Symmetrical drug-related intertriginous and flexural exanthema/baboon syndrome induced by traditional Chinese medicine.

BACKGROUND: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) refers to an uncommon cutaneous adverse reaction that symmetrically involves the buttock and intertriginous areas after systemic exposure to the offending drug and is previously known as baboon syndrome. SDRIFE related with traditional Chinese medicine (TCM) has not been reported. OBJECTIVE: We presented a case of SDRIFE /baboon syndrome induced by TCM, Xi-Huang capsule. METHODS: A 57-years-old man presented with macular erythematous rash mainly on his intergluteal, inguinal, axillary, popliteal regions for a duration of 5 days. The lesions appeared a day after an oral Chinese patent medicine Xi-Huang capsule for arthralgia. Drug eruption was diagnosed. The rash disappeared completely within a week with immediate discontinuation of Xi-Huang capsule and a short term of systemic therapy with glucocorticosteroids. Patch testing was performed on the patient 1 month after complete resolution. He was patch tested with Xi-Huang capsule (5% and 10% in petroleum) using Finn Chambers on Scanpor tape and T.R.U.E. test system. Five heathy volunteers were also patch tested with the same Xi-Huang capsule. RESULTS: Patch testing to 20 common contact allergens including nickel and fragrance were negative. TCM patch test was positive. No positive results were found in five volunteers. Months later, the patient relapsed after an oral herbal Chinese medicine challenge for arthralgia. To avoid the rash recurrence, he stopped taking any Chinese herbal medicine and had complete resolution of disease. CONCLUSION: The Chinese patent drugs for external and oral have unique advantages and have been widely used in many diseases. It is important that dermatologists monitor for clinically significant manifestations of TCM, such as baboon syndrome. Patch testing could help make a definitive diagnosis.

[Sebotropic drug eruption after ingestion of bee pollen]. / Éruption induite à tropisme sébacé après consommation de pollen d'abeille.

INTRODUCTION: The medical literature contains five cases of exanthema with sebaceous tropism induced by consumption of kava-kava extract filed under the name of sebotropic drug reaction. Herein we report a new case following consumption of bee pollen. PATIENTS AND METHODS: A 37-year-old man consulted for erythemato-papular and fixed plaques of the face, upper trunk and shoulders present for 3 days. Standard blood tests were normal except for neutrophil leukocytosis at 9.8 G/l and eosinophilia at 1.4 G/l. Cutaneous biopsy of a facial plaque revealed folliculocentric lesions with necrosis of sebocytes in the sebaceous gland, associated with an eosinophil-rich infiltrate. The patient had begun consuming bee-pollen granules 3 weeks before the onset of symptoms. The rash regressed within 3 weeks of cessation of pollen consumption. Patch tests (ICDRG battery, propolis 1% Vaseline dilution and bee pollen provided by the patient, both pure and in a 30% dilution in Vaseline) were negative at 48 and 72h. DISCUSSION: The clinical-pathological correlation was consistent with a diagnosis of sebotropic drug reaction induced by the consumption of bee pollen. The diagnosis was based on papular exanthema of the seborrheic zones occurring 2 to 3 weeks after initial intake of the offending substance, with histological evidence of inflammatory necrosis of the sebaceous glands. CONCLUSION: We report what is to our knowledge the first case of sebotropic drug reaction following ingestion of bee pollen.

Perplexing Rash: Challenges to Diagnosis and Management of Mycosis Fungoides.

Mycosis fungoides is the most ubiquitous form of cutaneous T-cell lymphoma. Diagnosis is arduous, as early phases often resemble common inflammatory dermatoses. The principal histologic features of MF include medium to large-sized cerebriform mononuclear cells in single or small clusters in the epidermis. Treatment modalities are prodigious and relapses are common. The authors present a case of a 69-year-old man with mycosis fungoides, followed by a review of diagnostic modalities and phototherapeutic interventions for patients with this condition. According to literature reports, monochromatic excimer light therapy is the most advantageous and well-tolerated phototherapy modality for patients with early patch stage mycosis fungoides.

