Erythematous, pruritic leg plaques - Clinical Advisor

Erythematous, pruritic leg plaques

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  • Case 1_1112 Derm Look 1

  • Case 2_1112 Derm Look

Case #1

A 75-year-old woman with a history of hypothyroidism presented with extremely itchy red plaques on her trunk and extremities. The eruption started on her shins and generalized. She had been treated previously with both oral and topical antifungals for presumed tinea corporis, but the eruption had worsened and began blistering. A skin biopsy demonstrated a subepidermal blister with eosinophils. Fluorescent stains for complement and immunoglobulin (Ig) G showed a linear staining pattern along the dermal-epidermal junction.


Case #2

A man, aged 65 years, presents with itchy red patches on his trunk and extremities. He was previously diagnosed with “dermatitis” and had been using a topical corticosteroid for the past two weeks. The ointment relieved some of the itchy sensation, but the the rash had not resolved. History was significant for poorly controlled type 2 diabetes. Physical exam showed large pink plaques with inflamed borders. Toenails were thickened and yellow with subungual debris. A skin scraping from the border of the leg lesion demonstrated hyphael elements.




HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Itchy leg bullae after a trip outdoors and Firm, red plaques and xerotic skin.

Case #1: Bullous pemphigoidBullous pemphigoid (BP) is an autoimmune blistering disease in which circulating autoantibodies bind to the proteins in the skin that attach the dermis to the epidermis. The autoantibody implicated in BP is against a protein called BP180,...

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Case #1: Bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering disease in which circulating autoantibodies bind to the proteins in the skin that attach the dermis to the epidermis. The autoantibody implicated in BP is against a protein called BP180, which is a component of the hemidesmosome.

Hemidesmosomes are responsible for attaching the basal keratinocytes of the epidermis to the dermis. Patients may also have autoantibodies against a second protein called BP230, but BP180 is considered to be the pathogenic antibody in this disease. When the autoantibodies bind to their targets in the skin, an inflammatory reaction ensues; this accounts for the clinical manifestations of the disease.1,2

Rarely present in children, BP is generally a disease of the elderly and typically presents after age 60 years. The risk of developing BP increases with age. Someone aged 90 years has a 300-fold greater risk of developing BP than does an individual younger than age 60 years. Men may be at greater risk than women.1.2

There is a broad spectrum of clinical presentations. The classic presentation is a pruritic eruption with the development of tense blisters. Prior to the onset of blisters, patients may suffer for weeks to months with the prodromal nonbullous phase of the disease, which may be quite variable.

Manifestations of the nonbullous phase include pruritis without rash, eczematous plaques, or excoriated urticarial lesions. A percentage of patients will never progress to the bullous phase of the disease.

In the bullous phase of BP, vesicles and bullae develop on normal-appearing skin or are associated with urticarial or eczematous plaques. The vesicles and bullae may rupture, leaving crusted erosions.

The characteristic distribution includes the trunk, thighs, groin, axilla and volar forearms. The shins frequently serve as the initial site of the eruption. The oral mucosa is involved in 20% of cases. Other mucous membranes are rarely involved. A peripheral blood eosinophilia is present in 50% of patients.1,2

BP has are several clinical variants. Vesicular pemphigoid features small, tense, grouped vesicles. In pemphigoid nodularis—a variant that may resemble prurigo nodularis—pruritic papules and nodules occur on the scalp and extremities. In erythrodermic pemphigoid, patients present with erythroderma.

Rarely, BP may occur in association with lichen planus in a variant termed lichen planus pemphigoides. BP localized to the palms and soles may resemble dyshidrotic eczema but is called dyshidrosiform pemphigoid. In vulvar childhood pemphigoid, young girls present with lesions limited to the vulva.

In gestational pemphigoid, women present in the second or third trimester of pregnancy with urticarial plaques that subsequently develop vesicles and bullae. Most commonly, the lesions in gestational pemphigoid involve the abdominal region, including the umbilicus.

This contrasts with pruritic urticarial papules and plaques of pregnancy, another pregnancy dermatosis that characteristically spares the umbilicus. All variants of BP share common histologic features and are attributable to autoantibodies to BP180.1,2

BP generally is not believed to be a paraneoplastic syndrome; however, there are rare instances in which BP is clearly associated with the onset of a malignancy. Additionally, other autoimmune diseases (e.g., autoimmune thyroid diseases and collagen vascular diseases) are not clearly associated with BP.

Occasionally, systemic medications are implicated in the development of BP. These medications include furosemide (Delone, Furocot, Lasix, Lo-Aqua), penicillamine (Cuprimine, Depen) and captopril (Capoten), among others.1,2

Because of the polymorphic presentation of BP, establishing the diagnosis requires a high degree of clinical suspicion. Typically, establishing the diagnosis involves two punch biopsies.

