Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa.

BACKGROUND: Results of randomized clinical trials show great variation in response to treatment with adalimumab (ADA) in hidradenitis suppurativa (HS). This varied response may be associated with genetic polymorphisms. OBJECTIVES: The aim of the study was to study the association between carriage of single nucleotide polymorphisms (SNPs) in the promoter of the tumor necrosis factor (TNF) gene and their response to ADA. METHODS: Patients with moderate to severe HS who received ADA treatment for at least 12 weeks were enrolled. SNPs were analyzed with PCR-restriction fragment length polymorphism. Hidradenitis Suppurativa Clinical Response (HiSCR) score, International Hidradenitis Suppurativa Severity Scoring System 4 (IHS4) score, inflammatory lesion (AN) count, and draining tunnel (dT) count were collected at weeks 0, 12, 24, 36, and 48. RESULTS: HiSCR response after 12 weeks of ADA treatment was 71.8% among carriers of the common GGG haplotype and 50.0% among carriers of minor frequency SNP haplotypes (p: 0.031; odds ratio: 0.39). This significant difference persisted until week 36. Carriers of minor frequency SNP haplotypes also had a lower relative decrease of the AN count at weeks 12 and 24; the dT count and IHS4 were not statistically different between the two groups. CONCLUSIONS: Carriage of at least one minor frequency SNP haplotype of the promoter of the TNF gene is associated with a decreased response to ADA. This association may have an impact on treatment decision-making.

External Validation of the IHS4-55 in a European Antibiotic-Treated Hidradenitis Suppurativa Cohort.

BACKGROUND: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 (IHS4-55) score. It was validated in datasets of adalimumab and placebo-treated HS patients. External validation is an important aspect of clinical outcomes. OBJECTIVES: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. METHODS: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients were used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses, and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCIDs) for Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) Pain, and NRS Pruritus were analyzed. RESULTS: Data were obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p < 0.001). Additionally, IHS4-55 achievers had an odds ratio for achieving the MCID of DLQI, NRS Pain, and NRS Pruritus of 2.16 (95% CI 1.28-3.65, p < 0.01), 1.79 (95% CI 1.10-2.91, p < 0.05), and 1.95 (95% CI 1.18-3.22, p < 0.01), respectively. CONCLUSIONS: This study shows the external validity of the novel IHS4-55 by demonstrating a significant association between IHS4-55 achievement and a reduction in inflammatory lesion counts as well as achievement of MCIDs for DLQI, NRS Pain, and NRS Pruritus in an antibiotic-treated cohort. These findings support the use of the IHS4-55 as a novel primary outcome measure in clinical trials.

The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: Results of a prospective European cohort study.

BACKGROUND: Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current hidradenitis suppurativa guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes. OBJECTIVE: To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin. METHODS: A prospective, international cohort study performed between October 2018 and August 2019. RESULTS: In total, 63.6% of the included 283 patients received oral tetracyclines, and 36.4% were treated with clindamycin and rifampicin. Both groups showed a significant decrease in International Hidradenitis Suppurativa Severity Score System from baseline (both P < .001). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 40.1% and 48.2% of patients, respectively (P = .26). Patient characteristics or disease severity were not associated with the attainment of HiSCR or the minimal clinically important differences for the Dermatology Life Quality Index and pain. LIMITATIONS: Cohort study. Respectively, 23.9% and 19.4% of patients had to be excluded from the HiSCR analysis for the tetracycline and combination therapy group because of a low abscess and nodule count at baseline. CONCLUSION: This study shows significant efficacy of both tetracycline treatment and clindamycin and rifampicin combination therapy after 12 weeks in patients with hidradenitis suppurativa. No significant differences in efficacy were observed between the 2 treatments, regardless of disease severity.

Adalimumab Dose Intensification in Recalcitrant Hidradenitis Suppurativa/Acne Inversa.

