of stimulus, the localized histiocytic proliferation likely results from macrophage activation by cytokines and inflammatory mediators including certain interleukins and TNFα.³ In MRH, the same cytokines are hypothesized to also result in the systemic symptoms such as arthritis.³ Infectious or neoplastic etiologies for RH have also been postulated but not proven,^1,3 and given the known associations between systemic inflammatory disease and MRH, seem less likely.

Given the rarity of RH and MRH, their incidence is unknown. The mean age of onset of MRH is 43 to 53 years.^4,5,6,7,8 Occasionally, MRH presents in childhood.^7,9 There is a female preponderance with a male:female ratio of approximately 1:3.^4,5,6,7 MRH may occur more frequently in Caucasians than in other groups,⁴ but most series of MRH originate from the United Kingdom or the United States and Caucasians may be overrepresented.

The median age of presentation of solitary RH is approximately 35 years, with a male:female ratio of approximately1.4:1.¹ The occurrence of multiple cutaneous RHs in patients without systemic features of MRH such as arthropathy is extremely rare. In a review of 10 such cases, the median age was 59 years (range 8 to 68), with a male:female ratio of 3:7.¹⁰

The initial manifestation of MRH is polyarthritis in approximately two-thirds of patients, which is followed by a cutaneous eruption months to years later.⁴ Approximately 20% of cases will initially present with cutaneous disease, and a similar proportion present with simultaneous skin and joint disease.^4,5 Mucosal membranes are involved in half of cases, with the oral and nasal mucosa most frequently involved, and mucosal disease usually occurs concurrently with skin involvement.^4,5 Cutaneous involvement consists of red to yellow-brown, often pruritic, papules and nodules ranging in size from 1 mm to several centimeters.^4,6 The skin of the face and dorsal hands is most frequently involved, with over 90% of cases demonstrating the characteristic nodules at these sites.^4,5 Facial disease can be extensive and disfiguring. Involvement of the ears or scalp occurs in the majority of cases.⁴ Periungual nodularity is characteristic, resulting in the classical “coral band” appearance,⁴ and lesions at mucocutaneous junctions such as the corner of the mouth and nasal alae are common.⁶ Less frequently involved sites include the chest, back, abdomen, and extremities. In a minority of patients, the nodularity may be preceded by an erythematous rash resembling dermatomyositis.^5,11 Overlying ulceration of the nodules is infrequent.⁴ Mucosal nodules are similar in gross appearance to cutaneous nodules.

Joint involvement of MRH is polyarticular, typically symmetric, rapidly progressive, and involves the distal and proximal interphalangeal joints in the vast majority of patients.^4,6 Metacarpophalangeal involvement is also fairly common, and involvement of large joints including the shoulders, elbow, knees, and ankles is seen in most patients; spinal involvement occurs in about half of patients.^4,6 Involvement of the interphalangeal joints is most severe, often eventually progressing to an erosive arthropathy with destruction of articular cartilage and bone, shortening of fingers, and deformation of the hands. There is often waxing and waning of disease activity including arthritis and associated skin lesions.⁴ Rare case reports of MRH have described involvement of sites other than the skin and joints, including liver, lungs, thyroid, salivary glands, and bone marrow, among others.^12,13 Systemic symptoms including weight loss, weakness, malaise, and fever are seen in a subset of patients.^4,8 Reported abnormalities in laboratory values include an elevated erythrocyte sedimentation rate in half of patients, and anemia and hyperlipidemia less frequently.^4,5,8 Patients with MRH may have an increased incidence of xanthelasma.⁴ Radiographs demonstrate articular erosion and resorption of articular bone in the majority of patients.^4,6