Multicentric Reticulohistiocytosis Differential Diagnoses

Updated: Oct 10, 2019
  • Author: Alisa N Femia, MD; Chief Editor: Herbert S Diamond, MD  more...
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Diagnostic Considerations

Multicentric reticulohistiocytosis (MRH) should be considered in patients with severe arthritis. Because many other forms of arthritis are treated in a similar way, however, missing the diagnosis in the early stages of MRH may not have serious consequences.

The skin manifestations of MRH occasionally resemble those of dermatomyositis (DM), including Gottron's papule, heliotrope rash, V-neck sign, and shawl sign. Additionally, MRH occasionally presents with systemic symptoms, such as fever, weakness, myalgia, dysphagia, and Raynaud's phenomenon. [43]  Skin biopsy many be necessary to differentiate MRH from DM. [54]

Skin nodules in MRH may be clinically confused with the following:

  • Rheumatoid nodules
  • Xanthomas
  • Dermatofibromas
  • Progressive nodular histiocytomas
  • Juvenile xanthogranulomas
  • Lepromatous leprosy
  • Farber disease (lipogranulomatosis)
  • Gouty tophi
  • Sarcoidosis

One case of granuloma annulare resembling the coral-bead sign in MRH has been reported. [55]  Usually, however, a combination of clinical, histologic, and radiographic findings allow MRH to be easily distinguished from the above entities.

Other forms of histiocytosis

The histiocytoses are generally classified as Langerhans cell or non-Langerhans cell histiocytoses. MRH is a non-Langerhans cell histiocytosis. Solitary nodules identical to MRH can occur. These nodules, which are not associated with systemic disease, are called reticulohistiocytomas or reticulohistiocytic granulomas.

Other non-Langerhans cell histiocytoses that primarily affect the skin are generalized eruptive histiocytoma, indeterminate cell histiocytosis, and progressive nodular histiocytoma. In addition, juvenile xanthogranuloma (which can also affect the eye) and benign cephalic histiocytosis are also non-Langerhans cell histiocytoses primarily affecting the skin, but both conditions usually occur in young children.

Fibroblastic rheumatism is a non-Langerhans cell histiocytosis with joint and skin manifestations similar to MRH. It is often confused with MRH.

Other non-Langerhans cell histiocytoses with systemic involvement include necrobiotic xanthogranuloma (associated with paraproteinemia), Rosai-Dorman disease (associated with massive lymphadenopathy), and xanthoma disseminatum (associated with diabetes insipidus), in addition to MRH.

The name MRH should not be confused with congenital self-healing reticulohistiocytosis, which is now considered a form of Langerhans cell histiocytosis (histiocytosis X). Other forms of Langerhans cell histiocytosis affecting the skin include Erdheim-Chester disease, Letterer-Siwe disease and Hand-Schüller-Christian disease. These conditions generally also have bone involvement.

True malignant histiocytosis is extremely rare; in that disease, however, the histiocytes themselves are malignant (unlike in 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.

Other forms of arthritis

As in MRH, arthritis and skin lesions may occur in the following disorders (although none of these diseases has a polyarthritis that is as rapidly destructive as that of MRH):

  • Osteoarthritis: May produce firm nodules around the fingers but rarely elsewhere

  • Rheumatoid arthritis: Includes severe involvement of the metacarpophalangeal and metatarsophalangeal joints rather than the interphalangeal joints, though the proximal interphalangeal joints can be moderately involved, and osteoporosis develops

  • Psoriatic arthritis: Multiple forms exist, but the distal interphalangeal joints are often involved

  • Reactive arthritis (Reiter syndrome): Most commonly involves the lower extremities and sacroiliac joints

  • Lupus erythematosus

  • Gout: Gouty erosions in joints are asymmetrical; they progress slowly, and articular cartilage is preserved; calcification of the tophi may be apparent

Differential Diagnoses

  • B-Cell Lymphoma

  • Dermatomyositis

  • Fibroblastic Rheumatism

  • Gout

  • Interphalangeal Joint Arthritis

  • Juvenile Idiopathic Arthritis

  • Langerhans and Non-Langerhans Cell Histiocytoses

  • Leprosy

  • Lymphoma, Cutaneous T-Cell

  • Lymphoma, Diffuse Large Cell

  • Malignant Melanoma

  • Rheumatoid Arthritis

  • Sarcoidosis

  • Spitz Nevus

  • Squamous Cell Carcinoma