BACKGROUND: Adalimumab is the only approved compound for the treatment of adult patients with moderate-to-severe hidradenitis suppurativa (HS) who did not respond to a systemic classical treatment. Despite its significant short- and long-term efficacy, a percentage of patients do not respond sufficiently. Moreover, some primary responders experience a response loss with time. OBJECTIVE: To analyse the effectiveness of adalimumab dose intensification in HS patients. METHODS: A case series of adalimumab 80 mg/week subcutaneously (s.c.) compassionate use in patients with HS, who did not respond sufficiently or in primary responders with progressive response loss to the registered adalimumab dose of 40 mg/week s.c. Patients were collected and evaluated retrospectively. Patients' data were extracted from medical records. RESULTS: The 14 patients collected were Caucasian with HS of Hurley stage II-III and moderate or severe International HS Severity Score System (IHS4) stage. Adalimumab dose intensification significantly improved IHS4 score, Pain Index, HS-Physician Global Assessment, pain, and Cardiff Dermatology Life Quality Index. Two young female patients with HS and Crohn's disease developed psoriatic lesions during the treatment with adalimumab 80 mg/week s.c. CONCLUSION: An enhanced level of effectiveness was assessed in the majority of the HS patients treated with adalimumab dose intensification (80 mg/week s.c.). Larger studies are required to evaluate this observation.

Correlation of Specific Inflammatory Markers With the Occurrence of Depression in Patients With Psoriasis and Their Use as Biomarkers for the Diagnosis of Depression.

INTRODUCTION: Psoriasis is a systemic disease of the skin and nails associated with a wide range of comorbidities such as depression, psoriatic arthritis and metabolic syndrome. OBJECTIVES: The study aimed to examine a potential association between inflammatory markers (C- reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and depression in patients with psoriasis. METHODS: A total of 80 individuals were enrolled in the study. Case participants included 28 patients diagnosed with Psoriasis (Beck Depression Inventory-II: :0-13) and 24 patients diagnosed with Psoriasis and Depression (Beck Depression Inventory-II:14-63). Twenty-eight (28) healthy participants comprised the control group.Psoriasis severity was evaluated by using Psoriasis Area and Severity Index, Physician Global Assessment, Body Surface Area and Dermatology Life Quality Index. Written approval was obtained for its use in this study: Cardiff University (09/2015). Other factors considered in the study were obesity using the Body Mass Index, the levels of stress using the Beck Anxiety Inventory, and the presence of insomnia using the Athens Insomnia Scale. Blood draws and inflammatory markers measurements were performed for all participants. RESULTS: Both CRP and ESR levels were higher in the case group (ie Psoriasis and Depression and Psoriasis) compared to healthy controls. Furthermore, psoriatic patients with depression showed increased CRP and ESR levels compared to those of psoriatic patients without depression. CONCLUSIONS: The evaluation of both CRP and ESR and their use to detect the presence of depression in patients with psoriasis can be an important tool for their holistic treatment of theirs.

Eccrine Poroma: Pathogenesis, New Diagnostic Tools and Association with Porocarcinoma-A Review.

Eccrine poroma (EP) is a relatively rare benign adnexal neoplasm that usually affects elderly patients. Its pathogenesis is still under investigation, but recent gene studies have revealed gene fusions as key incidences resulting in oncogenetic pathways. It often presents as a solitary, firm papule, mostly asymptomatic, located on the soles or palms. Due to its clinical and dermoscopic variability, it is characterized as the great imitator. We performed a literature review, aiming to summarize current data on the pathogenetic mechanisms, new dermoscopic features, and novel diagnostic tools that may aid in early diagnosis and proper management of this rare adnexal tumor. Furthermore, we reviewed the possible pathogenetic associations between EP and its malignant counterpart, namely eccrine porocarcinoma. This systematic approach may aid in understanding the pathogenetic mechanisms and how to use novel histopathologic markers and imaging methods to overcome the diagnostic dilemma of this rare tumor.

Narrative Review of Drug-Associated Nail Toxicities in Oncologic Patients.

