Incidence of adverse cutaneous drug reactions in a Mexican sample: an exploratory study on their association to tumour necrosis factor alpha TNF2 allele.

BACKGROUND: Most adverse cutaneous drug reactions (ACDR) are mediated by delayed hypersensitivity (dh) with lymphocyte recruitment and inflammatory cytokines release, including tumour necrosis factor alpha (TNFalpha). Polymorphisms in the TNFalpha gene, such as the infrequent allele TNF2, predispose to certain inflammatory entities and enhance TNFalpha production. The incidence of the TNF2 allele is increased in British patients with severe ACDR, suggesting TNFalpha as a major contributor in the pathogenesis of ACDR. OBJECTIVE: We designed a prospective study to analyse the epidemiology of ACDR in a third-level Mexican hospital and explore the possibility of a relationship between the TNF2 allele and ACDR-dh. METHODS: A prospective study during 9 months allowed recognition of 34 ACDR-dh patients. The study included 33 paired patients, and 44 healthy volunteers. All subjects were genotyped for TNF2 by PCR DNA amplification and NcoI restriction endonuclease digestion. Results Incidence of ACDR was 0.95%. The TNF2 allele was detected in 9.9% of the sample population with no significant differences between healthy controls, and patients with or without ACDR-dh. Only 3 of the 34 ACDR-dh subjects presented severe reactions, with 1 having the TNF2 allele. Comorbidity analysis showed significance only with autoimmune thyroid disease, consistent with reports on Chinese and Tunisian patients. CONCLUSION: ACDR incidence and TNF2/TNFA heterozygosity were lower in Mexican than in Caucasian patients. ACDR-dh patients showed no increased frequency in the TNF2 allele.

Membrane glycoconjugate visualization and biosynthesis in normal and retinoid-treated epidermis.

Cell-membrane glycoconjugates can be visualized for ultrastructural and fluorescence studies with certain surface markers, such as lectins and antisaccharide antibodies. When frozen sections of mammalian epidermis are treated with a battery of rhodamine-conjugated lectins, the cell membranes display a pattern of increased sugar complexity during keratinocyte maturation. Although this vectorial sequence is disrupted following retinoid treatment, these changes occur only at high doses and late in the course of treatment, suggesting that retinoid-induced alterations may be secondary. Seemingly as a result of specific glycosidase activity within the cytosol of both granular and cornified cells, lectin staining suddenly disappears from stratum corneum cell membranes. Although lectins stain membrane glycoconjugates of cultured human keratinocytes, quantitative techniques are required to recognize differences in proliferating versus postmitotic cells and in cultures supplemented with various growth factors. Whereas retinoids consistently depress glycoprotein synthesis in cultured keratinocytes, in organ culture they stimulate epidermal glycoprotein, and particularly glycolipid, biosynthesis. These studies suggest (1) that visualization of membrane glycoconjugates with lectins can reveal important variations in normal and pathologic epidermal differentiation, (2) that lectins may reveal subtle quantitative alterations in differentiation in vitro, (3) that retinoid stimulation of glycoconjugate biosynthesis either displays important species differences or requires a higher level of organization than occurs in cell culture, and (4) that the retinoid effect on glycoconjugate biosynthesis in organ culture may provide another useful bioassay for retinoid potency.

Safety and efficacy of Virend for topical treatment of genital and anal herpes simplex lesions in patients with AIDS.

Virend (SP-303), a new topical antiviral agent with activity against herpesvirus, was evaluated in a multicenter, double-blind, placebo-controlled Phase II study for safety and effectiveness against recurrent genital herpes lesions in patients with AIDS. The primary endpoints of this study were complete healing of lesions and time to healing. Patients had a history of recurrent genital or anogenital herpes with at least one lesion and positive HSV culture at enrollment. Participants received Virend (15% ointment; 24 patients) or matching placebo (21 patients) three times a day for 21 days. Excluding two patients in the Virend group who received an initial treatment but were lost to follow-up, 9 of 22 (41%) patients treated with Virend experienced complete healing of their lesions compared with three (14%) patients in the placebo group (P = 0.053). Viral culture revealed that 50% of Virend-treated patients and 19% of placebo-treated patients became culture-negative during treatment (P = 0.06). Based on these preliminary clinical findings, further evaluation of Virend for topical treatment of genital herpes in patients with AIDS is planned.

