Heparin-induced bullous haemorrhagic dermatosis is an uncommon cutaneous adverse reaction to heparin, thought to be under-reported owing to its relatively asymptomatic presentation and favourable ...prognosis. This vesiculobullous condition is largely self-limiting and tends to resolve spontaneously despite continued anticoagulant therapy. Correct identification can reassure clinicians and patients alike.
Abstract Trimethylaminuria (TMAU) is a rare metabolic disorder resulting in the accumulation of trimethylamine (TMA), which is a foul-smelling metabolite that is excreted in bodily fluids and exudes ...a characteristic odour of rotting fish. Although the condition is not life-threatening, the psychological and social consequence can be devastating. Herein, we present the case of a 35-year-old woman with a diagnosis of TMAU. This case outlines the methods by which a diagnosis of TMAU can be made, while also magnifying the negative psychosocial impact of this rare diagnosis. It also reflects real-world experience with the currently available therapeutic options. TMA is produced in the gastrointestinal tract from dietary precursors such as choline (present in eggs, liver and poultry), trimethylamine N-oxide (TMAO; found in marine fish) and carnitine (found in meat). Primary trimethylaminuria is due to a mutation in the FMO3 gene, leading to the inability to oxidize this amine to the nonodorous metabolite (TMAO) (Antoñanzas J, Querol-Cisneros E, Alkorta-Aranburu G et al. Primary trimethylaminuria syndrome: more than an unpleasant odor. Int J Dermatol 2023; 62: e176–8). At present, over 40 variants in FMO3 associated with TMAU have been identified. Secondary or acquired TMAU is the result of a combination of factors including increased consumption of dietary precursors, gut dysbiosis, hepatic impairment and hormonal fluctuations resulting in an accumulation of TMA. Treatment regimens involve limiting precursors intake, using acidic soaps to reduce the volatility of excreted TMA, targeting gut microbiota, and the use of oral sequestering agents (Schmidt AC, Leroux JC. Treatments of trimethylaminuria: where we are and where we might be heading. Drug Discov Today 2020; 25: 1710–17). However, current treatment options have had limited therapeutic effect. Referral to metabolic specialists for correct nutritional support and referral to psychiatry is paramount for these patients. As evident from our patient’s viewpoint, this diagnosis can have a lifelong impact on social engagement and psychological health.
Abstract
Glycogenic acanthosis (GAc) is a benign epithelial disorder, commonly observed in the oesophagus during endoscopy as multiple raised nodules affecting otherwise normal oesophageal mucosae ...(Tsai SJ, Lin CC, Chang CW et al. Benign esophageal lesions: endoscopic and pathologic features. World J Gastroenterol 2015; 21:1091). Despite its indolent disease course, oesophageal GAc is a minor diagnostic criterion for Cowden syndrome (CS). Glycogenic acanthosis affecting tissues other than the oesophagus is extremely rare. There have only been six cases of oral GAc reported to date, with no confirmed reports of GAc affecting the lip. We present the case of a 65-year-old White man with a 6-month history of asymptomatic white papules on the left lower lip. He was a lifelong nonsmoker. His past medical history was notable for colorectal cancer, which was in remission posthemicolectomy. He had also undergone ablative treatment for nasal polyps. He had no history of gastro-oesophageal reflux disease, or of thyroid disease, benign or malignant. Prominent facial actinic damage was present, and a biopsy was performed to rule out dysplasia. Histology demonstrated thickened hyperplastic epidermis and cytoplasmic clearing in the superficial epidermis. Keratinocytes with enlarged cytoplasm were positive on periodic acid–Schiff staining, supporting a diagnosis of GAc. On review, 3 months later, a single residual white papule was observed on the left lower lip. There were no other cutaneous features suggestive of CS. CS is caused by mutations in PTEN and is part of a spectrum of disorders known as PTEN hamartoma tumour syndrome (PHTS). It is associated with increased risk of solid-organ malignancies. Of the prior six reported cases of oral GAc, only one (Nishizawa A, Satoh T, Watanabe R et al. Cowden syndrome: a novel mutation and overlooked glycogenic acanthosis in gingiva. Br J Dermatol 2009; 160:1116–18) had a confirmed association with CS. Our patient remains under endoscopic surveillance but does not currently meet the criteria for either diagnosis or further genetic evaluation of CS. Oral glycogenic acanthosis may be an under-recognized entity due to its subtle clinical presentation. Biopsy and full-skin examination are warranted in suspected cases, to identify any association with an underlying genodermatosis.