INTRODUCTION: Nail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy. OBJECTIVES: We aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management. METHODS: Retrieved literature from PubMed registry database was reviewed to include all articles published up to May 2021 relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of oncologic treatment-induced nail toxicity. The internet was searched for relevant studies. RESULTS: A wide spectrum of nail toxicities is associated with both, conventional and newer anticancer agents. The frequency of nail involvement, especially with immunotherapy and new targeted agents remains unknown and patients with different cancer types receiving different regimens may develop the same nail disorder, whereas patients with the same type of cancer under the same chemotherapeutic treatment may develop different types of nail alterations. The underlying mechanisms of the varying individual susceptibility and the diverse nail responses to various anticancer treatments need further investigation. CONCLUSION: Early recognition and treatment of nail toxicities can minimize their impact, allowing better adherence to conventional and newer oncologic treatments. Dermatologists, oncologists and other implicated physicians should be aware of these burdensome adverse effects in order to guide management and prevent impairment of patients' quality of life.

The potential role of microorganisms in the development of rosacea.

Rosacea is a chronic cutaneous disorder characterized by centrofacial persisting erythema, telangiectases, papules, pustules, edema, phymas and ocular involvement. Despite being one of the most common skin disorders, its pathogenesis remains unclear and controversial. Although the disease triggering factors are well recognized, the underlying causes of rosacea have not yet been identified. Several different postulates about its pathogenesis can be found in the medical literature. Abnormalities of the pilosebaceous unit, as well as genetic, vascular, inflammatory, environmental and microbial factors have been described. The microorganisms that have been associated include Helicobacter pylori, Demodex folliculorum, Staphylococcus epidermidis, and Chlamydia pneumonia; all the studies have been inconclusive. We review currently available scientific data on the potential pathogenetic role of microorganisms in the development of rosacea.

A case series of skin manifestations of infective endocarditis in contemporary era: just another book finding or a useful clinical sign?

BACKGROUND: Infective endocarditis (IE) is a disease of high morbidity and mortality. Infective endocarditis rarely involves skin manifestations in the contemporary era. The identification of typical skin lesions could be helpful in establishing early diagnosis of IE. CASE SUMMARY: We present four cases of IE hospitalized in our institution within a 12-month period. All patients were young and had skin manifestations on initial presentation (petechiae, splinter haemorrhages, Janeway lesions, and Osler's nodes), which led to a high clinical suspicion of IE confirmed by echocardiography and positive blood cultures. All cases had a complicated course. One patient died and the other three had prolonged hospital stay due to variable complications. DISCUSSION: Clinicians should always assess for skin manifestations in patients with fever especially when suspicion of IE is high. Occurrence of skin lesions in the course of IE may be associated with higher rate of complications and worse prognosis.

Efficacy of adalimumab in moderate to severe hidradenitis suppurativa: Real life data.

Hidradenitis suppurativa (HS) is a relapsing, inflammatory disease characterized by painful nodules, abscesses, sinuses track formation and scarring. HS has a great impact on patients' quality of life and its treatment may be really challenging. Adalimumab provides a new therapeutic option for HS. Our aim was to assess the therapeutic potential of adalimumab on patients with HS based on the data from the daily clinical practice of an HS Outpatient Clinic. 19 patients with clinically evident moderate to severe HS, under adalimumab treatment for at least 24 week, participated in this observational, retrospective study. The Hidradenitis Suppurativa Physician's Global Assessment scale, Modified Santorius scale and Dermatology Life Quality Index (DLQI) at baseline, week 4, week 12 and week 24 were retrieved from the records. Both Modified Santorius score and DLQI were significantly decreased during the weeks of evaluation (Friedman's test; P < 0.001). The proportion of patients who achieved clinical response was 10.5% (n = 2) at week 4, 42.1% (n = 8) at week 12 and 63.2% (n = 12) at week 24. Treatment with adalimumab was linked with both clinical remission of HS and improvement of patients' quality of life.

Spectrum of Autoimmune Bullous Diseases in Northern Greece. A 4-year Retrospective Study and Review of the Literature.

