Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

Successful infliximab treatment in siblings with Netherton syndrome: Unveiling a novel SPINK5 gene variant and literature review.

Netherton syndrome (NS) is a rare autosomal recessive genodermatosis. In this article, we present two siblings with NS who harbour a novel variant in the SPINK5 gene and were treated with infliximab infusions. Both patients exhibited the characteristic clinical triad of NS, and their whole exome sequencing analysis revealed a homozygous variant, c.1820+53G>A, in the SPINK5 gene. Notably, this is the first documented instance of homozygosity for this particular variant. Despite the absence of a specific treatment, both patients achieved total clearance of the skin lesions, and a significant decrease in total IgE levels was documented.

EULAR study group on 'MHC-I-opathy': identifying disease-overarching mechanisms across disciplines and borders.

The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. OBJECTIVE: There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. METHODS: All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. RESULTS: A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). CONCLUSIONS: Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

Behçet's Disease: A Comprehensive Review on the Role of HLA-B*51, Antigen Presentation, and Inflammatory Cascade.

Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's pathogenesis, focusing on established genetic factors. Studies reveal that HLA-B*51 is the primary genetic risk factor, but non-HLA genes (ERAP1, IL-10, IL23R/IL-12RB2), as well as innate immunity genes (FUT2, MICA, TLRs), also contribute. Genome-wide studies emphasize the significance of ERAP1 and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between HLA-B*51 and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD's complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.

Phenotypic and molecular characterization of five patients with PIK3CA-related overgrowth spectrum (PROS).

Somatic and germline PI3K-AKT-mTOR pathway pathogenic variants are involved in several segmental overgrowth phenotypes such as the PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, and PTEN hamartoma tumor syndrome. In this study, we describe five patients with PROS. We identified by high-throughput sequencing four different somatic PIK3CA pathogenic variants in five individuals. The Glu726Lys variant, which was previously reported in megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, was identified in two patients with unclassified PROS. The Cys420Arg substitution, which was previously reported in CLOVES, was found in a patient with fibroadipose hyperplasia. Additionally, relatively rare pathogenic variants, His1047Tyr and Tyr1021Cys, were detected in two patients with MCAP. Therefore, we suggest performing deep sequencing of PIK3CA in all patients with suspected PROS, instead of targeted polymerase chain reaction for hotspot pathogenic variants.

Effect of Perineural Dextrose Injection on Ulnar Neuropathy at the Elbow: A Randomized, Controlled, Double-Blind Study.

OBJECTIVE: To compare perineural dextrose injection efficacy in the treatment of ulnar neuropathy at the elbow with a control group. DESIGN: Prospective double-blind randomized control study. SETTING: Training and research hospital. PARTICIPANTS: The study was completed with 40 patients with ulnar neuropathy at the elbow. INTERVENTION: Normal saline (0.9% sodium chloride) was injected in patients in the control group (n=20; mean age=38.1±10.7 years; median duration of symptoms=4.5 months), and 5% dextrose was injected in patients in the dextrose group (n=20; mean age=43.6±13.5 years; median duration of symptoms=5 months), perineurally under ultrasound guidance twice at 2-week intervals. Ultrasound-guided perineural injection of 1 cc each was administered into the ulnar nerve, 2 cm and 4 cm distal to the medial epicondyle, at the level of the medial epicondyle, and 2 cm and 4 cm proximal to the medial epicondyle. The amount of total fluid injected was 5 cc. MAIN OUTCOME MEASURE(S): At baseline and weeks 2, 4, and 12, the patients were evaluated with the Visual Analog Scale for pain and the Disabilities of the Arm Shoulder and Hand questionnaire for disability. Electrophysiological evaluation was performed with ulnar nerve conduction studies, and the ulnar nerve cross-sectional area was measured on ultrasonography. RESULTS: The improvements in pain, disability, ulnar motor nerve velocity, and ulnar nerve cross-sectional area in the dextrose group were superior to those in the control group, especially at weeks 4 and 12 (P<.001, using independent samples t tests). CONCLUSION: Perineural 5% dextrose may be an effective alternative therapy for those with ulnar neuropathy at the elbow for up to the 12th week.