Abrupt generalized pustules in patients with rheumatoid arthritis and interstitial lung disease.

We report a case of a 30-year-old Chinese woman with rheumatoid arthritis and interstitial lung disease who abruptly developed generalized pustules and a high fever for 10 days. She had been taking oral prednisone, iguratimod and total glucosides of peony regularly for 5 months prior. In addition, she had taken metronidazole for 3 days 20 days prior which she had used before with no adverse reaction. She had no history of similar lesions and psoriasis. A biopsy of a pustule on the back showed spongiform pustule of Kogoj. She was suspected of having generalized pustular psoriasis or acute generalized exanthematous pustulosis. Finally, she was diagnosed with generalized pustular psoriasis (von Zumbusch type) considering the characteristics and clinical course of the rash. In addition to the above three drugs, systemic cyclosporin (5 mg/kg per day) was applied, and the lesions and fever resolved within the proceeding 2 months.

Insect-bite-like reaction in patients with chronic lymphocytic leukemia: a study from the Israeli Chronic Lymphocytic Leukemia Study Group.

An insect-bite-like reaction is known to occur in patients with chronic lymphocytic leukemia (CLL). Most of the literature, however, consists of isolated case reports or small case series. The aim of this retrospective study was to review the national experience with insect-bite-like reaction in a large group of patients with CLL. The study cohort of patients with these skin reactions consisted of 48 patients (25 males, 23 females) of mean age 64.8 yr (range 33-89) at skin eruption. Data on clinical, histologic, immunophenotypic, and cytogenetic characteristics, treatment, and outcome were collected from the medical files. Mean time between diagnosis of CLL and appearance of the skin lesions was 3.1 yr (range -4 to 14 yr). The eruption was not related to disease activity or the course of the hematological disease. The eruption preceded the diagnosis of CLL in 10 patients (by 0-4 yr); and followed the diagnosis in 36; in 11 patients, it occurred during therapy for CLL and in nine after therapy. Mean duration of the skin findings was 21.5 months (range 0.3-132). The eruption usually presented in summer, although it occurred also at other times of the year, and predominantly affected the upper and lower limbs, although it also appeared on unexposed areas. Treatment included local ointments, antihistaminics, oral steroids, antibiotics, phototherapy, and dapsone with varying responses. Insect-bite-like reactions is a relatively common and disturbing skin reaction in CLL patients, it may be related to the immune dysregulation accompanying CLL and further exacerbated by external factors, including actual insect bites, chemoimmunotherapy, and pyogenic infection.

Constituents in kava extracts potentially involved in hepatotoxicity: a review.

Aqueous kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kava constituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. Reactive metabolites of kava lactones have been identified in vitro as glutathione (GSH) conjugates and in vivo as mercapturates excreted in urine. Addition of GSH to kava extracts has been shown to reduce cytotoxicity in vitro, which suggests the presence of inherently reactive constituents. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries.

Benefit of erlotinib in patients with non-small-cell lung cancer is related to smoking status, gender, skin rash and radiological response but not to histology and treatment line.

BACKGROUND: Erlotinib is a standard of treatment for metastatic non-small-cell lung cancer after failure of initial therapy. Patient selection based on clinical factors is under discussion. METHODS: We analyzed the outcome in relation to clinical factors of 121 consecutive Caucasian patients treated with erlotinib in a routine clinical setting in a comprehensive cancer center and 2 regional oncology centers. RESULTS: For patients with erlotinib treatment at the 1st/2nd/3rd/> or = 4th line, progression-free survival (PFS) was 4.5/3.5/2.5/3.0 months, and overall survival (OS) was 8.0/8.5/7.8/6.5 months. Patients with adenocarcinoma had an improved PFS, but a similar OS. Never-smokers had longer PFS (7 months) and OS (13 months) than smokers and ex-smokers. Male patients had a slightly longer survival than female patients (PFS 3.0 vs. 2.5 months, OS 8.5 vs. 7.0 months). After adjustment for smoking and histology, the gender difference in OS was significant (adjusted hazard ratio 0.57). Patients with clinically relevant skin toxicity (grade 2, 3) had a significantly prolonged PFS and OS. Patients with partial response on 1st radiological evaluation had a significantly prolonged PFS and OS. CONCLUSION: Among clinical factors, never-smoking status and male gender predicted a prolonged survival. During treatment, skin toxicity and radiological response were related to better survival.

