Diagnosis and management of vulvar cancer: A review.

Vulvar malignancies represent a serious gynecologic health concern, especially given the increasing incidence over the past several decades. Squamous cell carcinoma and melanoma are common subtypes, although other neoplasms, such as basal cell carcinoma and Paget disease of the vulva, might be seen. Many vulvar cancers are initially misdiagnosed as inflammatory conditions, delaying diagnosis and worsening prognosis. It is essential that dermatologists are familiar with characteristic findings for each malignancy to ensure appropriate diagnosis and management. Herein, we review the unique epidemiologic and clinical characteristics of each major vulvar malignancy, as well as discuss their respective prognoses and current management recommendations.

Levamisole toxicity mimicking autoimmune disease.

BACKGROUND: Levamisole is present as a contaminant or additive in most cocaine sold in the United States. Cases of agranulocytosis attributed to levamisole-tainted cocaine have been widely described. A vasculopathic reaction to levamisole has also been reported; however, diagnostic features such as antineutrophil cytoplasmic antibody (ANCA) and additional autoimmune marker positivity are not well recognized. As such, many patients are given a misdiagnosis, prompting aggressive and often unnecessary treatment. OBJECTIVE: We hope to educate practitioners about the clinical and laboratory features of levamisole-induced vasculopathy to ensure accurate diagnosis and management. METHODS: This was a case series. RESULTS: Six patients were admitted with purpuric lesions and vasculitic changes on biopsy specimen; 5 of them were given the diagnosis of and treated for autoimmune conditions before their true diagnosis was revealed. All patients had ANCA positivity, and 4 had additional abnormalities in autoimmune markers. All patients reported recent cocaine abuse, and were ultimately given the diagnosis of levamisole-induced vasculopathy. LIMITATIONS: This observational study is limited by sample size. CONCLUSIONS: Patients presenting with purpuric lesions with ANCA positivity should be assessed for cocaine exposure. It is important to recognize that levamisole may not only induce ANCA positivity but also other autoimmune marker abnormalities. Patients can often be treated with less aggressive therapeutic strategies than what is used for primary ANCA-associated vasculitides.

Chronic lymphocytic leukemia and the skin: implications for the dermatologist.

B-cell chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United States, and its diagnosis can have many dermatologic implications. For one, the cutaneous manifestations of CLL include several entities, most notably leukemia cutis, eosinophilic dermatosis of hematologic malignancy, and a heightened risk of skin infections. Additionally, CLL patients are at an increased risk of secondary malignancies, most commonly of the skin. Furthermore, a number of commonly utilized treatments for CLL have cutaneous implications which should be considered in the interdisciplinary management of CLL patients. In this review, we will provide an update on the diverse cutaneous manifestations of CLL and CLL-directed therapies in order to help guide dermatologic management of this increasingly prevalent patient population.

Viral Venereal Diseases of the Skin.

Viral venereal diseases remain difficult to treat. Human papilloma virus (HPV) and herpes simplex virus (HSV) are two common viral venereal diseases. HPV infections are characterized by anogenital warts and less commonly by premalignant or malignant lesions. HSV infections classically present as grouped vesicles on an erythematous base with associated burning or pain; however, immunosuppressed patients may have atypical presentations with nodular or ulcerative lesions. This review discusses the epidemiology, diagnosis, and management of anogenital HPV and HSV infections with an emphasis on treatment modalities for the practicing dermatologist. Diagnosis of these diseases typically relies on clinical assessment, although multiple diagnostic techniques can be utilized and are recommended when diagnosis is uncertain or evaluating an individual with increased risk of malignancy. Management of HPV and HSV infections involves appropriate counseling, screening, and multiple treatment techniques. Particularly for HPV infections, a practitioner may need to use a combination of techniques to achieve the desired outcome.

Dermatologic sequelae of breast cancer: From disease, surgery, and radiation.

