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Background: ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR. Objectives: To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients. Methods: Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0‐II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment. Results: At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) −9.3 versus −4 points (p = <.00) in the patient's neuropathy total symptom score 6 (NTSS‐6) questionnaire, (2) −2.5 versus +2.8 points (p = <.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus −0.6 (p =.01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis‐treated patients, whereas it rose across all the biopsies in the control group. At the 4‐year follow‐up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of −3.0 vs. −9.3 fibers/mm) and the distal leg (mean difference [MD] −4.9 vs. −8.6 fibers/mm). ADI in tafamidis‐treated patients was also lower in the distal thigh (10 vs. 30 amyloid/mm2) and the distal leg (23 vs. 40 amyloid/mm2) compared to control patients. Plasma tafamidis concentrations were higher in patients with IENFD improvement and in patients with reduced amyloid deposition. Patients without amyloid deposition in the distal leg at baseline displayed delayed disease progression at 4 years. Conclusions: Cutaneous IENFD and amyloid deposition assessments in the skin of the distal thigh and distal leg are valuable biomarkers for early diagnosis of ATTR amyloidosis and for measuring the progression of small nerve fiber neuropathy. Early treatment with tafamidis slows the clinical progression of the disease, skin denervation, and amyloid deposition in the skin. Higher plasma concentrations of tafamidis are associated with better disease outcomes, suggesting that increasing the drug dose could achieve better plasma concentrations and response rates. This study describes the longest small nerve fiber neuropathy therapeutic trial with tafamidis and is the first to report small fiber symptoms, function, and structural assessments as outcomes. [ABSTRACT FROM AUTHOR]

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = −0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker. [ABSTRACT FROM AUTHOR]

Background: Bovine besnoitiosis (elephant skin disease) caused by Besnoitia besnoiti is a costly endemic disease in the Middle East, Asia, and tropical and subtropical Africa and is also emerging as a significant problem in Europe. This study is aimed at determining the prevalence of B. besnoiti in blood and skin biopsies of cattle as well as evaluating the risk factors associated with the infection among cattle in Mosul, Iraq. Methods and results: To achieve this aim, four hundred and sixty apparently healthy cattle of different breeds, ages, and sexes were sampled from seven different locations in Mosul, Iraq. Blood and skin biopsies were carefully collected from each cattle, and these samples were subjected to molecular analysis. The detection of B. besnoiti was molecularly confirmed by the presence of 231 bp of ITS-1 in the rDNA gene of the protozoan. Besnoitia besnoiti DNA was present in 74 (16.09%; 95% CI = 13.01–19.72) and 49 (10.65%; 95% CI = 8.15–13.80) of the blood and skin biopsies, respectively, that were analyzed. Age, breed, and sex were significantly (p < 0.05) associated with the occurrence of B. besnoiti among cattle in the study area. Conclusions: Findings from this study will serve as baseline data in the epidemiology, prevention, and control of the protozoan among cattle in Iraq. [ABSTRACT FROM AUTHOR]

Objectives Adult T-cell leukemia/lymphoma (ATLL) is a rare aggressive T-cell leukemia/lymphoma associated with human T lymphotropic virus type 1 infection. The patients might present with skin rash before, at, or after the diagnosis. The dermatopathologic finding might be diagnostically very challenging. Methods We retrospectively identified 110 patients with ATLL at a single institution in a 19-year period, with 19 patients having skin biopsies. Clinical, dermatopathologic, immunophenotypic, and molecular findings were studied. Results The cohort included 13 skin-first (5 acute, 5 lymphomatous, 2 chronic, 1 smoldering), 6 skin-second (4 acute, 1 lymphomatous, 1 smoldering), and 91 patients without skin biopsy. Some nonphotoprotected areas of body such as the forearm and lower lip were also seen. Skin manifestations included papular (5), erythroderma (1), nodulotumoral (3), plaques (1), patches (1), and a combination of skin rashes (2). Histopathologic findings included large pleomorphic cells, angiocentrism, epidermal infiltration with large Pautrier-like microabscesses, and folliculotropism. Fifteen (78.9%) cases showed CD4+/CD7–/CD25+. Next-generation sequencing study was conducted on 5 patients using either blood or bone marrow samples, revealing multiple genetic mutations across multiple signaling pathways. Conclusions Pleomorphic large, atypical cells with CD4+/CD25+/CD7– immunophenotype from a non–"bathing trunk" location, especially in a patient from endemic regions, raise suspicion for ATLL. T-cell receptor gene rearrangement is almost always positive, and the neoplasm usually demonstrates multiple mutations by next-generation sequencing study. [ABSTRACT FROM AUTHOR]

The whale shark (Rhincodon typus) is a filter-feeding organism that can be considered a sentinel species, and Bahía de los Ángeles (BLA) in the Gulf of California is an important sighting site for these elasmobranchs. This filter-feeding organism can be considered a pollutant sampler from the marine environment. Persistent organic pollutants are toxic compounds with high mobility and environmental persistence, bioaccumulation and trophic transfer. Among these are polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs). The present work aimed to determine concentrations of PAHs and OCPs in whale shark skin biopsies, collected in 2021 at BLA. Mean detected levels of PAHs and OCPs were 279.4 ng/g dw (dry weight) and 1478.1 ng/g dw, respectively. Analysis of similarities between the ordered sizes (4.2–7.6 m) and the concentrations of PAHs and OCPs indicated no significant differences. Individual PAHs detected indicate pyrogenic and petrogenic sources; the presence of pesticides at levels higher than those of hydrocarbons may be related to agricultural activity in the areas surrounding the Baja California peninsula. This study is the first report of PAH levels in R. typus for the Gulf of California and Mexico. [ABSTRACT FROM AUTHOR]

Background: An accurate diagnosis is the bedrock of the treatment of skin diseases. This study aimed to evaluate the correlation between clinical and pathological diagnosis of patients with skin disorders seen in dermatology units of Federal Medical Centre (FMC), Asaba, Delta State, and the University of Benin Teaching Hospital (UBTH), South-South Nigeria between 2019 - 2021., Material and Methods: This was a retrospective study of the charts of all patients seen in the dermatology units of FMC Asaba and UBTH who had skin biopsies for various skin diseases from 2019 to 2021. Biodata, clinical information, diagnosis, and histology results of these patients were collected using a questionnaire. One hundred and sixty-two (162) patients were excluded on account of the absence of a clinical diagnosis and a pathological conclusion of insufficient tissue sample., Results: 356 skin biopsies were included. The male-to-female ratio was 1:1.18 and most patients were aged 40 to 49 years 74 (20.8%) with a mean age of 38.28± 19.19. Papulosquamous skin disorders accounted for 141 of the clinical diagnoses (39.0%) Among the histology request forms filled, only 69 (19.4% ) had detailed clinical history. Clinico-pathological concordance (CPC) was recorded in 214 (60.1%) cases and discordance in 142 (39.9%), both the highest concordance and discordance percentages were among papulosquamous diseases (45.1% and 31.5% respectively). There was no significant association between the completeness of documentation of patient's clinical information and clinicopathological concordance., Conclusion: Although the CPC was above 50% in this study, better modalities of communication between dermatologists and pathologists is desired., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)