Real-Life Utility of Basophil Activation Test in the Diagnosis of Immediate Hypersensitivity Drug Reactions.

INTRODUCTION: The basophil activation test (BAT) is a flow cytometry laboratory technique that assesses the level of activation indicators expressed on the surface of basophils. We conducted a real-life study in a prospective cohort of patients with reported drug hypersensitivity reactions to determine the true relevance of BAT as a diagnostic tool for assessing immediate hypersensitivity reactions to medicines. METHODS: We prospectively assessed individuals with clinical suspicion of immediate hypersensitivity reactions to drugs over a 2-year period. The allergological evaluation was carried out in accordance with European Academy of Allergy and Clinical Immunology (EAACI) guidance. All patients underwent BAT using the activation marker CD63. RESULTS: In total 13 patients with 54 reported immediate drug hypersensitivity reactions to medications were included in this study. Twelve were female (92.3%) and one was male (7.70%). The mean ± SD age of the patients was 47.31 ± 19.94 years. Antibiotics were tested in 35.2% (19/54) of patients, corticosteroids in 24.1% (13/54), iodinated contrast medium in 14.8% (8/54), and NSAIDs in 5.6% (3/54). There was no correlation between the BAT results and the age of patients, gender, type of medication, or time interval between the allergic reaction and BAT procedure. The sensitivity of BAT 5% CD63+ basophils to drugs was 97.6%, specificity was 96% for drug allergies, positive predictive value (PPV) was 94.3%, and negative predictive value (NPV) was 95.2%. CONCLUSIONS: The sensitivity of BAT for drug allergies is limited, but it can nevertheless be very helpful before contemplating provocation testing in cases of life-threatening drug allergies where patients cannot be rechallenged or in cases of medications for which no other tests are available or their results are ambiguous.

Psoriasis immunometabolism: progress on metabolic biomarkers and targeted therapy.

Psoriasis is a common inflammatory disease that affects mainly the skin. However, the moderate to severe forms have been associated with several comorbidities, such as psoriatic arthritis, Crohn's disease, metabolic syndrome and cardiovascular disease. Keratinocytes and T helper cells are the dominant cell types involved in psoriasis development via a complex crosstalk between epithelial cells, peripheral immune cells and immune cells residing in the skin. Immunometabolism has emerged as a potent mechanism elucidating the aetiopathogenesis of psoriasis, offering novel specific targets to diagnose and treat psoriasis early. The present article discusses the metabolic reprogramming of activated T cells, tissue-resident memory T cells and keratinocytes in psoriatic skin, presenting associated metabolic biomarkers and therapeutic targets. In psoriatic phenotype, keratinocytes and activated T cells are glycolysis dependent and are characterized by disruptions in the TCA cycle, the amino acid metabolism and the fatty acid metabolism. Upregulation of the mammalian target of rapamycin (mTOR) results in hyperproliferation and cytokine secretion by immune cells and keratinocytes. Metabolic reprogramming through the inhibition of affected metabolic pathways and the dietary restoration of metabolic imbalances may thus present a potent therapeutic opportunity to achieve long-term management of psoriasis and improved quality of life with minimum adverse effects.

Pruritic annular and vesicular eruption on trunk and extremities.

We report a case of linear IgA bullous dermatosis, a rare autoimmune blistering disorder that usually presents with the abrupt onset of tense bullae. We also emphasize the importance of direct immunofluorescence for the definitive diagnosis.

Hydroxychloroquine-induced erythema multiforme.

Hydroxychloroquine is a commonly used medication and rarely may result in development of erythema multiforme. This potential cutaneous side effect should be highlighted in information given to patients prior to hydroxychloroquine commencement.

Lymphomatoid Papulosis Type A: A Case Report of the "Wait-and-See Strategy" in a 27-Year-Old Male Patient with Extensive Disease.