Elevated Th1 cytokine mRNA in skin biopsies and peripheral circulation in patients with erythema nodosum.

It is generally believed that erythema nodosum is the result of an immunologic attack centered within the subcutaneous fat. This belief, however, is based on indirect evidence. The aim of this study was to analyze whether erythema nodosum could represent an example of a polarized Th1 or Th2 immune response. We have studied herein, by semiquantitative coupled reverse transcription-polymerase chain reaction the Th1 (IL-2, IFN-gamma) and Th2 (IL-4, IL-10) cytokine gene expression in skin biopsies and peripheral blood from eleven patients with erythema nodosum. As controls, we studied skin and peripheral blood from nine healthy subjects. We found expression of Th1 cytokines in most erythema nodosum skin lesions as well as in their peripheral blood. Both Th1 and Th2 cytokine gene expressions were scarcely or not detected in the skin and peripheral blood of control subjects. These results directly demonstrate that a polarized Th1 immune response occurs in the skin lesions of erythema nodosum patients regardless of the wide variety of provoking agents.

[Cutaneous histoplasmosis in nine patients with AIDS]. / Histoplasmosis cutánea en nueve pacientes con SIDA.

UNLABELLED: In AIDS patients the diagnosis of systemic mycosis is a clinical challenge. When cutaneous affection occurs, the diagnosis is difficult because of the non-specific clinical findings. We describe nine patients with AIDS and cutaneous histoplasmosis as the initial clinical manifestation. These patients were diagnosed from 1987 to 1998. In all the diagnosis of histoplasmosis was done by skin biopsy and fungal isolation. The main skin lesions were papules combined with pustules or nodules in 6 of 9 patients, ulcers (1/9), erythematous plaques (1/9) and nodules (1/9). Head and trunk were the main anatomical locations of the lesions. All had fever, 7/9 had liver and spleen enlargement and 5/9 had weight loss. At the time of diagnosis all patients had a low CD4+ lymphocyte counts with a mean of 47 cells/microL. Amphotericin B was the initial treatment followed by itraconazole. Five patients died, one day after diagnosis and four after 5, 8, 11 and 12 months. Four are alive at 3, 3, 19 and 26 months of follow-up. CONCLUSIONS: In AIDS patients the skin involvement by histoplasmosis should always be included among the differential diagnoses specially in patients with face and trunk papules and fever and hepatosplenomegaly. Skin and bone marrow cultures were the most reliable diagnostic methods, but skin biopsy was the fastest procedure.

Two cases of psychogenic purpura.

Psychogenic purpura, also known as recurrent painful bruising or autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome) is usually associated with emotionally disturbed patients. It is a troublesome entity for both patient and physician since extensive work-ups yield no diagnosis. We describe two females in their early twenties with recurrent painful bruising and diverse accompanying symptoms which appeared after physical trauma. One of the patients developed a bruise after intradermal injection of her own blood (with no reaction to saline injection). One patient had a personality (borderline) disorder, the other a factitious disorder. Punch biopsies revealed a perivascular inflammatory infiltrate, erythrocyte extravasation and no vasculitis. Psychogenic hemorrhagic disorders are uncommon yet must be considered in the differential diagnosis of purpura. Patients are usually young emotionally troubled females who present painful recurrent bruises on extremities frequently after trauma or surgery. Autoimmune mechanisms and increased cutaneous fibrinolytic activity have been implicated, although further studies are needed. Correct diagnosis is important to avoid aggressive and even mutilating treatments, and an adequate comprehension of these purpuras is important for the attending physician.

[Hypersensitivity syndrome caused by allopurinol. A case of massive hepatic necrosis]. / Síndrome de hipersensibilidad por alopurinol. Un caso de necrosis hepática masiva.

