MULTICENTRIC

RETICULOHISTIOCYTOSIS

 

Clinical Findings

CUTANEOUS LESIONS

MRH is characterized by the association of a cutaneous and mucosal eruption with severe arthropathy and other visceral symptoms. The papulonodular lesions range in diameter from a few millimeters to 2 cm and are round, translucent, and yellowrose or yellow-brown . Grouping of lesions into plaques can give a cobblestone appearance, but lesions are generally scattered and isolated . They do not tend to ulcerate and are pruritic in about one-third of cases. These lesions preferentially affect the fingers , the palms and backs of the hands, the juxta-articular regions of the limbs, and the head . Small scattered lesions may be found on the trunk. Periungual papules , arranged around the nail folds, resemble “coral beads” and have been noted in approximately 40 percent of cases. Severe involvement of the face may lead to a leonine facies. Xanthomatous lesions are found in 30 percent of cases. Periarticular nodules, resembling rheumatoid nodules, may occasionally be seen. Erythematous, photodistributed macules and papules have been observed in approximately 15 percent of cases and may be confused with dermatomyositis. Nail changes, including brittleness, longitudinal ridging, and atrophy, may occur. Almost 50 percent of affected patients have specific nodular lesions of the oral, nasal, and pharyngeal mucosae.

 

Differential Diagnosis of Xanthoma Disseminatum

Most Likely

·         Chronic disseminated Langerhans cell histiocytosis

·         Tuberous xanthoma (hyperlipemic)

·         Papular xanthoma

Consider

·         Juvenile xanthogranuloma

·         Generalized eruptive histiocytosis

·         Multicentric cutaneous reticulohistiocytosis

·         Progressive nodular histiocytosis

Two different sub-types without joint or visceral manifestations have been described: solitary cutaneous reticulohistiocytosis (or reticulohistiocytoma cutis) and diffuse cutaneous reticulohistiocytosis. Solitary cutaneous reticulohistiocytosis is characterized by a single firm, rapidly growing nodule varying in color from yellow-brown to dark red . Its most common location is the head, but it may be found in almost any cutaneous site. It occurs without evidence of systemic involvement, and its onset may be preceded by trauma.

Diffuse cutaneous reticulohistiocytosis is a purely cutaneous form characterized by the eruption of firm, smooth, asymptomatic papulonodular lesions, 3 to 10 mm in diameter, scattered diffusely over the skin. The color of early lesions is pinkish yellow, whereas older lesions show a red-brown color.

 

RELATED PHYSICAL FINDINGS

In MRH, severe chronic diffuse polyarthritis with arthralgias is the initial sign of the disease in up to two-thirds of cases. The lesions symmetrically involve the hands (80 percent of cases), knees (70 percent), wrists (65 percent), and less frequently the shoulders, ankles, elbows, hips, feet, and spine. The osteoarticular lesions show a progressive destructive course for 6 to 8 years and then become stable. Involvement of the muscles (myositis, myotonia, and myoatrophy), cardiopul-monary system (pericarditis, cardiac insufficiency, pleuritis, pulmonary infiltration), eyes (exophthalmos, conjunctival infiltration), gastrointestinal system (gastric ulcer), thyroid gland (thyroid nodules), and submandibular salivary glands have occasionally been reported, but histologic documentation of involvement at these sites is rare. Fever, weight loss, and weakness can be present. The term familial histiocytic dermatoarthritis is used to indicate a particular form of MRH characterized by familial occurrence and typical ocular involvement (glaucoma, uveitis, and cataracts). Internal malignancy may be associated in 15 percent to 27 percent of cases. Solid tumors such as bronchial, breast, gastric, and cervical carcinomas are most common. Lymphomas and myelodysplastic syndromes have been found less frequently, and malignant melanoma has been reported in three cases. Whether MRH can be interpreted as a true paraneoplastic disease is not clear. Whatever the nature of the association, the incidence of internal neoplasia is such that patients who come for treatment of MRH should be investigated for concomitant internal neoplasm. MRH has been described in association with autoimmune diseases, systemic vasculitis, tuberous sclerosis, sclerosing lesions of the leg, and tuberculosis.

Laboratory Tests

In MRH, elevated erythrocyte sedimentation rate and anemia have been observed in about half of patients and hypercholesterolemia in one-third of cases. An increase in immunoglobulin G and the presence of cryoglobulinemia and cold agglutinins have occasionally been reported. Rheumatoid factor is usually not detected. Radiographically, the joint lesions of MRH are characterized by bilateral, symmetrical, sharply circumscribed, and rapidly progressive erosions that spread from the margins to the joint surfaces, often with concomitant separation of the bone ends but without subchondral sclerosis.

Histopathology and Ultramicroscopic Findings

The histologic findings in MRH and its sub-types are identical. Histologically, the early lesions may be composed of histiocytes and lymphocytes, and therefore may be confused with other cutaneous histiocytoses. Older lesions show the presence of numerous large, mononucleated or multinucleated histiocytes with an abundance of eosinophilic, homogeneous cytoplasm containing fine granules that has a ground-glass appearance (Fig. 149-13). The number of giant cells may vary, and the diameter of these cells may reach 100 nm. The nuclei of the multinucleated cells may be arranged haphazardly or they may align along the periphery or cluster in the center. Plasma cells and eosinophils are sometimes present. Fragmentation and clumping of collagen and elastic fibers have been reported. At times, connective tissue and cell phagocytosis may be seen. Histochemically, the granular material in histiocytes and giant cells stains with periodic acid-Schiff after diastase digestion, Sudan black, and scarlet red, which indicates

the presence of glycolipids and/or glycoproteins and neutral fat.

 

Complications

Complications occurring in MRH are mainly due to visceral involvement of the disease. Lesions in the upper airway may lead to dysphonia and/or dysphagia. Cardiopul-monary manifestations are more frequently reported and may also be fatal. In addition, bones and all the visceral organs may be affected, which leads to weight loss and pyrexia that complicate the potentially mutilating inflammatory polyarthritis.

Prognosis and Clinical Course

The purely cutaneous forms of reticulohistiocytosis may involute spontaneously. It is possible that the diffuse, purely cutaneous form is an early stage of MRH before the appearance of joint and visceral lesions. In MRH, the mucocutaneous course does not parallel the articular course. The mucocutaneous lesions have an unpredictable course and may remit spontaneously. In half of the patients, the osteoarticular manifestations become stable, whereas in the other half, they cause progressive destruction. The prognosis is favorable for cutaneous forms. The prognosis for MRH is related to the severity of the osteoarticular manifestations, the presence of visceral involvement, and underlying neoplasms if present.

 

Differential Diagnosis of Multicentric Reticulohistiocytosis

Most Likely

·         Rheumatoid arthritis

·         Dermochondrocorneal dystrophy

·         Familial histiocytic dermatoarthrosis

·         Lipodermoarthrosis

·         Progressive nodular histiocytosis

Consider

·         Farber lipogranulomatosis

·         Xanthoma disseminatum

·         Lipoid proteinosis

·         Lepromatous leprosy

·         Sarcoidosis

·         Self-healing cutaneous mucinosis

·         Fibroblastic rheumatism