One biopsy is taken from an obviously diseased skin area, such as a blister or urticarial plaque. This specimen will be sent for routine hemotoxylin and eosin staining. If a frank blister is present, the blister will be in a subepidermal location, and the blister cavity will have eosinophils and occasionally neutrophils. If the biopsy is taken from an urticarial or nonbullous area, then the findings are less specific and may include subepidermal clefting and eosinophilic spongiosis.

The second biopsy is taken from perilesional skin (normal-appearing skin immediately adjacent to clinically involved skin). This specimen will be sent for direct immunofluorescent (DIF) microscopy. In DIF microscopy, the specimen is processed with a fluorescent stain for complement (C3) and various immunoglobulins (IgG, IgM, and IgA).

In BP, the DIF microscopy demonstrates linear deposits of C3 and IgG along the epidermal basement membrane. When the diagnosis is in doubt, the specimen can be split at the dermal-epidermal junction. In BP, the fluorescent staining will appear on the epidermal side of the split. This contrasts with such other subepidermal autoimmune blistering diseases as epidermolysis bullosa acquisita, in which the stain appears on the dermal side of the split. Another way to establish the diagnosis is through testing of the patient’s serum for the circulating autoantibodies against BP180 or BP230. There is now a commercially available enzyme-linked immunosorbent assay (ELISA) to assess for these autoantibodies.1,2

The differential for BP includes drug reactions, contact dermatitis, prurigo, and urticarial eruptions. BP can be distinguished from these dermatoses by the characteristic findings on immunofluorescence and histopathology. Additionally, ELISA may be useful in supporting the diagnosis of BP.1,2

There are few controlled clinical studies pertaining to the treatment of BP. Treatment guidelines are based on clinical experience and consensus opinion. Oral prednisone at a dose of 0.5-1.0 mg/kg/day will typically control the disease within weeks.

The prednisone is subsequently tapered over a period of months. It is important to monitor (and provide prophylaxis when applicable) for such side effects of long-term oral corticosteroid therapy as osteoporosis, hypertension, infection, and cataracts. Potent topical corticosteroids may be as effective as oral corticosteroids with fewer side effects. Additional treatments include such other oral immunosuppressive medications as azathioprine (Azasan, Imuran), methotrexate (Rheumatrex, Trexall), cyclosporine (Gengraf, Neoral, Sandimmune, Sangcya), mycophenolate mofetil (Cellcept), cyclophosphamide (Cytoxan), and chlorambucil (Leukeran). Novel therapies include the combination of niacinamide and tetracycline.1,2

The patient in this case was treated with oral prednisone at an initial dose of 60 mg daily. Within four weeks, her skin was clear. The steroids were tapered over the next four weeks. Her skin has remained clear for six months.

Case #2: Tinea corporis

The term tinea indicates an infection of the most superficial layer of the skin (stratum corneum) caused by species of fungus known as dermatophytes. The commom term for tinea is ringworm.

Dermatophyte infections of the hands are termed tinea mannum; tinea pedis refers to the feet; tinea cruris refers to the groin; tinea facei refers to the face; tinea capitis refers to the scalp; and tinea unguinum refers to the nails.

The patient in this case was diagnosed with tinea corporis, a dermatophyte infection of the trunk and extremities. Tinea corporis most commonly presents as round, sharply demarcated patches that sometimes have central clearing and frequently feature an inflammatory or active border with scale and pustules.

Patients may complain of itching or burning. In the setting of topical-corticosteroid use, the scale and pustules are absent or subtle and the patient may be entirely asymptomatic, a condition referred to as tinea incognito. Although topical corticosteroids may mask the scale, pustules, and pruritus, they ultimately lead to an exacerbation of the infection.3,4

The most common cause of tinea corporis is Trychophyton rubrum, followed by T. mentagrophytes. Tinea corporis can be spread from human to human, from soil to human, or from animal to human. Patients at risk for tinea corporis may have a personal history of (or a close contact with) tinea capitis, tinea pedis, or tinea unguinum.

Other risk factors include close contact with domestic animals, immunosuppression, and recreational or occupational exposures to such facilities or activities as locker rooms, military housing, and wrestling. Immunosuppression does not lead to an increased incidence of tinea infections, but it will lead to increased severity and greater risk of recurrence of such an infection.3,4

Variants of tinea corporis include Majocchi’s granuloma, tinea profunda, and tinea imbricata. Majocchi’s granuloma is caused by T. rubrum and presents as perifollicular pustules. This condition is frequently seen in people with tinea pedis or onychomycosis who shave their legs and subsequently develop an infection of the hair follicles.

Tinea profunda results when an individual develops an excessive inflammatory respose to the dermatophyte infection. Tinea profunda may appear verrucous or granulomatous, mimicking a deep fungal infection, squamous cell carcinoma, or cutaneous mycobacterial infection.

Found only in equatorial regions, tinea imbricata is caused by T. concentricum and appears as concentric annular rings that have the appearance of wood grain.

