Alterations in collagen and elastin

Lichen sclerosus (et atrophicus)

Lichen sclerosus may involve skin or mucosa. Follicular plugging is common, and the plugs may resemble comedones clinically. The epidermis is commonly atrophic, and the rete pattern is effaced; however, scratching may produce pseudoepitheliomatous hyperplasia, especially in vulvar lesions. Squamous cell carcinoma rarely develops in long-standing genital lesions of lichen sclerosus and must be distinguished from pseudoepitheliomatous hyperplasia. Papillary dermal edema may produce a subepidermal bulla. Vacuolar interface dermatitis and pigment incontinence are common. Epidermotropic lymphocytes may be hyperchromatic and may mimic mycosis fungoides. The differential diagnosis also includes radiation dermatitis ( Table 13.1 ) and morphea.

Chronic radiation dermatitis

There is typically hyperkeratosis and epidermal atrophy with effaced rete that may alternate with hyperplasia. Stellate cells with large nuclei are usually present (radiation fibroblasts). The eccrine glands are atrophic and the pilosebaceous structures are absent; however, the arrector pili muscle may survive. The dermal collagen is hyalinized. Radiation elastosis may resemble solar elastosis but extends into follicular fibrous tracts. The superficial blood vessels are dilated, whereas the deeper vessels have thick walls.

The severity of radiation damage varies with the total dose, its fractionation, and the depth of penetration. Acute radiodermatitis occurs within weeks of irradiation and presents as erythema and edema followed by hyperpigmentation. Although typically diagnosed clinically, there is vacuolization and sparse degenerated keratinocytes similar to a phototoxic eruption. Chronic changes arise months to years after the initial exposure. There is atrophy, fragility, telangiectasias, altered pigmentation, and alopecia. Nonmelanoma skin cancers can develop years later and may behave in an aggressive manner with increased risk of metastasis, especially with squamous cell carcinoma.

Morphea/scleroderma

Scleroderma encompasses a group of diseases. Localized cutaneous disease may present as morphea or linear scleroderma (including en coup de sabre ). In addition to cutaneous lesions, Raynaud phenomenon and variable organ involvement characterize diffuse systemic scleroderma and limited systemic scleroderma (CREST). Although the histologic features are similar, morphea is usually more inflammatory and lacks the intimal thickening and luminal obliteration of vessels seen in systemic scleroderma.

There is controversy concerning the relationship of lichen sclerosus and morphea. Some regard lichen sclerosus as a superficial expression of morphea, explaining the lichen sclerosus–like changes in the papillary dermis overlying some lesions of morphea. However, lesions of morphea with superficial pallor do not demonstrate a superficial lymphoid band, vacuolar interface dermatitis, or follicular plugging. Deep dermal sclerosis is always present.

The sclerotic process in linear scleroderma and deep morphea (morphea profunda) extends into the subcutaneous fat and possibly fascia and bone. Unlike chronic radiation dermatitis, radiation elastosis is absent and radiation fibroblasts are not identified. Elastic fibers in morphea are often brightly eosinophilic.

Other disorders with dermal sclerosis include sclerodermoid graft-versus-host disease (GvHD), porphyria cutanea tarda, vinyl chloride exposure, and reactions to bleomycin. There are conflicting data regarding the relationship with Borrelia burgdorferi infection and morphea and lichen sclerosus. A relationship has been found in some studies in Europe; however, other studies, especially those in North America, have failed to show an association.

Sclerodermoid graft-versus-host disease

Dermal sclerosis begins in the papillary dermis and may extend into the subcutaneous tissue. In the chronic phase of GvHD, an early lichenoid stage and a later sclerotic stage can be distinguished. Each stage can occur without the other. Unlike radiation dermatitis, vascular ectasia and radiation fibroblasts are not identified. Clinically, the skin often has a corrugated appearance.

Eosinophilic fasciitis (Shulman syndrome)

Eosinophilic fasciitis is a scleroderma-like disorder of the fascia that can be distinguished by the sudden onset of painful edema and progressive induration, typically involving an extremity or extremities after strenuous exercise. The condition is named for its association with peripheral eosinophilia. Eosinophils may be found in the tissue but are not required, and are typically absent. The fibrosis and hyalinization involve the fascia and deep subcutaneous septa. In many cases, the overlying adipose tissue shows no significant changes. A deep incisional biopsy to include fascia is required for diagnosis.

Scleroderma with fascial involvement may appear similar histologically, but can be distinguished clinically. Similar changes are described in eosinophilia–myalgia syndrome secondary to L-tryptophan ingestion, although there is greater dermal involvement in eosinophilia–myalgia syndrome and the late stage is characterized by dermal mucinosis.

Elastosis perforans serpiginosa

The papules of elastosis perforans serpiginosa coalesce in an arcuate or serpiginous pattern, most commonly on the neck, face, or upper extremity. Elastic tissue stains reveal increased abnormal, thickened elastic fibers in the dermis in the vicinity of the channel.

Patients on long-term penicillamine for Wilson disease may develop altered elastic fibers with overlapping features of pseudoxanthoma elasticum and elastosis perforans serpiginosa. The penicillamine-induced, altered elastic fibers have small lateral buds arranged perpendicularly to the primary elastic fiber, resembling the twigs on a bramble bush, but do not calcify.

Elastosis perforans serpiginosa–associated disorders

The mnemonic “RAP MOPED” is helpful in remembering the associated diseases.

• R othmund–Thompson syndrome

• Acrogeria

• P enicillamine

• M arfan syndrome

• O steogenesis imperfecta

• P seudoxanthoma elasticum

• E hlers–Danlos syndrome

• D own syndrome