Case Letter

Multicentric Reticulohistiocytosis With Arthralgia and Red-Orange Papulonodules

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Practice Points

  • Multicentric reticulohistiocytosis (MRH) is an important entity to recognize given its association with underlying malignancy and irreversible destructive arthritis.
  • Diagnosis of MRH warrants extensive review of systems, age-appropriate cancer screening, and relevant systemic workup.
  • Early pharmacologic intervention should be initiated with nonsteroidal anti-inflammatory agents or immunosuppressant agents.



To the Editor:

A 50-year-old woman presented with an asymptomatic eruption on the dorsal aspect of the hands, abdomen, and face of 6 months’ duration. The eruption was associated with generalized arthralgia and fatigue. Within several weeks of onset of the cutaneous eruption, the patient developed swelling in the hands as well as worsening arthralgia. She was treated for presumed Lyme borreliosis but reported no improvement in the symptoms. She was then referred to dermatology for further management.

Physical examination revealed red-orange, edematous, monomorphic papulonodules scattered on the nasolabial folds, upper lip, and along the dorsal aspect of the hands and fingers (Figure 1). A brown rippled plaque was present on the left lower abdomen. The oral mucosa and nails were unremarkable. Laboratory studies showed elevated total cholesterol (244 mg/dL [reference range, <200 mg/dL]), low-density lipoproteins (130 mg/dL [reference range, 10–30 mg/dL]), aspartate aminotransferase (140 U/L [reference range, 10–30 U/L]), alanine aminotransferase (110 U/L [reference range, 10–40 U/L]), and total bilirubin (1.5 mg/dL [reference range, 0.3–1.2 mg/dL]). White blood cell count and C-reactive protein levels were within reference range. An antinuclear antibody titer of 1:80 with a homogenous pattern was found, and aldolase levels were elevated. Laboratory investigations for rheumatoid factor, Lyme disease, tuberculosis, hepatitis, and human immunodeficiency virus were negative. A chest radiograph was normal.

Figure 1. Red-orange, edematous, monomorphic papulonodules scattered along the dorsal aspect of the hand and fingers.

A punch biopsy from the right dorsal hand revealed a dermal proliferation of mononucleated and multinucleated epithelioid histiocytes with ample amounts of eosinophilic ground-glass cytoplasm (Figure 2). Immunohistochemistry revealed epithelioid histiocytes reactive for CD68, CD163, and factor XIIIA, and negative for S-100 and CD1a.

Figure 2. A, Punch biopsy revealed a proliferation of mononucleated and multinucleated epithelioid cells within the dermis (H&E, original magnification ×10). B, Ample amounts of eosinophilic ground-glass cytoplasm as well as some multinucleated cells with multiple haphazardly oriented nuclei also were seen (H&E, original magnification ×40).

The patient was diagnosed with multicentric reticulohistiocytosis (MRH) and was initially treated with prednisone. Treatment was later augmented with etanercept and methotrexate with improvement in both the skin and joint symptoms.

Multicentric reticulohistiocytosis is a rare, non–Langerhans cell histiocytosis with both cutaneous and systemic features. Although case reports date back to the late 1800s, the term multicentric reticulohistiocytosis was first used in 1954.1 Multicentric reticulohistiocytosis is extremely uncommon and precludes thorough investigation of its etiology and management. The condition typically presents in the fifth to sixth decades of life and occurs more frequently in women with a female to male ratio estimated at 3 to 1.2,3 Pediatric cases have been reported but are exceedingly rare.4

Multicentric reticulohistiocytosis typically presents with a severe erosive arthropathy known as arthritis mutilans. Patients display a symmetric polyarthritis that commonly involves the elbows, wrists, and proximal and distal aspects of the interphalangeal joints. Onset and progression can be rapid, and the erosive nature leads to deformities in up to 45% of patients.2,5,6 Cutaneous findings arise an average of 3 years after the development of arthritis, though one-fifth of patients will initially present with cutaneous findings followed by the development of arthritis at any time.3,6 Clinical features include flesh-colored to reddish brown or yellow papulonodules that range in size from several millimeters to 2 cm. The lesions most commonly occur on the face (eg, ears, nose, paranasal cheeks), scalp, dorsal and lateral aspects of the hands and fingers, and overlying articular regions of the extremities. Characteristic periungual lesions classically are referred to as coral beads.4,6 Patients commonly report pruritus that may precede the development of the papules and nodules. Other cutaneous manifestations include xanthelasma, nail changes, and a photodistributed erythematous maculopapular eruption that may mimic dermatomyositis.6


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