Jeffrey M. Weinberg

Cutaneous tuberculosis: diagnosis and treatment.

As we move into the 21st century, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multi-drug resistant pulmonary tuberculosis. Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG vaccine cause tuberculosis involving the skin.True cutaneous tuberculosis lesions can be acquired either exogenously or endogenously, show a wide spectrum of morphology and M. tuberculosis can be diagnosed by acid-fast bacilli (AFB) stains, culture or polymerase chain reaction (PCR). These lesions include tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and most cases of papulonecrotic tuberculid.The tuberculids, like cutaneous tuberculosis, show a wide spectrum of morphology but M. tuberculosis is not identified by AFB stains, culture or PCR. These lesions include lichen scrofulosorum, nodular tuberculid, most cases of nodular granulomatous phlebitis, most cases of erythema induratum of Bazin and some cases of papulonecrotic tuberculid.Diagnosis of cutaneous tuberculosis is challenging and requires the correlation of clinical findings with diagnostic testing; in addition to traditional AFB smears and cultures, there has been increased utilization of PCR because of its rapidity, sensitivity and specificity. Since most cases of cutaneous tuberculosis are a manifestation of systemic involvement, and the bacillary load in cutaneous tuberculosis is usually less than in pulmonary tuberculosis, treatment regimens are similar to that of tuberculosis in general.In the immunocompromised, such as an HIV infected patient with disseminated miliary tuberculosis, rapid diagnosis and prompt initiation of treatment are paramount. Unfortunately, despite even the most aggressive efforts, the prognosis in these individuals is poor when multi-drug resistant mycobacterium are present.An increased awareness of the re-emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasingly common skin disorder.

Severe cutaneous reactions associated with the use of human immunodeficiency virus medications.

Patients infected with human immunodeficiency virus are highly susceptible to adverse dermatological reactions to specific medications. Severe cutaneous conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis are associated with high morbidity and, notably for toxic epidermal necrolysis, high mortality. Although overall mortality from human immunodeficiency virus has dramatically declined owing to highly active antiretroviral therapy, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. We reviewed case reports and clinical trials in the English literature on Medline (1966 to 2001) and Aidsline (1980 to 2000) to determine the prevalence of Stevens-Johnson syndrome and toxic epidermal necrolysis attributable to the current FDA approved antiretroviral medications. We identified a total of approximately 50 patients who had Stevens-Johnson syndrome and/or toxic epidermal necrolysis associated with the use of 5 antiretroviral medications: 2 nucleoside reverse transcriptase inhibitors, zidovudine (2 patients) and didanosine (1 patient); 1 non-nucleoside reverse transcriptase inhibitor, nevirapine (42 patients); and 2 protease inhibitors, indinavir (1 patient) and amprenavir (an unspecified number within the 1% of over 1400 patients experiencing severe life-threatening reactions). Of the reports that specified the onset time of adverse reaction after initiation of treatment, 86% (19/22) of patients experienced reactions within 4 weeks. Ten of the approximately 50 patients were diagnosed with Stevens-Johnson syndrome or toxic epidermal necrolysis, due to specific antiretroviral medication, or a combination of medications identified by either resolution upon withdrawal, consistent biopsy findings or a positive rechallenge. The remainder of the identified patients were reported in articles lacking data regarding drug administration, reaction history or other details.

Viral Folliculitis: Atypical Presentations of Herpes Simplex, Herpes Zoster, and Molluscum Contagiosum

BACKGROUND Viral folliculitis is an infrequently reported entity. The patients described herein were seen over a 12-year period of practice in a referral dermatologic setting. The cases involve a variety of viral infections limited to the hair follicle. OBSERVATIONS We describe 5 patients with a variety of viral folliculitides: 2 with herpetic sycosis caused by herpes simplex; 1 with herpex simplex folliculitis (this patient also had human immunodeficiency virus); 1 with herpes zoster without blisters; and 1 with molluscum contagiosum. CONCLUSIONS These 5 cases demonstrate that viral folliculitis has varied causes and presentations. Clinicians should consider viral agents in the differential diagnosis of superficial infectious folliculitis, especially in cases that are refractory to antibacterial or antifungal therapy.

Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus.

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to review the progress of the biologic agents which are available, or under investigation for clinical use: infliximab, etanercept, efalizumab, alefacept, and adalimumab. In addition, two other investigational therapies, oral tazarotene and oral pimecrolimus will be discussed. Clinical data for these agents, including the most recent phase II and/or III study results, will be discussed, as well as the most recent safety data.