Our article discusses current challenges of prescribing isotretinoin as well as reflecting on results of a recent survey of Irish dermatologists to assess baseline prescribing practice in relation to ...pregnancy prevention compliance, psychiatric assessment and assessment of sexual dysfunction. It highlights compliance and satisfaction with current Irish guidance and a need for further studies in key prescribing areas.
A 45-year-old woman provides her perspective on living with a rare disorder, trimethylaminuria, also known as ‘fish odour syndrome’. She describes the negative quality-of-life impact this diagnosis ...has had on her life, and feeling misunderstood and isolated with this diagnosis.
Disease severity in patients with atopic dermatitis (AD) is directly correlated with colonization by Staphylococcus aureus.1 An increasing body of evidence now also supports a role for S aureus in ...the pathogenesis of AD in genetically susceptible subjects.2 Increased prevalence of S aureus preceding and coinciding with AD onset in an infant cohort suggests that early skin colonization can contribute to the development of clinical AD.3 However, these findings only partially explain the complex role of this organism given that another birth cohort4 did not demonstrate S aureus colonization before development of infantile AD but did show a protective effect of commensal staphylococci against later development of AD. Research is currently underway to investigate the effects of dupilumab, an anti–IL-4 receptor α blocker targeting the TH2 cytokines IL-4 and IL-13 in S aureus–colonized versus noncolonized patients with AD.12 However, active infection causing flares still requires the use of antibiotics, highlighting the role of alternative approaches, including active and passive vaccination strategies (Table I).13-23 Passive immunization strategies using mAbs against specific S aureus toxins are under investigation, although typically as adjuncts to standard antibiotic regimens in high-risk patient groups. Reference Active prophylactic vaccines 1 NDV-3: recombinant Candida albicans Als3p adhesion protein (homologous to S aureus surface proteins) with alum adjuvant NovaDigm Therapeutics, Brookline, Mass 1 2 2 NCT01273922 NCT02996448 NCT03455309 Schmidt et al, 201213 Not published Not published 2 S aureus capsular polysaccharides CP5 and CP8 conjugated to TT, mutated detoxified AT and ClfA ± AS03B adjuvant GlaxoSmithKline, Research Triangle Park, NC 1 NCT01160172 Levy et al, 201514 3 STEBVax: recombinant SEB with alum adjuvant Integrated BioTherapeutics, Gaithersburg, Md 1 NCT00974935 Chen et al, 201615 4 HI, SpA5, mSEB, MntC recombinant proteins and aluminum phosphate adjuvants Olymvax, Chengdu, China 1 1 NCT02820883 NCT02804711 Not published Not published 5 SA3Ag/SA4Ag Pfizer, New York, NY SA3Ag: CP5, CP8, conjugated to CRM197 and recombinant ClfA SA4g: CP5, CP8, conjugated to CRM197, recombinant ClfA and MntC 1 1/2 1/2 1 1/2a 2b NCT01018641 NCT01364571 NCT01643941 NCT02364596 NCT02492958 NCT02388165 Nissen et al, 201516 Marshall et al, 201617 Frenck RW Jr, et al, 201718 Creech et al, 201719 Begier et al, 201720 Not published Not published 6 Recombinant α-toxoid (rAT) and subunit of Panton-Valentine leukocidin (rLukS-PV).