Adverse drug reactions have a wide variety of clinical manifestations mainly related to the affected organ. The skin is one of the most common organs involved due to the visibility of the lesions to the observer. These untoward drug cutaneous responses may mimic any known dermatosis, and may be a clue to a serious systemic disease. We present the case of a 72 year-old woman with erythema multiforme, liver and renal failure due to a unknown dosage of allopurinol self-medication for two weeks. The clinical course was characterized by a Stevens-Johnson syndrome and severe drug-induced liver disease with massive hepatic necrosis corroborated by a transjugular liver biopsy; finally she died of gastrointestinal bleeding. Consent for a postmortem study was not obtained. The clinical course as well as the cutaneous, renal and hepatic drug-related complications corresponds to an allopurinol hypersensitivity syndrome. The relevance of this case was the extension of the liver damage apparently due to the allopurinol, which is an infrequent hepatotoxic complication. In some cases, like the present case, it can be a serious and fatal complication.

Clinical, histopathological, immunological and fibroblast studies in 30 patients with subcutaneous injections of modelants including silicone and mineral oils.

OBJECTIVE: To study patients with side effects secondary to the injection of modelants. METHODS: We studied their clinical, serological, histopathological, radiographic, immunoregulatory and fibroblast culture features by standard methods. We studied thirty patients, 24 women, mean age: 38.2 years. Patients had received either mineral oil, guayacol, silicone or a mixture of these substances; some had received unknown material(s). RESULTS: The mean time between the injection and the onset of symptoms was six years (range: 0.1-24 years). All patients had sclerodermatous skin changes, subcutaneous nodules, edema and/or hyperpigmentation at the site(s) of injection(s); five individuals also had skin changes at sites remote from the injection. Thirteen patients had clinical features of an autoimmune disease. Eleven patients gave a history of arthralgias including four that had symmetrical non-erosive polyarthritis. Twenty of 28 patients (71%) had positive anti-nuclear antibodies. We found intracellular spontaneous production of IL-1 (interleukin-1) by patients' macrophages which was almost absent in normal cells (p < 0.001). Silica-stimulated monocytes from patients also secreted more IL-1 than those from normal subjects (p < 0.001) in autologous mixed lymphocyte reaction. Twelve patients had an early proliferative response. At day seven, a decreased proliferative response was seen in 12/19 patients (p < 0.001). Skin fibroblasts from 3/3 patients synthesized 3-to-5-fold more 3H-hyaluronic acid than normal control cells (p < 0.001). CONCLUSIONS: This report confirms the association between the injection of modelants and the development of autoimmune disease (human adjuvant disease, HAD). Our results implicate IL-1 in the amplification of the disease process. The similarities between primary scleroderma and human adjuvant disease now include immunological and connective tissue data. The study of these patients may help to understand the etiopathogenesis of some autoimmune diseases.

Frequency of oral conditions in a dermatology clinic.

BACKGROUND: Oral mucosal manifestations may be the initial feature, the most florid clinical feature, or the only sign of mucocutaneous diseases. METHODS: Sixty adult patients (48 women, 12 men) with oral mucous complaints were referred to and evaluated at a dermatology clinic in a tertiary care hospital in Mexico City between November 1996 and September 1998. RESULTS: The most frequent oral conditions observed were pemphigus vulgaris (18.3%), lichen planus (8.3%), candidiasis (8.3%), recurrent aphthous ulcers (6.7%), herpetic lesions (6.7%), xerostomia (6.7%), and traumatic lesions (6.7%). Oral affection in mucocutaneous conditions was observed in 21 (35%) patients; the diagnosis was based on oral signs in 10 (48%) of these patients. A large number of oral conditions had previously been misdiagnosed. CONCLUSIONS: The importance of the diagnosis of oral conditions in dermatology has been underlined in this study due to the frequency and diversity of oral lesions. The benefits of an interdisciplinary approach in the management of patients has been highlighted.

Oral manifestations as a hallmark of malignant acanthosis nigricans.