The diagnosis of tinea corporis frequently can be made clinically by the classic appearance of annular patches with an inflammatory border. When the diagnosis is in doubt, a skin scraping will demonstrate fungal elements when examined under the microscope.

Skin biopsies are occasionally required. In the skin biopsy, fungal hyphae are seen in the stratum corneum. With routine staining, this finding may be quite subtle. Such special stains as the periodic acid-Schiff will help with the pathologic diagnosis. Additionally, the specimen may be cultured to identify the particular microorganism.3,4

The differential diagnosis includes common forms of dermatitis, including contact dermatitis, nummular dermatitis, atopic dermatitis, seborrheic dermatitis, and stasis dermatitis. Additionally, psoriasis and superficial staphylococcal infections (impetigo) may mimic tinea corporis.

Rarer diseases that may mimic tinea corporis include pityriasis rosea, erythema annulare centrifugum, subacute cutaneous lupus erythematosus, granuloma annulare, and parapsoriasis. Skin scrapings, culture, and biopsy can help distinguish tinea corporis from these other dermatoses when the diagnosis is in doubt.3,4

Topical antifungals are considered first-line therapy for limited disease. Selection of the topical antifungal is important, as the various medications do not have equal anti-dermatophyte potency. According to in-vitro studies, topical butenafine (Mentax) and terbinafine (Lamisil, Terbinex) are the most effective (butenafine may be more potent than terbinafine). Other therapies, in order of effectiveness, include ciclopirox (Penlac nail lacquer), naftifine (Naftin), and the topical azoles (e.g., clotrimazole, miconazole).5

In practice, many patients require systemic antifungal therapy with oral therapy (e.g., terbinafine or itraconazole [Sporanox]), especially for extensive disease or when there is a significant inflammatory component, such as in Majocchi’s granuloma or tinea profunda. Tinea corporis infections require a one- to two-week course of oral terbinafine or oral itraconazole.

Other treatment options include oral fluconazole (Diflucan) or griseofulvin for one to two weeks. In all cases, a full-body skin exam is warranted to identify other areas with tinea infection. For example, tinea infections of the nails will serve as reservoirs for reinfection, and require prolonged systemic therapy (i.e., 12 weeks of oral terbinafine).3,4,6

Treatment with systemic antifungal therapy requires an understanding of key medication interactions, as many patients are on multiple medications for such comorbidities as hypertension and hyperlipidemia. Some of the most common drug interactions that guide systemic antifungal selection include: terbinafine, contraindicated with all classes of beta-blockers; itraconazole, contraindicated with simvastatin (Zocor) and atorvastatin (Lipitor); and fluconazole, contraindicated with rosuvastatin (Crestor), fluvastatin (Lescol), and warfarin (Coumadin, Jantoven).

Griseofulvin is a CYP3A4 inducer and has the potential to lower the levels of multiple medications. Caution is advised with patients taking warfarin and such phosphodiesterase type 5 (PDE5) inhibitors as sildenafil (Revatio, Viagra), tadalafil (Adcirca, Cialis) and vardenafil (Levitra, Staxyn).4 This list is by no means comprehensive, and a thorough medication reconciliation is required when prescribing any systemic therapies.

In this case, the patient’s immunosuppressed status due to his poorly controlled diabetes and use of topical cortico­steroids likely contributed to his presentation of tinea corporis. He also had thickened yellowish dystrophic toenails with subungual debris, clinically indicative of tinea unguinum. He was treated with 12 weeks of oral terbinafine for tinea unguinum.

After the second week of therapy, the lesions on his trunk and extremities had cleared. Twelve months after therapy, the man’s toenails were completely clear of infection. Unfortunately, by 18 months after therapy, he had redeveloped a tinea infection in his toenails. This highlights the difficulty in maintaining remission in patients with diabetes and other immunosuppressive conditions.

Adam Rees, MD, is a first-year dermatology resident at Baylor College of Medicine in Houston.

References

  1. Borradori L, Bernard P. Pemphigoid group. In: Bolognia JL, Jorizzo JL, Rapini RP eds. Dermatology. 2nd ed. St. Louis, Mo.: Elsevier-Mosby; 2008:431-445.
  2. Chronic blistering dermatoses. In: James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders-Elsevier; 2011:448-467.
  3. Sobera, JO, Elewski BE. Fungal diseases. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, Mo.: Elsevier-Mosby; 2008:1135-1163.
  4. Diseases resulting from fungi and yeasts. In: James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders-Elsevier; 2011:287-321.
  5. Phillips RM, Rosen T. Topical antifungal agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 2nd ed. Philadelphia, Pa.: Saunders-Elsevier; 2007:547-568.
  6. Gupta AK. Systemic antifungal agents. In: Wolverton SE. Comprehensive Dermatologic Drug Therapy. 2nd ed. Philadelphia, Pa.: Saunders-Elsevier; 2007:75-99.
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