Bullous Diseases Unit at the 2nd Department of Dermatology and Venereology, Aristotle University of Thessaloniki was founded with the aim to provide the optimal diagnostic approach and treatment of patients with autoimmune bullous diseases (AΙBD). We processed all AIBD files of patients diagnosed from 2011 to 2014 in order to record all epidemiological data and therapeutic manipulations during monitoring. 57 patients were diagnosed with intraepidermal and 62 with subepidermal bullous diseases. There were 51 cases (89%) of pemphigus vulgaris (PV) and 6 (11%) of pemphigus foliaceus (PF), whereas 45 (73%) patients were diagnosed with bullous pemphigoid (BP), 9 (14%) with mucous membrane pemphigoid (MMP), 3 (5%) with pemphigoid gestationis (PG), 3 (5%) with linear IgA dermatosis (LAD), 1 (2%) with epidermolysis bullosa aquisita (EBA), and 1 patient with an undefined subepidermal AIBD. The mean age of patients within the pemphigus spectrum was 57 years. In the pemphigoid spectrum, the mean age was 72 years. Comorbidities were reported with increasing frequency, as well as treatment options other than systemic corticosteroids, such as adjuvant immunosuppressive agents, which were used to achieve complete remission. This is a report from a tertiary AIBD Referral Center in northern Greece. Our data from a 4-year period contribute to the completion of the global geographic incidence map of AIBD.

Association of ustekinumab and briakinumab with major adverse cardiovascular events: An appraisal of meta-analyses and industry sponsored pooled analyses to date.

Safety concerns have been raised regarding possible association of major adverse cardiovascular events (MACEs) with use of anti-IL-12/23 biologic agents for the treatment of chronic plaque psoriasis (CPP). Ten MACEs have been recorded in actively-treated patients during the placebo-controlled phase of phase II and III studies compared with zero events in placebo-treated patients, along with a total of 53 MACEs (26 ustekinumab, 27 briakinumab) and five cardiovascular deaths (1 ustekinumab, 4 briakinumab) across all phases of these studies. Two industry-independent meta-analyses of randomized, double-blind, placebo-controlled, monotherapy trials calculated risk for MACEs. One detected statistically significant increase in cardiovascular risk using Peto method (p = 0.04), while the other utilized Mantel-Haenszel fixed-effects model with absolute risk differences as effect measure, but did not achieve significance (p = 0.11). Statistical theory reports that Peto method is more suitable for meta-analyses of studies with baseline event rates of 1% or less and randomization ratios ranging from 1:5 to 1:1 as is the case in these meta-analyses. Potential of anti-IL-12/23 biologic agents to further increase cardiovascular morbidity cannot be excluded and a class effect cannot be denied. Clinicians should screen CPP patients for manageable cardiovascular risk factors before initiating anti-IL-12/23 agents along with intensive monitoring of these patients.

Parry-Romberg syndrome.

BACKGROUND: Parry-Romberg syndrome (PRS) or idiopathic hemifacial atrophy is a rare neurocutaneous syndrome. It is characterized by slowly progressive atrophy, located on one side of the face, primarily involving the skin, fat and connective tissue. PRS seems to overlap with "en coupe de sabre" morphea. MAIN OBSERVATIONS: We present a case of hemifacial atrophy in a 14-year-old boy treated with topical calcipotriol-betamethasone ointment. The diagnosis of PRS was established mainly based on the clinical findings and histological picture. The time to diagnosis was almost 9 years, similar to the mean time reported in the literature. CONCLUSIONS: Understanding the pathogenesis and stopping disease progression is important as it can cause severe disfigurement and has neurological and psychiatric complications. Not much is known about the efficacy of agents used in the treatment of this syndrome making treatment decision very difficult. Possible complications, pathophysiology and therapeutic options are being discussed.

Resistant pityriasis lichenoides et varioliformis acuta in a 3-year-old boy: successful treatment with methotrexate.

Pityriasis lichenoides et varioliformis acuta (PLEVA) represents the acute clinical subtype of pityriasis lichenoides (PL) and its occurrence is relatively common during childhood. Diagnosis and treatment may sometimes pose certain difficulties. We present the recalcitrant case of a 3-year-old boy with an asymptomatic polymorphic eruption consisting of multiple, scattered, 0.5 cm, round to ovoid, erythematous papules covered in places with a fine scale, vesicles and superficial erosions with thick hemorrhagic crusts. The correlation of the clinical features with the lesional histopathology favored the diagnosis of PLEVA. No first-line treatment scheme succeeded in controlling the eruption of new lesions. The only therapeutic approach that eventually managed to cease the disease evolution was the combination of prednisolone and methotrexate.