This is the case of a 27-year-old male patient with a newly diagnosed extensive lymphomatoid papulosis type A involving cosmetically sensitive areas (e.g. face), who refused to be treated with a low dose of methotrexate, as recommended by the published literature. The natural course of the disease was proved to be strikingly satisfying though, with a complete regression of all skin lesions at the 4-week follow-up, including an ulcerated nodule 3 x 3 cm in dimension, which was expected to heal at least in months. We report this case to reconsider weighting the risks and the short-term benefits of methotrexate treatment, even in the case of an extensive disease.

Beware of anal fissures: pemphigus vulgaris of the anal canal.

A case of anal pemphigus vulgaris in a 49-year-old female suffering from pemphigus vulgaris of the oral cavity is reported. The oral manifestations were in remission until she presented with episodes of anal pain and bleeding on defecation, initially mimicking anal fissures. Inspection revealed prominent painful erosions in the anal canal with external hemorrhoids and strands of sloughing skin and maceration in the anal verge. Histology and direct immunofluorescence test were consistent with pemphigus vulgaris. The disease was refractory to treatment and complete remission was only achieved with the combination of rituximab and corticosteroids. Anal involvement seems to be an uncommon or underreported manifestation of pemphigus vulgaris. Gastroenterologists should be aware of this entity, especially in areas with a high incidence of the disease, for appropriate diagnosis and management.

Willingness to pay and quality of life in patients with pruritic skin disorders.

Pruritic dermatosis is a frequent and burdensome disease. The objectives of this study were (1) to assess the willingness to pay (WTP) and the health-related quality of life (HRQoL) in patients with pruritic dermatoses and (2) to compare the results with data on socio-demographic data, and clinical features/symptoms of the patients. One hundred and three patients with pruritic dermatosis had participated in a non-interventional, cross-sectional study. Socio-demographic data, clinical features/symptoms, a health-related quality of life (HRQoL)-based and a dermatology-specific instrument (SF-6D and DLQI, respectively), and two utility indicators such as rating scale (RS) and time-trade-off (TTO) as well as willingness to pay (WTP) were recorded. In our study, there was a significant correlation between DLQI scores and WTP (p < 0.001). Time-trade-off (TTO) was also statistically correlated with SF-6D (p = 0.001). Regression models showed that daily duration and pruritus intensity were associated with lower HRQoL. Furthermore, WTP was the only measure revealing demographic and socio-economic characteristics such as age, education level, family status and income as predicting factors. No significant differences between groups of varying skin diseases were observed. HRQoL and WTP proved to be valid tools to assess the burden of disease in patients with pruritic dermatosis. However, further research with a larger number of patients is needed to validate the present findings.

Mycobacterium avium Auricular Infection in an Apparent Immunocompetent Patient: A Case Report.

INTRODUCTION: Soft tissue infections with Mycobacterium avium complex are more likely to appear in immunocompromised patients. However, they may rarely arise in non-immunosuppressed individuals. AIM: To present the case of an ear infection with Mycobacterium avium in the absence of demonstrable immunosuppression. CASE REPORT: Clinical case description, blood tests, routine histology and tissue cultures. DISCUSSION: A female, apparent immunocompetent patient presented with a 6-month reddish, oedematous and painless lesion with fine scaling in the right ear. Histology showed numerous granulomas, composed of epithelioid histiocytes without central necrosis. Cultures grew Mycobacterium avium. An unusual accidental ear injury was the portal of microbial entry. The patient's lesion fully regressed after a 9-month course of antibiotics. CONCLUSION: Although M. avium infections are rare in immunocompetent patients, the possibility of such infections should be considered even in these subjects, when relevant clinical features and exposure to risk factors are present.

A CD40 and an NCOA5 gene polymorphism confer susceptibility to psoriasis in a Southern European population: a case-control study.