The clinical and demographical characteristics of Turkish pediatric lymphedema patients: a multicenter study.

BACKGROUND: Reducing lymphedema-associated burden and disability in the pediatric setting requires improved awareness and understanding clinical properties of the lymphedema. The aim of this study was to evaluate the clinical and demographic characteristics of patients with pediatric lymphedema presented to different lymphedema centers in Turkey. METHODS: The socio-demographic and clinical characteristics of the children including age, gender, presence of genetic syndromes, duration of edema, site and stage of lymphedema and the received therapies were determined. Parental and children education on self-management techniques were recorded. RESULTS: A total of 122 children (female: 66, male: 56) with a mean age of 120.7 ± 71.2 months were included from 7 centers. Of them; 92% had primary, 8% had secondary lymphedema mostly due to infection and trauma. Lymphedema was part of a syndrome in 18% of the children. The most common site of involvement was the lower extremity, followed by upper extremity and genital involvement. Lymphedema was complicated in 17 % of children, mainly with a clinical picture of cellulitis, infection, and pain. The median duration of lymphedema was 41 (5-216) months. Although most of the children had stage 2 lymphedema, only 40% of them received treatment. The most commonly received treatment was compression therapy. No family or child was educated for self- care management before. DISCUSSION: In conclusion, pediatric lymphedema has a comparable gender distribution and usually involves the lower extremities. Although most of the children had advanced disease, more than half of the patients did not receive any treatment indicating the unmet need for management of lymphedema. The education of patients and/or children about self-management methods were lacking. We suggest educational activities for both families of children with lymphedema and health care providers, in order to facilitate early reference to lymphedema units and to receive prompt preventive and therapeutic approaches for this suffering condition.

Annual pattern and clinical characteristics of herpes zoster in immunocompetent children in a rural area.

This study aims to investigate the clinical signs, symptoms, complications and seasonal distribution of herpes zoster for otherwise healthy children and to demonstrate the outcome of varicella vaccinations on the herpes zoster incidence in a pediatric population. A retrospective study was conducted by using the data of the pediatric patients who were referred to two rural cities of Turkey, clinically diagnosed as Herpes Zoster (HZ). All participants were evaluated for clinical-epidemiological factors, signs, symptoms, complications and varicella vaccination status for HZ. This study was comprised of 69 pediatric patients (29 [42%] female and 40 [58%] male) who were diagnosed with HZ. The mean age was 10.57 (6 months-17) years old. The rash of HZ mostly appeared on the thoracic dermatome as seen in 29 patients. The findings revealed that among 56 unvaccinated patients of all, 25 (44.6%) had a painful rash, in comparison among vaccinated patients none reported pain as the characterization of shingles (P = .001). Annual distribution of cases showed two peaks (March and September), whereas in August no cases were detected. Of all participants, one patient had postherpetic neuralgia, who also had ophthalmic dermatomal involvement, and this was the only complication observed in this study cohort. In immunocompetent children, the most common involvement site was the thoracic dermatome. Our findings show that varicella vaccination has a protective role in the herpes zoster clinic, both by decreasing the prevalence and by making the infection course less severe.

Median nerve conduction studies in rabbits.

