Tammie Ferringer

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 commonly 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 (Table 13.1). The differential diagnosis also includes radiation dermatitis 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. Non-melanoma skin cancers can develop years later and may behave in an aggressive manner with increased risk of metastasis, especially in 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’s 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 never 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 (GvHD) disease, 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 resulted in negative findings.

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’s 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 following 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’s 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.

Reactive perforating collagenosis

The primary lesion is a small papule with a hyperkeratotic central umbilication. Classic, true reactive perforating collagenosis is an inherited genodermatosis, most often in an autosomal-dominant pattern. These lesions occur in children and are precipitated by minor trauma.

An adult, acquired form has been described in association with diabetes and chronic renal failure. This form, known as acquired perforating dermatosis or perforating disorder of renal disease, encompasses features of Kyrle’s disease and perforating folliculitis.

Scar and keloid

Acne keloidalis nuchae

The plasma cell infiltrate is related to the predominance on the posterior neck. Plasma cells are typically a component of the inflammatory infiltrate on the face, occipital scalp/posterior neck, axillae, breast, genital area, and shins. Hair shafts free in the dermis are surrounded by microabscesses and/or giant cells.

Favre–Racouchot syndrome (nodular elastosis with cysts and comedones)

This solar degeneration condition presents with yellowish plaques lateral to the eyes that are studded with cysts and multiple open comedones. Smoking may act in conjunction with the solar damage to create this syndrome. Solar elastosis is a bluish, amorphous material that is primarily sun-damaged elastic and/or collagen fibers.

Chondrodermatitis nodularis helicis

Depending on the depth of the biopsy, cartilage may be present but is not required for diagnosis. Collagen degeneration occurs from a combination of pressure, poor vascularity, and solar damage (see Chapter 15).

Acrodermatitis chronica atrophicans

Borrelial spirochetes may be found with silver stains. This is a late manifestation of infection by Borrelia. It is most frequently reported in Europe, where B. afzelii is endemic.

Ochronosis

The inherited form, also known as alkaptonuria, is an autosomal-recessive disorder due to homogentisic acid oxidase deficiency. Exogenous ochronosis occurs as a result of application of hydroquinone or contact with phenol (carbolic acid).

Colloid milium

The adult type develops in the setting of severe sun damage, on the face, neck, and dorsal hands. This material represents the final product of severe solar degeneration but can stain weakly with amyloid stains (crystal violet, Congo red, thioflavin T). However, it fails to react with pagoda red. The juvenile form develops on the head and neck before the development of sun damage. This type is Congo red-negative but positive with antikeratin antibodies confirming the origin of the material from degenerated keratinocytes.

Anetoderma

These oval lesions have an atrophic or wrinkled surface and bulge outward or are slightly depressed and herniate inward with pressure. The upper trunk and upper arms of young adults are typically affected. Primary lesions have been reported with (Jadassohn–Pellizzari type) and without (Schweninger–Buzzi type) a preceding inflammatory stage. Clinically inflamed lesions may have a perivascular and sometimes interstitial infiltrate but established lesions look like normal skin on H&E-stained sections and reveal minimal to no elastic fibers with special stains. Secondary anetoderma can occur from various processes including syphilis, other infectious processes, granulomatous diseases, lupus, and lymphoma.

Atrophoderma

Lesions typically are sharply demarcated gray-brown, atrophic, round to oval, depressed areas with a “cliff-drop” border. Some have suggested that atrophoderma is an atrophic abortive variant of morphea. In contrast to morphea, there is no violaceous border or induration, and lesions tend to be chronic. A superficial perivascular and interstitial inflammatory infiltrate consisting of lymphocytes and histiocytes can be seen. Elastic fibers appear normal.

Connective tissue nevus

Connective tissue nevi are hamartomas of the extracellular connective tissue, whether it is collagen, elastic, or glycosaminoglycans, that is present in abnormal amounts. Collagenomas can be inherited in an autosomal dominant pattern or associated with Proteus syndrome and tuberous sclerosis (shagreen patches). They present as skin-colored papules, nodules or plaques. Elastomas are associated with Buschke–Ollendorff syndrome.

Aplasia cutis congenita

Aplasia cutis is due to congenital absence of skin. It may present as an ulceration, membranous lesion, or atrophic scarring, most commonly on the vertex of the scalp. It may be associated with limb defects (Adams–Oliver syndrome), mental retardation, epidermal nevi, epidermolysis bullosa (Bart syndrome), chromosomal abnormalities, fetus papyraceus, or focal dermal hypoplasia.

Further reading