Recent genome-wide association studies of many complex diseases have successfully identified novel susceptibility loci, with many of them shared by multiple disease-associated pathways. The genes CD40 and nuclear receptor coactivator 5 (NCOA5), located in a 400-kb region surrounding CD40, have been reported to be associated with increased risk for rheumatoid arthritis and other autoimmune diseases. We hypothesized that those genes may also have a role in psoriasis (PS), an autoimmune, chronic inflammatory skin disease. In a case-control study, 198 patients with PS and 400 controls were genotyped for 2 single nucleotide polymorphisms (SNPs) of the CD40 and NCOA5 genes located on chromosome 20q.12-q13.12. Here, we demonstrate for the first time the association of both SNPs with susceptibility to PS, thus suggesting a putative key role of both genes in multiple autoimmune diseases. Alleles G and C of the CD40 rs4810485 and NCOA5 rs2903908 SNPs, respectively, were more common in individuals with PS than in controls (p = 0.03, odds ratio [OR] = 1.42, 95% confidence interval [95% CI] 1.05-1.95 and p = 0.000 003, OR = 1.93, 95% CI 1.47-2.55, respectively). The identification of shared genetic susceptibility loci may provide insight into our understanding of the pathophysiology of autoimmune diseases.

The protein tyrosine phosphatase, non-receptor type 22 R620W polymorphism does not confer susceptibility to psoriasis in the genetic homogeneous population of Crete.

Recent whole-genome and candidate-gene association studies in patients with psoriasis (PS) have identified a number of single-nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. Predisposition to PS is known to be affected by genetic variation in human leukocyte antigen-C as well as other non-human leukocyte antigen genes. We recently reported for the first time as a PS-associated SNP the signal transducer and activator of transcription-4 (STAT4) rs7574865 polymorphism, which is also associated with several autoimmune diseases. The aim of this study was to assess whether the functional R620W polymorphism of protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene encoding the lymphoid-specific tyrosine phosphatase, which is known to be associated with various autoimmune diseases, also confers increased risk for PS in the genetic homogeneous population of Crete. A case-control study was performed with 173 PS patients consecutively recruited and 348 healthy controls, all of them from the island of Crete. We found that the mutated T allele of the PTPN22 1858T SNP was more common in control individuals than in patients with PS (odds ratio = 0.39, 95% confidence interval = 0.11-1.04, p = 0.09). No considerable difference was observed in terms of sex, age of onset, or clinical presentation of psoriatic arthritis. Our results provide evidence that the PTPN22 1858T allele is not a susceptibility factor for PS in the Cretan population.

STAT4 gene polymorphism is associated with psoriasis in the genetically homogeneous population of Crete, Greece.

Recent genome-wide association studies (GWAS) of many complex diseases have successfully identified novel susceptibility loci, with many of them being associated with more than one condition. Taking into consideration that different autoimmune diseases may share some common pathogenetic pathways, we hypothesized that STAT4, a susceptibility gene found to be associated with increased risk for systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, Sjögren's syndrome, Wegener's granulomatosis, Crohn's disease, and ulcerative colitis may also have a role in psoriasis. Psoriasis is an autoimmune, chronic inflammatory skin disease. Here we performed a case-control study in the population of island of Crete and demonstrated for the first time the association of a STAT4 single nucleotide polymorphism (SNP) with susceptibility to psoriasis, thus suggesting a putative key role of STAT4 in multiple autoimmune diseases. We found that mutated allele T of the STAT4 rs7574865 SNP, which previously was implicated in the predisposition to many autoimmune diseases, were more common in individuals with psoriasis than in controls (p = 0.045, odds ratio = 1.42, 95% confidence interval 1.01-2.00), thus concluding that the polymorphism examined is associated with the development of psoriasis in our population.

Botulinum toxin type A--treatment of a patient with multiple cutaneous piloleiomyomas.

BACKGROUND: Treatment of multiple cutaneous piloleiomyomas which are rare, frequently painful, benign tumors originating from the arrector pilorum muscle of hair follicles is difficult. OBJECTIVE: To determine the efficiency of botulinum toxin type A (BT-A) treatment for pain relief of cutaneous piloleiomyomas. METHODS: A patient with multiple painful piloleiomyomas was treated with local injections of 200 units of BT-A. RESULTS: There was a rapid and sustained decrease in pain. Treatment was repeated every 3 months for 2 years with the same efficacy. CONCLUSION: BT-A may be a promising new treatment option for multiple painful cutaneous piloleiomyomas.