IMPORTANCE: Daylight photodynamic therapy using topical methyl 5-aminolevulinic acid (MAL) for actinic keratoses (AKs) is as effective as conventional photodynamic therapy but has the advantage of ...being almost pain free. Daylight photodynamic therapy, however, requires dry and warm weather conditions. OBJECTIVE: To establish if topical MAL photodynamic therapy using a white light light-emitting diode (LED) lamp is as effective and well-tolerated as daylight photodynamic therapy for the treatment of AKs. DESIGN, SETTING, AND PARTICIPANTS: Overall, 22 men with significant photodamage and a high number of AKs were enrolled in this prospective, randomized, single-blind study, employing a split-scalp design, comparing the effectiveness and adverse effects of daylight photodynamic therapy and artificial white light (AWL) LED photodynamic therapy for the treatment of AKs on the forehead and scalp. Organ transplant recipients were excluded. Patients were treated and evaluated at an academic tertiary referral dermatology center. Treatment lasted from April 2014 to July 2014 and follow-up visits occurred for 9 months posttreatment. INTERVENTIONS: Two symmetrical treatment fields were defined and AKs counted, mapped, and photographed at baseline, 1, 3, 6, and 9 months. Patients had half of their scalp treated with daylight photodynamic therapy and the other half treated with AWL photodynamic therapy 1 week apart and randomly allocated. MAL was applied, and treatment commenced 30 minutes later and lasted 2 hours. Irradiance, illuminance, and light spectra measurements were performed. The integrated dose in J/cm2 was measured. The effective light dose, weighted to the absorption spectrum for protoporphyrin IX, was calculated. MAIN OUTCOMES AND MEASURES: The primary end point was the reduction in total AK count per treatment field. Secondary end points included adverse effects and patient satisfaction. RESULTS: We enrolled 22 men with a median age of 72 years (range, 47-85 years) at baseline, the total (median of AKs per field) were 469 (20.5) for the DPDT group and 496 (20.5) for the AWLPDT group (P = .34). The median number and percentage of reduction in AKs per field were 12 and 62.3% for DPDT and 14 and 67.7% for AWLPDT at 1 month (P = .21 and P = .13, respectively). There was no significant difference in the reduction percentage of AKs for either treatment at 1, 3, and 6 months. At 9 months, the median number and percentage of reduction in AKs per field was 9.0 and 48.4% for DPDT and 12.0 and 64.4% for AWLPDT (P = .13 and P = .05, respectively). Pain was reported by 14 patients with DPDT and 16 patients with AWLPDT (median maximum score out of 100, 4 vs 6; P = .51). Moderate erythema was reported by 9 patients after DPDT and 14 patients after AWLPDT. On a scale of 0 (intolerable) to 10 (very tolerable) patients rated DPDT as 9.5 and AWLPDT as 9 (P = .37). CONCLUSIONS AND RELEVANCE: Photodynamic therapy using an AWL source was as effective and well-tolerated as daylight photodynamic therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02520700
Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen ...associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S. aureus have had limited efficacy and S. aureus-associated temporal disease flares are synonymous with AD. An alternative approach is an anti-S. aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti-S. aureus responses; however, correlates of T cell immunity against S. aureus in AD have not been identified. We identify a systemic and cutaneous immunological signature associated with S. aureus skin infection (ADS.aureus) in a pediatric AD cohort, using a combined Bayesian multinomial analysis. ADS.aureus was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct Th1 and Th2 cells to skin. Systemic CD4+ and CD8+ T cells, except for Th2 cells, were suppressed in ADS.aureus, particularly circulating Th1, memory IL-10+ T cells, and skin-homing memory Th17 cells. Systemic γδ T cell expansion in ADS.aureus was also observed. This study suggests that augmentation of protective T cell subsets is a potential therapeutic strategy in the management of S. aureus in AD.
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