Cutaneous Paecilomyces lilacinus infection: Report of two novel cases

A 56-year-old white man had painful skin lesions on his left leg 10 months after a liver transplant. His medications included prednisone, tacrolimus, azathioprine, trimethoprim-sulfamethoxazole, acyclovir, and granulocyte-macrophage colony-stimulating factor. Examination revealed multiple crusted and violaceous papules, plaques and nodules extending from the dorsal aspect of the left foot to the left knee (Fig. 1). He had a leukocyte count of 2.8 xl03/g 1 and a hematocrit of 27.6%. A biopsy specimen revealed findings consistent with a deep fungal infection. Fungal cultures of bone marrow and blood were negative. The patient received a 2-week course of intravenous amphotericin B with subsequent oral itraconazole, 400 mg daily. About a year later, he was readmitted because of a cellulitis and persistent deep fungal infection of the left leg. The patient was treated with oral itraconazole, but the infection persisted. Lesions extended from the dorsal aspect of the left foot to the left upper thigh. A culture grew P. lilacinus. A biopsy specimen demonstrated granulomatous and suppurative dermatitis. A periodic acid-Schiff stain demonstrated fungal spores and hyphae within the dermal granuloma. Oral itraconazole was stopped and the patient was again given intravenous amphotericin B but experienced no improvement. With

Utility of histopathologic analysis in the evaluation of onychomycosis.

Onychomycosis is a common problem seen in clinical practice. Given the differential diagnosis of dystrophic nails, it is helpful to obtain a definitive diagnosis of dermatophyte infection before initiation of antifungal therapy. Potassium hydroxide preparation and fungal culture, which are typically used in the diagnosis of these infections, often yield false-negative results. Recent studies have suggested that nail plate biopsy with periodic acid-Schiff stain may be a very sensitive technique for the diagnosis of onychomycosis. In this article, we review the literature on the utility of histopathologic analysis in the evaluation of onychomycosis. Many of these studies indicate that biopsy with periodic acid-Schiff is the most sensitive method for diagnosing onychomycosis. We propose that histopathologic examination is indicated if the results of other methods are negative and clinical suspicion is high; therefore, it is a useful complementary technique in the diagnosis of onychomycosis.

Study of Clinically Suspected Onychomycosis in a Podiatric Population

Onychomycosis, by definition, is a mycotic infection of the keratinized tissue of the nail plate. Although it is commonly considered to be caused by one of the dermatotropic fungi, a variety of other organisms have been implicated as etiologic agents in the disease, including some bacteria and yeasts. When it is caused by a fungus, any or all of three types of organisms can be involved: dermatophytes, yeasts, and nondermatophyte organisms. The purpose of this study was to identify the microorganisms found in fungal cultures of clinically suspected onychomycosis in the patient population of the Foot Clinics of New York in New York City, the largest foot clinic in the world. Of the 1,800 medical charts reviewed, 214 had culture results, of which 120 were positive. Trichophyton rubrum was the most prevalent pathogen, found in 67% of positive cultures. The most remarkable risk factor was age, with 80% of affected individuals older than 35 years. False-negatives may account for the high percentage (44%) of negative cultures in this study.

Extensive calcinosis cutis in association with systemic lupus erythematosus.

Sir, Calcium deposits in the skin sometimes occur is association with certain connective tissue diseases, particularlyscleroderma and dermatomyositis (1). This ® nding is extremely rare in systemic lupus erythematosus (SLE) (2). In most cases of calcinosis cutis in SLE, the deposition of calcium is usually seen under the cutaneous lupus lesions, and the amounts are relatively small. We report here a 49-year-oldwoman featuring SLE with extensive subcutaneous and muscular calci® cations. Over time, the calci® cation became more diŒuse and extended into the subcutaneous and muscular layer of her pelvis and extremities, forming large plate-like calci® cations. Only 16 such cases of extensive calcinosis cutis in SLE have been reported in the literature (3± 12).