BACKGROUND: When planning nerve conduction studies using animal models, the sciatic nerve is often used and the upper extremity nerves are not preferred due to the size of laboratory animals. This study aimed to present the method and mean values of median nerve conduction studies in laboratory rabbits. Fifty-five six-month-old male New Zealand white rabbits weighing 2 to 2.5 kg were included in nerve conduction studies performed under anesthesia. The compound muscle action potential amplitude and distal latency values were recorded for the median motor nerve with the electrodes placed on the flexor digitorum superficialis muscle and tendon. RESULTS: A total of 110 median nerves were evaluated. The mean amplitude of the median nerve was 30.6 ± 6.8, mV the median nerve distal latency was 1.3 ± 0.2 ms, and the mean intensity of stimulation inducing a response was 2.5 ± 1 mA. CONCLUSIONS: The mean values obtained by the median motor nerve conduction method in this study can act as a guide for future nerve interventions undertaken in the upper extremities.

Hidradenitis suppurativa: Clinical characteristics and determinants of treatment efficacy.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that causes a significant decline in quality of life. There are numerous treatment options; however, real-life data on the efficacy of these treatments is limited. This study was performed in two centers to describe clinical characteristics and assess treatment outcome in a cohort of 139 patients with HS. Data on demographic and clinical characteristics, Hurley stage and comorbidities were collected from patient charts and evaluated retrospectively. Treatment response was measured with HS clinical response index (HISCR). Mean body mass index was 27.8±4.88. Inflammatory comorbidities were present in 23%. Among first-line drugs systemic doxycycline resulted in 60% HISCR followed by rifampicin-clindamycin combination (46.4%). Isotretinoin had the lowest HISCR (30.7%) in this group. For second-line therapies, all acitretin treated patients achieved response and patients treated with tumor necrosis factor alpha (TNF-α) inhibitors had the highest HISCR. Currently recommended first-line therapies have moderate efficacy in HS. Acitretin appears to be a reasonable alternative for the highly effective TNF-α inhibitors in patients with severe and resistant HS. Overall, these results support that excessive inflammatory response play an important role in pathogenesis of HS.

Bone loss in the affected forearm in patients with breast cancer-related lymphedema: a controlled study.

PURPOSE: We aimed to investigate the association between lymphedema and bone mass density (BMD) of affected and unaffected forearms in patients with breast cancer-related lymphedema (BCRL). We also explored whether there was a relationship between any disability and BMD on the affected side. METHODS: We evaluated 111 patients (53.75 ± 9.07) with unilateral lymphedema (group 1) and 61 patients (50.90 ± 12.44) without lymphedema (group 2) after breast cancer surgery. BMD was performed by dual-energy x-ray absorptiometry (DXA) in lumbar spine, femoral neck, and distal forearm on both sides. Functional situation was assessed by the Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire. RESULTS: The total Z score (p = 0.018), T score (p = 0.005), and BMD value (p = 0.014) were lower in the affected forearm than the unaffected forearm in group 1. There was no difference between the affected or unaffected sides in the total Z score (p = 0.394), T score (p = 0.518), and BMD value (p = 0.629) in group 2. The DXA measurements in terms of the total forearm Z, T scores, and BMD value on the affected side were statistically significantly different between the groups. There was no difference between groups in the femur neck and lumbar total Z and T scores. There was also a positive correlation between the QuickDASH scores and lymphedema stage (r = 0.469, p = 0.001) and the duration without treatment of lymphedema (r = 0.298, p = 0.02) in group 1. CONCLUSION: We recommend early diagnosis and treatment of lymphedema for the protection of upper extremity disability and localized osteoporosis in patients with BCRL.

Lichen sclerosus associated with Nd:YAG laser therapy.

Laser is the most efficient and popular method in hair removal. The most common side effects of laser assisted hair removal are pain, erythema, edema, hypopigmentation, hyperpigmentation, blistering, crusting, erosions, purpura, folliculitis, and scar formation ( 1 ). Herein, for the first time we describe a case of lichen sclerosus (LS) following hair removal with long pulsed 1064 nm Nd:YAG laser therapy.

Long-Term Follow-Up Results of Topical Imiquimod Treatment in Basal Cell Carcinoma.

