An observational analysis of low-dose thalidomide in recalcitrant prurigo nodularis.

Thalidomide has been used as an effective treatment for prurigo nodularis (PN) with a median dose of 200 mg, but the risk of peripheral neuropathy precludes long-term use. We analysed the efficacy of low-dose thalidomide (< 100 mg) in 17 patients with recalcitrant PN. Patients were initiated on thalidomide 50 mg on alternate days, and the dose was increased (doubled) in a stepwise manner, if needed, until a ≥ 50% reduction in score (partial response; PR) on a visual analogue scale (VAS) was achieved. Thalidomide then was continued at the same dose for 4 weeks to achieve ≥ 90% decrease in VAS score; if this was not achieved, the dose was increased to a maximum of 100 mg and continued until complete resolution of lesions (complete response; CR). Four patients discontinued thalidomide due to adverse effects. Four patients achieved PR, while 9 patients (n = 2 with 50 mg, n = 7 with 100 mg) achieved CR. No patient developed neuropathy. In addition, complete responders achieved an earlier ≥ 50% reduction in VAS score. Two patients relapsed after 12 months but responded to thalidomide 50 mg.

An observational study of the efficacy of azithromycin in erythema annulare centrifugum.

Erythema annulare centrifugum (EAC) is a form of figurate erythema consequent to a cutaneous hypersensitivity reaction to an underlying agent. In the present study, we aimed to assess the role of oral azithromycin in cases of idiopathic EAC. We performed an open trial of azithromycin in 10 patients with idiopathic EAC. Histopathological examination of biopsies was performed to exclude any alternative diagnosis and to assess the depth of the infiltrate. Patients were administered oral azithromycin 250 mg once daily until clinical resolution of the disease, and followed up regularly to monitor for possible relapse. Histopathological examination of the 10 biopsies revealed superficial pattern in 3, deep pattern in 2 and mixed pattern in the remaining 5. Of the 10 patients, 8 responded to azithromycin 250 mg, with no relapse during follow-up. Oral azithromycin might be a promising therapy in cases of idiopathic EAC. Cases with a superficial pattern respond earlier than cases with a deep pattern.

Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic).

Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major cause of hearing impairment (HI). More than 300 allelic variants have been identified in the GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide. Until now, the spectrum and frequency of the pathogenic variants in exon 1, exon 2 and the flanking intronic regions of the GJB2 gene have not been described thoroughly in the Sakha Republic (Yakutia), which is located in a subarctic region in Russia. The complete sequencing of the non-coding and coding regions of the GJB2 gene was performed in 393 patients with HI (Yakuts-296, Russians-51, mixed and other ethnicities-46) and in 187 normal hearing individuals of Yakut (n = 107) and Russian (n = 80) populations. In the total sample (n = 580), we revealed 12 allelic variants of the GJB2 gene, 8 of which were recessive pathogenic variants. Ten genotypes with biallelic recessive pathogenic variants in the GJB2 gene (in a homozygous or a compound heterozygous state) were found in 192 out of 393 patients (48.85%). We found that the most frequent GJB2 pathogenic variant in the Yakut patients was c.-23+1G>A (51.82%) and that the second most frequent was c.109G>A (2.37%), followed by c.35delG (1.64%). Pathogenic variants с.35delG (22.34%), c.-23+1G>A (5.31%), and c.313_326del14 (2.12%) were found to be the most frequent among the Russian patients. The carrier frequencies of the c.-23+1G>A and с.109G>A pathogenic variants in the Yakut control group were 10.20% and 2.80%, respectively. The carrier frequencies of с.35delG and c.101T>C were identical (2.5%) in the Russian control group. We found that the contribution of the GJB2 gene pathogenic variants in HI in the population of the Sakha Republic (48.85%) was the highest among all of the previously studied regions of Asia. We suggest that extensive accumulation of the c.-23+1G>A pathogenic variant in the indigenous Yakut population (92.20% of all mutant chromosomes in patients) and an extremely high (10.20%) carrier frequency in the control group may indicate a possible selective advantage for the c.-23+1G>A carriers living in subarctic climate.

Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = -0.81); most patients with low-medium (39-55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39-55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow's index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.

Dermatopathia Pigmentosa Reticularis with Salzmann's nodular degeneration of cornea: A rare association.

BACKGROUND: Dermatopathia pigmentosa reticularis (DPR) is a very rare autosomal dominant disorder with the diagnostic triad of generalized reticulate hyperpigmentation, noncicatricial alopecia and onychodystrophy. OBJECTIVE: To describe the occurrence of Salzmann's nodular degeneration of cornea with moderate dry eye in a patient with Dermatopathia pigmentosa reticularis. CASE: We present an 11 year old young Indian girl with DPR who had Salzmann's nodular degeneration of cornea with moderate dry eye. She was put on symptomatic treatment and counseled regarding the course of disease, familial nature and avoidance of exposure to sun. CONCLUSION: In a patient of Salzmann`s nodular degeneration with generalized reticulate hyperpigmentation, noncicatricial alopecia and onychodystrophy the diagnosis of DPR must be kept in mind. A multidisciplinary approach is required for the management of such cases.