Lest we forget Hansen's disease (leprosy): an unusual presentation with an acute onset of inflammatory polyarthritis and the rheumatology experience.

Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.

Malnutrition and a rash: think zinc.

Endemic zinc deficiency is recognised to be a common and serious problem in developing countries. However, it may be seen in routine practice in the UK, and can be easily overlooked. Malnutrition from any cause in conjunction with an undiagnosed cutaneous problem should alert the clinician to the diagnosis. Investigations may be unreliable, and if in doubt, a therapeutic trial of zinc supplementation is indicated. We present three cases of malnourished patients, in whom zinc deficiency was diagnosed after the development of cutaneous features. The malnutrition resulted from alcoholism in two cases and anorexia nervosa in the third. The heterogeneity of underlying causes of zinc deficiency is discussed, along with its effects, treatment and zinc homeostasis.

Acute generalised exanthematous pustulosis induced by the herbal remedy Ginkgo biloba.

Acute generalised exanthematous pustulosis (AGEP) is a clinical reaction pattern that is induced, in over 90% of cases, by systemic drugs (most frequently antibacterial drugs). This is the first reported case of AGEP caused by the herbal remedy Ginkgo biloba.

Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer.

BACKGROUND: Only 15% of patients with non-small cell lung cancer (NSCLC) treated with oral epidermal growth factor tyrosine kinase inhibitor gefitinib, as a second-line therapy have objective responses. Fifty percent will have improvement of lung cancer related symptoms. It will be critical to identify patients who will benefit clinically from this therapy even when there is no objective response seen on imaging studies. We have performed a retrospective analysis of 76 patients who received gefitinib as a therapy for previously treated metastatic NSCLC at the University of Minnesota Comprehensive Cancer Center in order to describe characteristics of patients who will likely derive benefits from gefitinib therapy. METHODS: All patients treated with gefitinib therapy at the University of Minnesota from September 2001 to January 2004 were entered into the study. The Log-rank Test and Cox proportional hazards regression were used to assess the effect of the number of previous therapy lines, histology subtype, performance status, gender, stage of disease at initial diagnosis, and presence of skin rash on time to disease progression and overall survival (OS). Fisher's Exact Test and multiple logistic regressions were used to assess the effect of these covariates on disease response. RESULTS: Seventy-six patients entered the study, with a median age of 60 years (range 37-82). There were 37 female and 39 male patients; 47 patients had adenocarcinoma, 22 had squamous and 7 had other NSCLC histologies. Six patients had no prior therapy, 23 had one, 32 had two, 8 had three, and 7 had four prior therapies for lung cancer. Fifty-six were current smokers. Median time to disease progression was 3 months (95% CI: 3.0, 6.0). There was no difference in time to disease progression whether patients had one or more prior therapies. Patients with brain metastases (26 patients) benefited from gefitinib therapy at least equally well as those without brain metastatic disease. Patients with adenocarcinoma histology with bronchoalveolar features had superior median time to progression versus other lung cancer histology (14 months versus 3 months, p=0.076), which translated into survival advantage in this group >24 months (95% CI: 0.76, 24+) versus 6.6 months (p=0.0096). Patients with EGFR positive tumors had median survival of 10.2 months (95% CI: 1.45, 16.94) versus 3.7 months (95% CI: 2.66, 4.74) with EGFR negative tumors. Patients who developed any degree of skin rash had prolonged time to disease progression with median of 6 months (95% CI: 2.56, 15.5) versus patients without skin rash median 3 months (95% CI: 1.43, 2.83) (p=0.023). This last factor was the best predictor of improved time to disease progression in multiple regression analysis (p=0.0405). CONCLUSION: A subgroup of patients with NSCLC will benefit from gefitinib therapy. Objective responses will likely be seen in half the patients with mutation of internal domain of EGFR; however, a larger group of patients will also enjoy prolonged disease stabilization and clinical benefit. We suggest that adenocarcinoma with bronchoalveolar features and the presence of skin rash may be used as predictors of gefitinib benefit.