BACKGROUND: Imiquimod 5% topical cream is approved for treatment of superficial basal cell carcinoma (BCC). Data on the long-term efficacy and usage in other BCC subtypes are scarce. OBJECTIVE: Evaluation of long-term safety and efficacy of topical imiquimod treatment in various BCC subtypes and locations, with individualized treatment duration. MATERIALS AND METHODS: Histopathologically confirmed BCCs treated solely with topical imiquimod were identified retrospectively and included in this study. Clinical and histopathologic tumor clearances were the primary end point. After treatment was concluded, patients were examined every 3 to 6 months. RESULTS: In total, 24 BCC samples from 22 patients (F:M = 9:13; mean age: 73.5 years, SD: 10.767) were evaluated. The majority of the lesions were located in the head and neck area (83%). Mean treatment duration until complete clearance was 15.7 ± 6.9 weeks (6-28 weeks). Imiquimod was discontinued in 3 lesions, due to either clinically or histopathologically insufficient response. During follow-up, 2 lesions recurred, at 42 and 50 months after treatment. During a mean follow-up time of 72.7 (SD = 9) months, 79.1% of the lesions were cured without local recurrence. CONCLUSION: Although imiquimod is only approved for superficial BCC, treatment success was high among the study patients with various histological subtypes, with good long-term cosmetic results.

Risk Factors and Frequency of Ingrown Nails in Adult Diabetic Patients.

The present study evaluated the properties of nails, frequency of ingrown nails in patients with type 2 diabetes mellitus (DM), risk factors for developing ingrown nails, and effect of diabetic polyneuropathy and vasculopathy on the development and outcome of ingrown nails. Our 6-month epidemiologic prospective study included 300 patients with type 2 DM attending a DM outpatient clinic for routine examinations. The general characteristics and foot changes of the study population were investigated. Diabetic polyneuropathy and vasculopathy were evaluated using a biothesiometer, monofilament tests, and arterial Doppler ultrasonography. The frequency of ingrown nails was 13.6%. Multivariate analysis with logistic regression showed that body mass index (odds ratio [OR] 1.077, 95% confidence interval [CI] 1.007 to 1.15; p = .03), previous trauma (OR 2.828, 95% CI 1.017 to 7,867, p = .042), a weak dorsalis pedis pulse (OR 2.72, 95% CI 1.17 to 6.30, p = .02), trimming type (OR 2.3, 95 CI 1.06 to 4.98), p = .35), onychogryphosis (OR 9.036, 95% CI 2.34 to 34.87, p = .001), and subungual hyperkeratosis (OR 4.3, 95% CI 1.99 to 9.3, p = .001) were predictive variables for ingrown nails in our population. The incidence of onychomycosis was significantly greater in patients with ingrown nails (p = .032) than in patients without ingrown nails. The nail curvature ratio was greater in the patients with ingrown nails than in the group with normal nails. Arterial Doppler ultrasound examinations showed peripheral arterial disease in 19 patients (46.9%) with ingrown nails. The prevalence of ingrown nails was greater in the patients with DM than in the healthy population. Our results indicate that nail type, nail morphology, and diabetic vasculopathy affect the formation and evolution of ingrown nails.

Skin-Dominant Phenotype in a Patient with H Syndrome: Identification of a Novel Mutation in the SLC29A3 Gene.

H syndrome (OMIM 602782) is a very rare autosomal recessive genodermatosis with multisystem involvement. Hallmarks of this disorder are juvenile onset and progressive, hyperpigmented, hypertrichotic lesions with histiocytic infiltration. Associated systemic manifestations form a long list, and there is high variability between patients. In some patients, dysmorphic and other systemic features may be so subtle that the disorder may readily be mistaken as an acquired skin disease and treated as such. Herein, we report a novel homozygous c.1339G>A (p.Glu447Lys) mutation in the SLC29A3 gene in a patient with skin-dominant presentation of H syndrome. Additionally, due to the present case, double superior vena cava can be added to the list of possible cardiovascular manifestations of H syndrome.