We present a case of malignant acanthosis nigricans (AN) that initially manifested in the oral cavity. In the present report, the patient had typical clinical and histological findings of oral and esophageal AN, with subtle skin changes, associated with a gallbladder adenocarcinoma. The importance of the clinical oral examination is emphasized because the recognition of oral lesions led to the diagnosis of AN and to the following detection of the internal malignancy. Since the tumours associated with AN are highly malignant, it is of the utmost importance to recognize the skin and mucous membrane changes in adults.

Necrolytic migratory erythema: a cutaneous clue to glucagonoma syndrome.

Necrolytic migratory erythema (NME) is a cutaneous manifestation of the glucagonoma syndrome. We present a case with a pancreatic glucagon-secreting tumour, skin eruption and a good response to treatment.

Dermatoses in 156 obese adults.

BACKGROUND: Skin diseases are mentioned as a frequent finding in the obese patient. However, to our knowledge no study has been done on this subject. OBJECTIVE: To determine the prevalence of skin diseases associated with different obesity grades and if any dermatosis can be considered an obesity marker. MATERIALS AND METHODS: A cross-sectional study of 156 obese patients who were 110% to 293% overweight were included. Complete medical history and dermatological examination were done. RESULTS: In the 126 female and 30 male obese patients, grades I to V, with a body mass index (BMI) of 27-51, cutaneous findings with statistical significance for linear trend were: plantar hyperkeratosis 54 patients p = 0.00001; acanthosis nigricans 46 patients p = 0.00005; striae 67 patients p = 0.03; skin tags 69 patients p = 0.01; keratosis pilaris 33 patients p = 0.007. Patients with plantar hyperkeratosis were distributed in the obesity groups as follows: grade I = 3 patients; grade II = 7 patients; grade III = 8 patients; grade IV = 17 patients; and grade V = 19 patients. Of the 76 diabetic patients, 26 had acanthosis nigricans, 38 had skin tags, and 27 had plantar hyperkeratosis. DISCUSSION: Plantar hyperkeratosis should be considered as a cutaneous stigma of severe obesity. This is probably a result of pressure directly related to the excess weight.

An epidemic outbreak of Malassezia folliculitis in three adult patients in an intensive care unit: a previously unrecognized nosocomial infection.

BACKGROUND: Malassezia is a lipophilic fungus commonly found in normal human skin. Infection of the hair follicle by Malassezia furfur occurs in patients with predisposing factors such as diabetes or immunosuppression, or who are undergoing antibiotic treatment. Malassezia furfur folliculitis is an infrequent nosocomial infection which may be associated with fomite transmission. METHODS: We reviewed the clinical files of three adult patients from an intensive care unit (ICU) who simultaneously developed folliculitis through Malassezia infection. We specifically analysed predisposing factors, possible transmission modes, characteristics of skin lesions, results of biopsies and cultures, treatment, and patient outcome. RESULTS: The three male patients were in neighboring beds and they all had factors that predisposed them to underlying immunosupression. Simultaneously, and within hours of each other, they developed erythematous follicular papules and pustules on the face and chest. The skin biopsies revealed an acute folliculitis with abundant round to oval yeasts of up to 5 microm in diameter. Stains for fungi (Schiff's peryodic acid, Grocott and silver methenamine) revealed numerous unipolar budding yeasts without hyphae, consistent with M. furfur. Conventional cultures were negative. The diagnosis of folliculitis by M. furfur was established and antifinigal treatment initiated, with adequate outcome of the dermatosis. After this outbreak, the aseptic and hygienic measures of the health care personnel of the ICU were reviewed and corrected. CONCLUSIONS: The simultaneous emergence of this superficial infection by M. furfur suggests fomite participation. This dermatomycosis is an infrequent nosocomial infection in adults, which to our knowledge has not been previously reported.

Dermatosis en pacientes con insuficiencia renal crónica terminal en diálisis peritoneal / Dermatosis in patients with end-stage chronic renal failure on peritoneal dialysis

El tratamiento en pacientes con insuficiencia renal crónica terminal (IRCT) incluye la terapia sustitutiva y el trasplante renal. Tanto en piel como en uñas se observan (..)(AU)

The treatment of patients with final renal disease (FRD) includes dialysis and renal transplant. Skin and nails can show different changes (..) (AU)