Grover's disease: 34 years on.

Grover's disease is an entity reported worldwide and recognized as a common disease since Grover first described it in 1970. Its cause remains obscure, but hospitalized, febrile and sun-damaged patients are particularly prone. It is frequently associated with some other skin diseases, including eczemas, psoriasis and solar keratoses. Acantholysis is the universal histological finding in all the varying clinical presentations. Treatment in the past has been ad hoc, but topical therapy, acitretin and phototherapy can suppress symptoms.

Characterization of a potential animal model of an idiosyncratic drug reaction: nevirapine-induced skin rash in the rat.

Idiosyncratic drug reactions are difficult to study in humans due to their unpredictability. Unfortunately, this characteristic also hinders the development of animal models needed for mechanistic studies. Nevirapine, used to treat human immunodeficiency virus (HIV) infections, results in a severe idiosyncratic skin rash in some patients. We found that nevirapine can also cause a significant rash in some strains of rats. At a dose of 150 mg/kg/day, the incidence in female Sprague-Dawley rats was 6/28 (21%), in female Brown Norway rats 32/32 (100%), and in female Lewis rats 0/6 (0%) while no male Sprague-Dawley or Brown Norway rats developed a rash. Female SJL mice 0/7 also did not develop nevirapine-induced skin lesions. The first sign of a reaction in Brown Norway rats was red ears at days 7-10 followed by a rash with scabbing mainly on the back; this was a shorter time to onset than in Sprague-Dawley rats. Light microscopy of the skin revealed a primarily mononuclear inflammatory infiltrate and lesions typical of self-trauma. Immunohistochemistry results suggest that the infiltrate was composed of CD4 and CD8 T cells as well as macrophages. A lower dose of either 40 or 75 mg/kg/day did not lead to a rash and, in fact, 2 weeks of the lower doses induced tolerance to the 150 mg/kg/day dose in female Brown Norway rats. A dose of 100 mg/kg/day resulted in rash in 2/4 (50%) of female Brown Norway rats. Rechallenge of Brown Norway rats that had been allowed to recuperate after a nevirapine-induced rash led to red ears in less than 24 h followed by hair loss and occasional skin lesions. Although the skin rash was less evident on rechallenge, microscopically, the cellular infiltrate was more prominent, especially surrounding the hair follicles. Moreover, there were lesions of interface dermatitis with apoptosis and satellitosis, indicative of a cell-mediated immune attack on the epidermis. While systemic signs of illness did not accompany the rash on primary exposure, on rechallenge, the animals appeared generally unwell and this forced sacrifice after 2 weeks or less of treatment. Importantly, splenocytes isolated from rechallenged animals were able to transfer susceptibility to nevirapine-induced skin rash to naïve female Brown Norway recipients, which was illustrated by a faster time to onset of rash in the recipients. The characteristics of this adverse reaction are similar to that seen in humans; that is, it is idiosyncratic in that it only occurs in some strains of animals, is delayed in onset, is more common in females, is dose-dependent, and appears to be immune-mediated. Therefore, it may represent a good animal model for the study of idiosyncratic drug reactions.

Acute generalized exanthematous pustulosis induced by chromium picolinate.

A case of acute generalized exanthematous pustulosis (AGEP) due to chromium picolinate is described. This supplemental form of chromium has received a great deal of interest recently because of its possible beneficial effects on both muscle strength and body composition. There have been no previous reports to our knowledge of adverse cutaneous reactions to this agent. Various aspects of AGEP are reviewed.