Multicentric reticulohistiocytosis.

Multicentric reticulohistiocytosis is a rare systemic granulomatous disease of an unknown cause, characterized by distinct histopathology. The skin, mucosa, synovial, bone, and internal organs may be involved. Cutaneous nodules and distinctive arthritis are the most prominent clinical features. A 55-year-old female was referred from Orthopedic Outpatient Department, with multiple, painful and tender nodules on the dorsum of her hands, forearms, elbows, back, and neck. The lesions were present predominantly around the joints with associated arthropathies. Smaller nodules were seen on the ear helices. There was no other clinically evident or investigative abnormality. A histopathological study confirmed the diagnosis of multicentric reticulohistiocytosis.

INTRODUCTION

Multicentric reticulohistiocytosis (MRH) is a rare disease in which papulonodular skin lesions containing a proliferation of true histiocytes (macrophages) are associated with severe and rapidly destructive arthritis. The disease can involve the bones, tendons, muscles, joints, and nearly any other organ (e.g., eyes, larynx, thyroid, salivary glands, bone marrow, heart, lung, kidney, liver, and gastrointestinal tract). It has been associated with an underlying internal malignancy in about one-fourth of the cases. Females are affected more than men, with the ratio of woman to man being 3: 1.

Goltz and Laymon proposed the name multicentric reticulohistiocytosis in 1954 because of the multifocal origin and systemic nature of the disease.[1] The etiology has not been fully elucidated and no consistently effective treatment has been identified. We report this case because of its rarity.

CASE REPORT

A 55-year - old female presented with severe debilitating joint pain, involving elbows, wrists, and fingers, and multiple cutaneous lesions, since six months. This was associated with swelling and deformity of the joints, recurrent episodes of high grade fever, and loss of appetite. However, the skin lesions were asymptomatic and there was no mucosal involvement. There was no history of morning stiffness in the joints or a past major medical or surgical illness. On examination, the patient was febrile and pale with restricted mobility of the metacarpophalangeal, proximal and distal interphalangeal, elbow, and shoulder joints, with flexion deformity of the bilateral distal interphalangeal joints [Figure 1]. The rest of the systemic examination was within normal limits.

Figure 1

Nodular lesions over fingers with flexion deformitites of distal interphalangeal joints

A dermatological examination revealed discrete, but grouped, firm, reddish brown, non-scaly, non-tender papules and nodules ranging from 2 mm to 2 cm over the elbows, back, and ears [Figure 2a, b]. A hemogram revealed anemia (7.2 gm%) and a raised Erythrocyte Sedimentation Rate (48mm/hour). Routine hematological investigations, lipid profile, thyroid profile, rheumatoid factor, and C reactive protein were normal.

Figure 2

(a) Reddish brown nodules over elbows. (b) Multiple skin colored papules over pinna, neck and pre-auricular lesion

The Enzyme-Linked Immunosorbent Assay (ELISA) for Human immunodeficiency virus (HIV) was non-reactive. An electrocardiogram, chest X-ray, and ultrasound of the abdomen / pelvis were unremarkable. Histopathological examination of the skin nodule revealed multiple multinucleated giant cells and the histiocytes showed eosinophilic cytoplasm with a ground glass appearance, confirming the diagnosis of multicentric reticulohistiocytosis [Figure 3].

Figure 3

Multinucleated giant cells and histiocytes with eosinophilic cytoplasm (H and E, ×40)

The patient was started on tab Prednisolone 1 mg / kg per day and simultaneously Methotrexate was started at a dose of 15 mg / week. The patient did not come for a follow-up.

DISCUSSION

Multicentric reticulohistiocytosis, also known as lipoid dermatoarthritis, has a worldwide distribution, with a female preponderance (60 – 75%). It usually begins during the fourth decade of life with isolated polyarthritis (50%), cutaneous lesions (25%) or both concurrently (25%). The polyarthritis is usually diffuse, symmetric, progressive, and destructive, with a predilection for the distal interphalangeal joint.[2] The appearance of cutaneous manifestations and joint involvement in our patient was simultaneous in the fifth decade of her life. More than 100 cases of multicentric reticulohistiocytosis have been reported in literature, since it was first described by Weber and Freudenthal.[3] Our patient had no mucosal involvement and Balcandran et al. and Mittal et al. have reported a similar absence of mucosal involvement in their case reports.[4] Cutaneous manifestations include pink, red or brown papules, and nodules ranging from one millimeter to several centimeters in diameter, occurring most frequently on the dorsal aspect of the hands and on the face.

Other sites of involvement include the arms, scalp, pinnae, and neck, which are also the sites of involvement in our patient. Papules often occur in a periungual distribution, producing a characteristic, ‘coral beads’ appearance. Mucosal involvement, which includes the tongue and buccal or nasal mucosa, occurs in roughly one-third of the cases.[56] Active disease often remits after approximately eight years, and although it is not considered a paraneoplastic syndrome, it occurs with an associated malignancy in about 20% of the cases. Other sites of involvement can include the heart, lungs, thyroid, and bone marrow. Constitutional symptoms such as fever, malaise, and weight loss have been described, as have an elevated erythrocyte sedimentation rate (ESR), anemia, and hypercholesterolemia. Our patient had raised ESR and low Hb without any serum lipid abnormality or malignancy.[7] Diagnosis is based on the histological and immunological features of the proliferating histiocytes. On histopathology, dermal infiltration of multinucleated giant cells with eosinophilic ground glass cytoplasm is characteristic. Immunohistologically they are positive for TRAP (tartrate resistant acid phospatase), CD68, lysozyme, and human alveolar macrophage-56 (HAM-56), whereas negative for S100 protein, CD1a, and factor XIIIa. Due to financial constraints, immunohistochemistry could not be conducted on our patient.[2] There is no effective treatment for MRH. Several treatment regimens have been tried with variable success. Systemic steroids, cytotoxic drugs such as cyclophosphamide, chlorambucil, methotrexate, etanercept, and infliximab have been reported to be effective. Bisphosphonates such as alendroante and zolidronate have been reported to improve both arthritis and skin lesions.[7-9] We have reported this case because of its rarity and the characteristic histopathological findings. The proliferation of histiocytes can be a paraneoplastic response and there may be significant morbidity and mortality because of joint involvement and malignancy.