PROXIMAL WHITE SUBUNGUAL ONYCHOMYCOSIS IN THE IMMUNOCOMPETENT PATIENT : REPORT OF TWO CASES AND REVIEW OF THE LITERATURE

Sir, Proximal white subungual onychomycosis (PWSO) is the rarest subtype of onychomycosis (1). In PWSO, the infection begins with fungal invasion of the stratum corneum of the proximal nail fold, followed by infection of the deeper portions of the nail plate. This presentation of onychomycosis is most commonly caused by T. rubrum; other common causative agents include T. megninii, T. schoenleinii, T. tonsurans, T. mentagrophytes, and E. £occosum (1, 2). The majority of initial cases of PWSO reported were patients with AIDS (1 ^ 3). In one study, 55 of 62 HIV-infected patients with onychomycosis (83.7%) had PWSO (4). In more than half of these patients (58%), T. rubrum was the etiologic agent. PWSO has also been reported in patients with other immunode¢ciencies, including a renal transplant recipient on immunosuppressive therapy (5), and a patient with systemic lupus erythematosus on systemic steroids (6). In addition, Baran (7) described a case of proximal subungual candida onychomycosis as a manifestation of chronic mucocutaneous candidiasis. Recently, however, there have been several reports of immunocompetent patients developing PWSO (8 ^ 10). We now report two immunocompetent patients with proximal white subungual disease, and review the other cases described, emphasizing that not all patients with this presentation are immunode¢cient.

Treatment of tufted angioma with interferon alfa: role of bFGF.

To the Editors: Tufted angioma was first described in 1989 by Wilson Jones and Orkin (1) as a distinct vascular lesion that is characterized by circumscribed lobules of hypertrophied capillaries with a pericyte component. Tufted angiomas most commonly arise on the neck and upper trunk in young persons. Over half of patients develop the lesions within the first 5 years of life, and only three patients previously reported have had lesions at birth. These lesions typically undergo a growth phase, characterized by lateral extension, for 5 months to 10 years (2). Treatment of tufted angioma is usually unsatisfactory. Recently Suarez et al. (2) reported a good response to treatment with interferon alfa. Despite low initial levels of urinary bFGF, a successful trial of interferon alfa was initiated. We report a patient with a tufted angioma and elevated urinary bFGF who underwent a trial of interferon alfa. The patient demonstrated a marked decrease in urinary bFGF levels, but no clinical response. This observation indicates that other growth factors in addition to bFGF contribute to the development of tufted angiomas. A 12-year-old white girl presented for evaluation of a congenital lesion involving her right thigh. The lesion had significantly increased in size over a 2-year period. The patient had no additional past medical history. On physical examination, a 15 cm x 15 cm, nontender, purple plaque was present on the right anterior and lateral thigh and knee. Both limbs were of equal circumference. No bruits or thrills were detected at the site. A biopsy specimen of the lesion revealed focal collections of tightly packed capillaries throughout the dermis. Multiple rounded lobules of poorly canalized capillary channels were widely distributed. Baseline MRI revealed vascular proliferation limited to the subcutaneous fat without extension into the muscle layers, synovial space, or bone structure. However, the subcutaneous fat layer was enlarged as a result of increased vascular volume present in the area. The patient was referred to hematology/oncology for a trial of interferon alfa. Baseline urinary bFGF level was 4500 pg/g Cr. She received a total course of 12 weeks of daily subcutaneous injections of interferon alfa 2 to 3 Mu/m2 without significant change in the size of the lesion over a 3-month period. Two urinary bFGF levels of less than 500 pglg Cr were obtained while the patient was on treatment, which were significantly less than her baseline level. Many treatments have been used for tufted angioma, including surgical excision, x-ray therapy, dye laser, cryosurgery, and electrocautery, all of which have been associated with recurrences of the lesion (2). Treatment with topical or intralesional corticosteroids has been reported to have no effect. Interferon alfa has been shown to dramatically decrease the size of cutaneous hemangiomas in expanding lesions (3), and Suarez et al. (2) applied this therapy successfully in the treatment of tufted angioma. In addition to this case, there is one further case of successful treatment with interferon alfa (4), although one case failed to respond to subcutaneous injections (5 ) and one to intralesional injections of interferon alfa (6). Levels of urinary bFGF are often elevated in patients with significant capillary proliferation, as in early hemangioma, and tend to diminish to normal during treatment with interferon alfa. Our patient had an initial bFGF level of 4500 pg/g Cr which decreased to less than 500 pg/g Cr after treatment with interferon alfa. However, despite this decrease, our patient failed to demonstrate any resolution of the lesion. In the case of Suarez et al. (2), interferon was successful despite normal bFGF levels. Both of these cases suggest that other factors are involved in the pathogenesis and regulation of capillary proliferation in tufted angiomas and that further investigation is required to elucidate its pathophysiology. This will enable the formulation of better therapeutic options.