HLA-DR expression on keratinocytes is a common feature of diseased skin

Biopsy specimens from 185 patients with 52 different skin disorders were investigated by indirect immunofluorescence staining for the presence of HLA-DR bearing keratinocytes and their association with an underlying inflammatory infiltrate and in particular with activated (HLA-DR-positive, Leu-4-positive) T lymphocytes. HLA-DR expression on keratinocytes was demonstrated in 38 dermatoses, including lymphocytic vasculitis, lupus erythematosus, morphea, vitiligo, lichen planus, cutaneous T-cell lymphoma, various infectious dermatoses, allergic contact dermatitis, granulomatous dermatoses, Sweet's syndrome, lichen sclerosus and erythema nodosum. In 27 of these this had not previously been reported. Occurrence of HLA-DR on keratinocytes was invariably linked to the presence of a lymphocytic infiltrate containing numerous activated T-cells (Leu-4 +, HLA-DR +) whereas such infiltrates were not accompanied by HLA-DR expression on keratinocytes in all the dermatoses investigated, as in pseudolymphoma and erythema anulare centrifugum. However, HLA-DR positive keratinocytes were consistently absent in skin disorders lacking any significant lymphocytic infiltration (e.g. leukocytoclastic vasculitis, bullous autoimmune dermatoses, genodermatoses and mastocytosis). Although it has been suggested that HLA-DR-positive keratinocytes are involved in various immune responses of the skin, their exact functional significance is, as yet, unknown.     

Helicobacter pylori management in ASEAN: The Bangkok consensus report

Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa‐associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow‐up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.     

Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome

Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high‐level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K‐means clustering approach based on several midline structural measures‐of‐interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy‐looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left–right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior‐posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis‐proneness risk found in 22q11DS. Hum Brain Mapp 39:232–248, 2018. © 2017 Wiley Periodicals, Inc.     

Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review

Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in APRT (OMIM #102600). APRT deficiency results in increased urinary excretion of 2,8-dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11-year-old brother and his 14-year-old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in APRT with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere-like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister's diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the APRT gene in a pair of siblings with greater phenotypic severity in the male.

     

Facial psoriasis in the etiology of prolonged erythema following medium-depth chemical peels for severe photodamage

Background

Chemical peeling is the controlled wounding of the epidermis and dermis for skin rejuvenation, involving the application of ablative agents to induce keratolysis and regeneration of damaged cell layers. Prolonged erythema is one complication of this procedure. We report the prevalence and probable etiology of prolonged facial erythema in a cohort of patients treated with medium-depth chemical peels.

Materials and Methods

A retrospective audit was conducted of all medium-depth facial chemical peels performed at two major teaching hospitals. All patients had severe facial photodamage affecting at least 75% surface area of the face. The occurrence of prolonged erythema following this peel was then identified and analyzed.

Results

Of our treatment cohort (n = 82, 51 women, 31 men) with 60 years mean (61.3 years for women, 56.7 years for men), 10 patients (12%; eight women, two men) experienced prolonged erythema beyond a month of treatment. Facial psoriasis was not apparent at the time of chemical peel but manifested as prolonged erythema beyond the expected timeframe following the procedure.

Conclusion

When patients experience prolonged erythema beyond a month of treatment and fail to respond to standard treatments, clinicians should examine carefully for extra-facial psoriasis prior to this procedure, and also consider facial psoriasis a possible cause of prolonged post-peel erythema.