Identification and management of vulval problems of the postmenopausal woman - Tips and tricks.

Vulval irritation and discomfort can be a common presentation to both primary and secondary care. These symptoms can become increasingly prevalent due to physiological changes, which occur to the female genitalia following menopausal transition or due to inflammatory conditions. The correct diagnosis and management can have a huge impact on the patients' quality of life. However, due to the nature of the symptoms, there can be delayed presentation to healthcare professionals. This article gives an overview of the most common benign vulval conditions in the post-menopausal woman, their clinical features and the diagnosis and initial management.

Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study.

BACKGROUND: Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high-affinity receptor (FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU. METHODS: This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti-FcεRI and IgG anti-IgE; IgG-anti-thyroperoxidase (IgG anti-TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA). RESULTS: Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti-FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non-aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti-TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively. CONCLUSIONS: aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.

SLURP-1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene.

BACKGROUND: Mal de Meleda (MDM) is a rare inherited autosomal recessive genodermatosis characterized by palmoplantar keratoderma (PPK) with transgrediens and caused by mutations in the SLURP1 gene. Uncommonly, cutaneous tumors have been found at PPK sites in MDM patients. OBJECTIVE: To study a Middle Eastern family with MDM with both PPK and skin tumors. METHODS: We studied a Middle Eastern (Palestinian) family with clinical features of MDM and cutaneous tumors. Histopathological analysis was performed on biopsies from skin lesions found in the affected individuals. Direct sequencing of SLURP1 was performed in MDM affected members. In silico analysis of publicly available datasets was used to survey SLURP1 mRNA levels in normal and malignant tissues. Statistical analysis was performed in the R statistical language. RESULTS: Affected members from the Middle Eastern family displayed severe forms of PPK consistent with MDM. Histopathological analysis of the skin lesions revealed that the examined affected members exhibited skin squamous cell carcinomas (SCCs) and melanoma. Sequence analysis revealed homozygous SLURP1 mutations (c.82delT) in the affected members. Following analysis of various publicly available expression datasets, SLURP1 mRNA levels were found to be markedly elevated in tissues of epithelial lineage, relative to tissues of other lineages, and significantly suppressed in malignant tumors of epithelial lineage relative to normal or their premalignant counterparts. There was significant decrease in SLURP-1 expression in melanomas versus melanocytic nevi as well as a highly significant decrease in SLURP-1 expression in metastatic melanomas as compared to primary melanoma. CONCLUSION: Our study underscores cases of Middle Eastern MDM with SLURP1 mutations and skin malignancies at PPK sites. Our findings also highlight a plausible epithelial lineage-specific tumor suppressor role for the SLURP1 gene, as well as a role in the development and metastasis of melanoma and thus a potential molecular signature for melanoma.

Pityriasis rubra pilaris: clinicopathological study of 32 cases from Lebanon.

BACKGROUND: Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous disorder of unknown etiology. Studies on this condition from our region are lacking. METHODS: To describe the clinical and histopathological findings as well as response to treatment of all patients diagnosed with PRP at the American University of Beirut Medical Center between 1995 and 2010 and compare our findings with those published in the literature. RESULTS: Pityriasis rubra pilaris was diagnosed in 32 patients (16 males, 16 females). Age of onset ranged between 2.5 and 70 years. The majority of patients (n=15) were classified as type I (47%) followed by type III (n=9, 28%) and type IV (n=6, 19%). Based on treatment responses, retinoids appear to be very effective in our population as all patients treated with isotretinoin or acitretin had excellent response. In addition to checkerboard alternating orthokeratosis/parakeratosis, which was observed in 31 cases, interesting features, including the presence of follicular plugging in all 21 cases in which follicles were available for examination, eosinophils in 12 cases, and focal acantholysis in three cases were observed. CONCLUSIONS: Features of patients with PRP in our study are generally comparable to those published in the literature, with minor differences. Microscopically follicular plugging, in addition to checkerboard alternating orthokeratosis/parakeratosis, may serve as clues to PRP diagnosis. The presence of eosinophils and focal acantholysis, observed in a few cases, should not exclude PRP diagnosis.

Update and insights into treatment options for chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is defined as itchy weals, angio-oedema, or both, arising spontaneously without external physical stimuli. Symptoms of the disease continue to develop for more than 6 weeks. It carries a high socioeconomic burden with considerable health care costs. Second generation H1-antihistamines are the mainstay of urticaria treatment and are the only licensed option. However, many patients are resistant to H1-antihistamine therapy. Omalizumab has proven to be an effective therapeutic option in patients with recalcitrant chronic urticaria. Ciclosporin appears to be more beneficial in patients with functional histamine releasing autoantibodies as a cause of their disease. This review article will highlight the major therapeutic options available today for the management of CSU knowing that good quality evidence for efficacy of many agents is scarce except for H1-antihistamines and omalizumab.

Childhood urticaria.

PURPOSE OF REVIEW: The present article reviews childhood urticaria. It provides an update on the current understanding of its pathophysiology and highlights the current practice in the management of this condition. RECENT FINDINGS: Progress has been made in understanding the pathophysiology of urticaria with the elucidation of an autoimmune basis in a significant proportion of children with chronic spontaneous urticaria. H1-antihistamines remain the mainstay of therapy, but there is increasing awareness on the risks of sedating first-generation antihistamines. Omalizumab is increasingly being used off-license in the most refractory cases. SUMMARY: Urticaria is a common disease that affects children and adults. However, paediatric urticaria has specific features and remains poorly understood. Acute spontaneous urticaria is the most common clinical presentation in childhood. It is caused by viral infection in most cases with an identifiable trigger. By contrast, chronic spontaneous urticaria in children may be autoimmune, but more studies are needed to understand the clinical significance of functional autoantibodies in this subgroup of patients. Investigations should always be guided by history. Treatment remains largely symptomatic. H1-antihistamines are the mainstay of therapy but are insufficient to control symptoms in all patients. There is an urgent need for more efficacious therapies.