Asymptomatic reproductive tract infections/sexually transmitted infections among HIV positive women.

This study aims to highlight the importance of screening all HIV positive women for various reproductive tract infections/sexually transmitted infections (RTIs/STIs) irrespective of symptoms and to determine its occurrence in asymptomatic HIV positive women. Relevant specimens were collected for diagnosis of various RTIs/STIs. STIs were diagnosed in nearly one-third of the HIV positive asymptomatic patients which is quite high. The national strategy for STIs/RTIs control misses out large number of asymptomatic RTIs/STIs in HIV positive women which is responsible for silently transmitting these infections in the community. So this strategy should be modified to include screening of all HIV positives women irrespective of symptoms of STIs/RTIs.

Rising trend of antimicrobial resistance among Neisseria gonorrhoeae isolates and the emergence of N. gonorrhoeae isolate with decreased susceptibility to ceftriaxone.

CONTEXT: Gonorrhoea is one of the most common sexually transmitted infections (STI) in developing countries and is a global health problem. AIMS: To analyze the trend of antimicrobial susceptibility of Neisseria gonorrhoeae isolates over the years, in a tertiary care hospital of North India. SETTINGS AND DESIGN: The study population comprised males with urethritis and females with endocervicitis attending STI clinic of our hospital. MATERIALS AND METHODS: In our STI laboratory, all gonococcal isolates are subjected to antimicrobial susceptibility testing by disc diffusion method as per CLSI guidelines. ß-Lactamase production is determined by chromogenic cephalosporin test. Minimum Inhibitory Concentration (MIC) for ceftriaxone is determined by E-test. STATISTICAL ANALYSIS USED: Data were expressed as percentages. The differences in percentages were tested for statistical significance by using χ2 test and P values were determined. RESULTS: The percentage of penicillinase producing N. gonorrhoeae (PPNG) increased from 8% in 1995-96 to 20% in 2004-05 and 88% in 2011-2013. Quinolone-resistant N. gonorrhoeae (QRNG) showed a significant increase from 12% in 1995-96 to 98.3% in 2004-05, while 84% isolates were found to be QRNG by 2011-2013. In January 2013 we detected our first gonococcal isolate with decreased susceptibility to third-generation cephalosporins; Ceftriaxone, Cefixime and Cefpodoxime (MIC for ceftriaxone = 0.19 µg/ml). CONCLUSIONS: The results of our study highlighted an alarming increase in the percentage of PPNG and QRNG strains over the years. Emergence of N. gonorrhoeae isolates with decreased susceptibility to third-generation cephalosporins is a cause of concern and thus emphasises the importance of antimicrobial susceptibility testing.

Bioethical issues of preventing hereditary diseases with late onset in the Sakha Republic (Yakutia).

BACKGROUND: Prenatal diagnosis of congenital and hereditary diseases is a priority for the development of medical technologies in Russia. However, there are not many published research results on bioethical issues of prenatal DNA testing. OBJECTIVE: The main goal of the article is to describe some of the bioethical aspects of prenatal DNA diagnosis of hereditary diseases with late onset in genetic counselling practice in the Sakha Republic (Yakutia) - a far north-eastern region of Russia. METHODS: The methods used in the research are genetic counselling, invasive chorionic villus biopsy procedures, molecular diagnosis, social and demographic characteristics of patients. RESULTS: In 10 years, 48 (76%) pregnant women from families tainted with hereditary spinocerebellar ataxia type 1 and 15 pregnant women from families with myotonic dystrophy have applied for medical and genetic counselling in order to undergo prenatal DNA testing. The average number of applications is 7-8 per year. There are differences in prenatal genetic counselling approaches. CONCLUSION: It is necessary to develop differentiated ethical approaches depending on the mode of inheritance, age of manifestation, and clinical polymorphism of hereditary disease.

'Congenital follicular melanocytic naevi': a more appropriate term for spotted grouped pigmented naevi.

We report two patients with an uncommon form of pigmented naevus consisting of grouped follicular papules. A biopsy taken from the lesions showed multiple naevus cells, predominantly around the hair follicles, with sparing of the eccrine glands. The clinicohistopathological term given for this condition is 'spotted grouped pigmented naevi type I', and has rarely been reported. We discuss the unusual morphology and differential diagnosis of this condition, and suggest that the term 'congenital follicular melanocytic naevi' is more appropriate for this presentation.