MUCINOSES BY Dr. Saad Raheem Abed

Mucinoses Mucins are jelly-like acid glycosaminoglycans (formerly known as mucopolysaccharides) of the ground substances and probably play a part in the extravascular exchange of metabolites. Mucin is normally produced in small quantities by fibroblasts. Acid glycosaminoglycans, such as hyaluronic acid and heparin, stain with toluidine blue, colloidal iron, or with alcian blue at pH 2.5, the coloration depending on the number and nature of the acid groups. PAS stains heparin, but not hyaluronic acid. In general, acid glycosaminoglycans stain much brighter in frozen fixed tissue, or in 1% cetylpyridinium chloride solution, rather than in formalin-fixed biopsies.

Classification of the cutaneous mucinoses  Primary  Diffuse (degenerative-inflammatory mucinoses)  Generalized myxoedema  Pretibial myxoedema  Lichen myxoedematosus (papular mucinosis, scleromyxoedema)  Reticular erythematous mucinosis (plaque-like mucinosis)  Scleroedema  Self-healing juvenile cutaneous mucinosis  Cutaneous mucinosis of infancy  Papular and nodular mucinosis associated with lupus erythematosus  Papular mucinosis of the toxic oil syndrome

Primary  Focal (neoplastic-hamartomatous mucinoses): -Cutaneous focal mucinosis -Mucous (myxoid) cyst -Acral persistent papular mucinosis -Mucinous naevus  Follicular forms: -Follicular mucinosis (alopecia mucinosa) -Urticaria-like follicular mucinosis

Secondary -Collagen vascular diseases (especially dermatomyositis, lupus erythematosus) -Malignant atrophic papulosis (Degos’ syndrome) -Hereditary progressive mucinous histiocytosis -Papular mucinosis in L-tryptophan-induced eosinophilia– myalgia syndrome -Mucinosis accompanying mesenchymal and neural tumours

Lichen myxoedematosus syn. papular mucinosis; lichen fibromucinodosis; scleromyxoedema Lichen myxoedematosus is a cutaneous myxoedematous state characterized by the formation of numerous lichenoid papules which coalesce together to form generalized plaques, causing extensive thickening and hardening of the skin. It is a rare disorder characterized by proliferation of fibroblasts with fibrosis and excessive deposition of acid glycosaminoglycans in the skin, and is distinct from scleroderma. Montgomery and Underwood divided it into four types:  1 a generalized lichenoid papular eruption (scleromyxoedema);  2 a discrete papular form;  3 a localized to generalized lichenoid plaque form; and  4 an urticarial plaque form.

A recent review of this area suggests that there are really only two main divisions of lichen myxoedematosus, a generalized papular and sclerodermoid form (scleromyxoedema) and a localized papular form. Scleromyxoedema is usually associated with a monoclonal gammopathy. Serum from patients with lichen myxoedematosus, even after elution of the IgG paraprotein, can stimulate synthesis of DNA and cell proliferation in cultured fibroblasts. Localized forms of lichen myxoedematosus, without ademonstrable paraprotein, are recognized, and include a discrete papular form involving any site.

acral persistent papular mucinosis involving only the extensor surface of the hands and wrists.

PHYSICAL FINDINGS: Scleromyxedema  In scleromyxoedema (the Arndt–Gottron syndrome) the pattern of lichen myxoedematosus is confluent, papular and sclerotic. Flesh colored to yellow/red, papular skin eruption, Indurated with a cobblestone feel  Distribution includes head, posterior auricular area, neck, arms and trunk  Midportion of back can be involved  NOT involved in scleroderma  Sclerodactyly can be present on the hand, simulate the sclerodactyly of scleroderma, but the clinical appearance of numerous small papules of more or less uniform size, often in linear patterns on an erythematous and palpably thickened background, is very distinctive.

Fig. Lichen myxoedematosus. Close up of micropapules behind earlobe. Fig. Scleromyxoedema. View of forehead showing sclerodermoid appearance and linear papulation.

Fig.Scleromyxoedema. Sclerodermoid appearance of finger.

Fig.Scleromyxoedema. Sclerodermoid appearance of face

Fig.Scleromyxoedema. Sclerodermoid appearance of neck and chest.

Histopathology Mucinous deposits occur in the middle and deeper layers of the dermis, where they displace collagen fibres, but do not involve the dermal papillae or accumulate around blood vessels. Histochemically,the mucinous deposits are heterogenous mixtures of acid glycosaminoglycans, which stain positively with alcian blue and toluidine blue. Large, stellate, elongated fibroblasts are present within the mucinous stroma. Mucin deposition in the media and adventitia of vessels and in many organs including the myocardium is reported, and the skeletal muscles may be infiltrated with lymphocytes

Diagnosis. Infiltrates appearing in and around old scars may simulate ‘scar sarcoidosis’. Papules on the dorsa of the hands and ears may cause confusion with granuloma annulare. Systemic scleroderma may show many features simulating scleromyxoedema. However, in scleroderma the skin is thickened and bound-down, whereas in scleromyxoedema it is also thickened but moveable over the subcutis. Papules are absent in scleroedema and scleroderma, but common in scleromyxoedema.

Prognosis. The prognosis of scleromyxoedema is poor despite the introduction of treatment with cyclophosphamide and melphalan. Death may result from non-specific complications such as bronchopneumonia, coronary occlusion or from haematological malignancies

LABORATORY DATA: Scleromyxedema  Monoclonal gammopathy with lambda chains  Level of paraprotein does not decrease after effective treatment  Pathogenesis unclear  Mucinous deposition throughout the dermis  Thick collagen bundles  Increased fibroblast-like cells  Inflammatory infiltrate  Autoimmune markers typically negative

TREATMENT: Scleromyxedema  Variable immunosuppressants have been tried  IVIG 2g/kg monthly for 2-3 months then maintenance every weeks  Melphalan  Cyclophosphamide  Cyclosporine  Thalidomide  Stem cell transplant has been used