The care of breast cancer patients is important to dermatologists. Breast cancer's initial presentation, clinical progression, and its associated treatments can result in a variety of cutaneous complications. Dermatologists may be the first to identify a breast cancer diagnosis, as a subset of patients first present with direct extension of an underlying tumor or with a cutaneous metastasis. The surgical treatment of breast cancer also begets a variety of skin sequelae, including postoperative lymphedema, soft tissue infections, seromas, pyoderma gangrenosum, and scarring disorders. Moreover, breast cancer radiation treatment commonly results in skin changes, which can range from mild and temporary dermatoses to chronic and disfiguring skin ulceration, fibrosis, and necrosis. Radiation may also precipitate secondary malignancies, such as angiosarcoma, as well as rarer dermatologic diseases, such as radiation-induced morphea, lichen planus, and postirradiation pseudosclerodermatous panniculitis. Finally, breast cancer is also associated with an array of paraneoplastic phenomena, including Sweet's syndrome and the rarer intralymphatic histiocytosis. Herein, we review the dermatological manifestations of breast cancer, including conditions associated with its presentation, progression, and treatment sequelae. Chemotherapy-induced cutaneous side effects are beyond the scope of this review. This article provides a comprehensive review for dermatologist to be able to identify, diagnose, and manage breast cancer patients from initial presentation to treatment monitoring and subsequent follow-up.

Art of prevention: The importance of dermatologic care when using aromatase inhibitors.

As of January 2021, there are more than 3.8 million women in the United States with a history of breast cancer. The current standard of care for breast cancer involves surgical resection, radiation therapy, adjuvant endocrine therapy, and/or adjuvant chemotherapy. Aromatase inhibitors (AIs) are the gold standard for endocrine therapy in postmenopausal women. Dermatologic adverse events (dAEs) associated with AIs are rare but have been reported in the literature. Commonly reported dAEs include unspecified rash, pruritus, alopecia, vulvovaginal atrophy, vasculitis, and autoimmune/connective tissue disorders. Appropriate preventative strategies and careful management considerations have the potential to optimize the comprehensive care of patients with cancer and improve quality of life. Furthermore, prevention of dAEs can lead to a reduction in cancer treatment interruptions and discontinuations. Herein, we characterize dAEs of AIs and discuss preventative management to reduce the incidence of AI therapy interruption.

Systemic drug-related intertriginous and flexural exanthema (SDRIFE).

A 72-year-old man with a history of metastatic melanoma presented with a two-day history of erythematous and edematous plaques, with scattered bullae on the neck, chest, axillae, and inguinal and gluteal folds, which began five days after infusion of an experimental drug. The clinical and histopathologic findings were consistent with systemic drug-related intertriginous and flexural exanthema (SDRIFE), which is an uncommon drug reaction that results in symmetric erythema that affects the buttocks, groin, and/or thighs as well other flexural folds. The clinical manifestations of SDRIFE are highly characteristic and include distinctive primary cutaneous lesions with a specific distribution and course; however, heterogeneity exists with respect to histopathologic features, skin test results, and in vitro investigations. The exact mechanism of SDRIFE remains unknown but is thought to result from a type IV delayed hypersensitivity immune response. Treatment is symptomatic and includes topical or oral glucocorticoids.

Palisaded neutrophilic and granulomatous dermatosis.

A 22-year-old woman with mixed connective-tissue disease presented with a 5-month history of recurrent episodes of tender, erythematous papules, nodules, and edematous plaques on the upper extremities and thighs. Cutaneous lesions occurred in the setting of livedo reticularis. A biopsy specimen showed interstitial and perivascular inflammation with lymphocytes, macrophages, neutrophils, nuclear dust, collagen alteration, extravasated erythrocytes, and fibrin within small superficial blood vessels. These changes were consistent with a diagnosis of palisaded neutrophilic and granulomatous dermatosis, which is a rare entity that includes a combination of a neutrophilic infiltrate, abnormal or altered collagen, granuloma formation, and leukocytoclastic debris in the context of an immune-mediated collagen vascular or systemic disease. The underlying mechanism remains poorly understood. Treatment is limited, and resolution of lesions typically occurs within several months to years.

Perforating collagenosis.

A 55-year-old man presented with a three-week history of pruritic, erythematous papules with hyperkeratotic dells on the dorsum of the left hand, which was preceded by swelling, redness and itching. Histopathologic examination showed an acanthotic epidermis with a central invagination filled with a plug composed of parakeratotic debris, collagen, and inflammatory cells. These findings are consistent with acquired reactive perforating collagenosis, which is most frequently reported in patients with pruritus and underlying diabetes mellitus or chronic renal insufficiency. Topical and oral retinoids and topical and intralesional glucocorticoids have been reported to be effective in some patients in case series.

Mastocytosis with urticaria pigmentosa and osteoporosis.

A 76-year-old man with a 52-year history of urticaria pigmentosa was found to have an elevated serum tryptase level as well as osteoporosis. Histopathologic alterations of one his skin lesions showed an infiltrate of mast cells. Urticaria pigmentosa patients are at risk for osteoporosis because of elevated heparin and stem-cell factor levels. These patients should be screened with serum tryptase levels and bone density studies to detect osteoporosis, regardless of their age.

