Calcifying and Ossifying Disorders of the Skin

Autoimmune Connective Tissue Disease

Dystrophic calcification may be seen in any of the autoimmune connective tissue diseases (AI-CTDs), but it is most common in childhood dermatomyositis and in the CREST form of systemic sclerosis. As a comparison, cutaneous calcification develops in 10–20% of patients with adult dermatomyositis, whereas it occurs in ~50–70% of children with the disease (see Fig. 42.8 ) . The presence of dermatomyositis-associated calcinosis correlates with longer disease duration, fingertip ulceration, and anti-NXP-2 autoantibodies, while a negative correlation exists with anti-transcriptional intermediary factor 1-γ antibodies . Small deposits may occur in the skin or larger firm masses may begin in the muscle groups most severely affected by the disease. The most frequently involved sites are the elbows, knees, buttocks, and shoulders. Extrusion of calcium through the skin causes significant morbidity with pain and secondary infection.

In calcinosis universalis, the most severe form of dystrophic calcification, there is diffuse involvement with sheet-like masses of calcium. Calcification occurs along fascial planes, often leading to severe functional impairment. Aggressive treatment of dermatomyositis with immunosuppressive agents and/or IVIg may be warranted to try to limit this serious complication (see Ch. 42 ). However, once calcification has developed, the effectiveness of these therapies can be quite variable.

The CREST ( c alcification, R aynaud phenomenon, e sophageal dysmotility, s clerodactyly, and t elangiectasia) variant of systemic sclerosis is the other AI-CTD in which cutaneous calcification is frequently seen. Calcification is usually less severe than in dermatomyositis and is usually restricted to the hands and upper extremities ( Fig. 50.1 ); it is also seen over bony prominences and tendons. Extrusion of white chalky material is sometimes followed by localized ulceration, often at sites of trauma such as the digits. Calcinosis universalis can occur in systemic sclerosis, but much less frequently than in dermatomyositis.

Dystrophic calcification has occasionally been reported in chronic cutaneous, acute systemic, and subacute cutaneous lupus erythematosus as well as generalized morphea ( Fig. 50.2 ) . Calcification may also occur within lesions of lupus panniculitis. In systemic lupus erythematosus, calcification is most often an asymptomatic radiologic finding.

Panniculitis

Any lobular panniculitis may develop focal dystrophic calcification, including pancreatic panniculitis, lupus profundus, and subcutaneous fat necrosis of the newborn (see Ch. 100 ). In the latter, the calcium deposits are small and are most easily noted radiologically; occasionally, more widespread deposits may be seen .

Genetic Disorders

A number of genetic disorders may be accompanied by cutaneous calcification, including pseudoxanthoma elasticum (PXE; see Ch. 97 ). The coexistence of typical elastic fiber calcification along with small discrete foci of cutaneous calcification or ossification has been reported . PXE results from inactivating mutations in ABCC6 which encodes a membrane transporter system . ABCC6 directly mediates the sinusoidal release of ATP from the liver, which is then converted to AMP and inorganic pyrophosphate (PPi) within the liver vasculature . PPi normally prevents the matrix calcification that is thought to create the findings in PXE . In addition, serum levels of fetuin-A, another major anti-mineralization protein, are significantly reduced in PXE patients . These factors, combined with impaired carboxylation of the inhibitor matrix Gla protein, may allow for increased responsiveness to pro-calcifying stimuli and unchecked calcification of elastic fibers in affected tissues .

Ehlers–Danlos syndrome encompasses multiple disorders in which genetic mutations lead to abnormal collagen synthesis, metabolism, or function (see Ch. 95 ). Patients develop hard subcutaneous nodules known as spheroids or spherules over bony prominences, which are thought to represent herniated fat lobules that have become calcified (see Ch. 97 ). It is also possible that minor trauma results in scar tissue which then becomes a focus for dystrophic calcification . Of note, similar calcifications can occur within the breast in these patients and their detection by mammography may lead to false-positive radiographic findings for breast carcinoma.

Dystrophic calcification may also be seen in patients with porphyria cutanea tarda (PCT; see Ch. 49 ). It occurs most often in patients with longstanding disease who develop sclerodermoid changes and secondary calcification within these areas . As with the other lesions of PCT, calcification appears most often in the head and neck region or on the dorsal surface of the hands. Ulceration has also been reported, although rarely, in association with these lesions.

Other rare genetic syndromes in which cutaneous calcification may be seen include Werner syndrome and Rothmund–Thomson syndrome (see Ch. 63 ). Cerebral amyloid angiopathy , an autosomal dominant condition due to mutations in the gene encoding the amyloid precursor protein, can present with dementia, patchy leukoencephalopathy, hemorrhagic stroke, external carotid artery dysplasia, and occipital calcifications . Microcalcification of the dermal blood vessels may also be seen, and while the latter is asymptomatic, dermatologists might be called upon to biopsy the skin as a diagnostic measure.

Infections

Infections, particularly parasitic, can lead to dystrophic calcification. Calcified cysts form around larvae or worms, including Onchocerca volvulus and the tapeworm Taenia solium . Intrauterine herpes simplex viral infections may cause annular plaques of calcinosis cutis in newborns.