Unilateral nevoid telangiectasia.

A 30-year-old woman, who was six months pregnant, presented with multiple, blanching, asymptomatic telangiectasies on her right upper extremity for two years. At the onset of her pregnancy, her lesions increased in number and redness. Given the unilateral distribution and worsening during pregnancy, a diagnosis of unilateral nevoid telangiectasia was made. This condition is a rare entity that has been most commonly reported in association with puberty, pregnancy, the use of oral contraceptives, and alcoholic cirrhosis. However, there have been case reports in otherwise healthy individuals.

Lichen planopilaris and psoriasis.

A 34-year-old woman presented with large, scaly patches of alopecia with a peripheral rim of violaceous, folliculocentric papules and appreciable pruritus of one-year duration. Histopathologic examination showed changes consistent with lichen planopilaris and psoriasis, which was suggested by neutrophilic spongiosis. Consequently, cyclosporine and betamethasone valerate topical 0.12 percent foam twice daily were initiated. A short time after, there was clinical reduction of perifollicular erythema and attenuation of pruritus. However, there was no decrease of scale. Although LLP is classified in the lymphocytic group of cicatricial alopecias, this case demonstrates a clinical and histopathologic overlap with a psoriasiform dermatosis which may represent a collision of two diseases.

Epidermodysplasia verruciformis in the setting of HIV infection.

A 56-year-old man with human immunodeficiency virus infection presented with pink-to-hypopigmented, thin, flat-topped papules coalescent to plaques on the trunk and extremities for five years. The histopathologic findings were consistent with flat warts resembling epidermodysplasia verruciformis. Typically an inherited condition, this entity has also been observed in the setting of immunosuppression; the risk of developing non-melanoma skin cancers is of concern. Treatment options vary considerably, but often the lesions will recur upon cessation of therapy.

Chronic cutaneous lupus erythematosus in vitiligo.

A 49-year-old woman presented with a seven-year history of pruritic, erythematous, scaling plaques on sun-exposed skin that localized only to pre-existing depigmented patches. Histopathologic examination showed changes consistent with cutaneous lupus erythematosus with lichenoid features and confirmed contiguous vitiligo. Diagnosis of chronic cutaneous lupus erythematosus localized to areas of vitiligo was determined by clinicopathologic correlation and may reflect an autoimmune diathesis. Consequently, hydroxychloroquine and topical glucocorticoids therapy were initiated with reported improvement in pruritus, erythema, and scale. Clinical monitoring for development of squamous-cell carcinoma in areas of chronic inflammation and sun-exposure is imperative.

Erythema elevatum diutinum.

A 64-year-old woman presented with a one-and-one-half year history of an enlarging, red-brown, firm plaque on the left thigh, with numerous, scattered, indurated, hyperpigmented patches on the lower extremities. Histopathologic examination of the largest plaque confirmed the diagnosis of erythema elevatum diutinum, which is a rare form of leukocytoclastic vasculitis that is associated with many disease entities, which include human immunodeficiency virus infection, malignant conditions, hematologic abnormalities, chronic infection, and autoimmune and connective-tissue disorders. The treatment of choice is dapsone; however, several other treatment modalities have been reported to be of benefit.

Invasive squamous-cell carcinoma and arsenical keratoses.

A 42-year-old man presented with a six-month history of a slowly-enlarging ulcer on his right sole, a 30-year history of altered pigmentation of the trunk and extremities, and hyperkeratotic papules of the palms and soles. Histopathologic examination showed an invasive squamous-cell carcinoma of the right sole and hyperkeratosis with keratinocyte atypia of the left finger and left lateral foot. The clinical and histopathologic findings are consistent with chronic arsenicism, which most commonly occurs in the setting of drinking contaminated water or after occupational exposure. Evaluation should include a physical examination, basic laboratory work-up, and measurement of a 24-hour urine arsenic concentration. Vigilant surveillance for the development of cutaneous malignancies is required. Oral retinoids may be helpful in reducing hyperkeratosis secondary to chronic arsenicism.

Delayed cutaneous reactions to iodinated contrast.

Iodinated contrast (IC) often is overlooked as a cause of delayed drug reactions. As a result, patients may continue to be readministered these agents, experiencing preventable morbidity. We report an illustrative case of a delayed cutaneous reaction to IC and review the literature on the epidemiology and management of this underrecognized phenomenon.