Bacterial Skin Dysbiosis in Darier Disease.

INTRODUCTION: Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity. METHODS: All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing. RESULTS: Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively. CONCLUSION: Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.

[TRANSLATIONAL MEDICINE IN DERMATOLOGY- FURTHER PROMOTING PSORIASIS RESEARCH].

INTRODUCTION: Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide. Translational medicine, which focuses on treating and analyzing diseases caused by translational factors, is becoming increasingly relevant in the field of psoriasis research. This review aims to display the current literature on the role of translational medicine in the treatment and understanding of psoriasis. We found that translational factors such as protein kinases and cytokines play a key role in the development and progression of psoriasis. Additionally, current treatments for psoriasis, such as biologics, target these translational factors to reduce inflammation and improve skin condition. Furthermore, studies have shown that genetic variations in translational-related genes can also contribute to the development of psoriasis. This highlights the importance of translational medicine in understanding the underlying mechanisms of psoriasis and developing increasingly effective treatments for this debilitating disease.

Beyond simple habituation: Anthropogenic habitats influence the escape behaviour of spur-winged lapwings in response to both human and non-human threats.

Habitat development may affect wildlife behaviour, favouring individuals or behaviours that cope better with perceived threats (predators). Bolder behaviours in human-dominated habitats (HDH; e.g. urban and rural settlements) may represent habituation specifically to humans, or a general reduction in predator-avoidance response. However, such carry-over effects across threat types (i.e. beyond humans) and phases of the escape sequence have not been well studied to date. Here we investigated escape behaviours of a locally common wader species, the spur-winged lapwing Vanellus spinosus. We assayed their flight initiation distance (FID) and subsequent escape behaviours in agricultural areas and in HDH. We found that lapwings in HDH were bolder, and that the difference was manifested in several phases of the predator-avoidance sequence (shorter FIDs, shorter distances fled, and a higher probability of escape by running vs. flying). When re-approached (by an observer) after landing, lapwings in HDH were also more repetitive in their FID than those in other habitats. To determine whether this apparent bolder behaviour in HDH areas is merely a consequence of habituation to humans or represents a broader behavioural change, we introduced an additional threat type-a remotely-operated taxidermic jackal ('Jack-Truck'). Finding bolder responses in the HDH to the human threat alone (and not to the Jack-Truck) could have supported the habituation hypothesis. In contrast, however, we found a bolder response in the HDH to both threat types, as well as a correlation between their FIDs across different sites. These bolder behaviours suggest that HDH impose a broader behavioural change on lapwings, rather than just simple habituation. Overall, our findings demonstrate how FID trials can reveal strong behavioural carry-over effects of HDH following human and non-human threats, including effects on the subsequent phases of escaping the predator. Further, FID assays may reveal consistent behavioural types when assessed under field conditions, and offer a direct way to differentiate among the various poorly understood and non-mutually exclusive mechanisms that lead to behavioural differences among organisms in HDH. The mechanistic perspective is essential for understanding how rapid urbanization impacts wildlife behaviour, populations, and the range of behaviours within them, even in species apparently resilient to such environmental changes.

Adult Henoch-Schönlein Purpura: Comprehensive Assessment of Demographic, Clinical, and Histopathological Features as Predictors for Systemic Involvement.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small-vessel IgA-predominant vasculitis. A major challenge in managing adult HSP is the difficulty assessing the risk of systemic involvement. There is currently a paucity of data in this area. OBJECTIVE: The objective of this study was to determine demographic, clinical, and histopathological features associated with systemic involvement in adult HSP. METHODS: In this retrospective study, we reviewed demographical features and clinical and pathology data of 112 adult HSP patients seen at Emek Medical Center between January 2008 and December 2020. RESULTS: Of these patients, 41 (36.6%) had renal involvement, 24 (21.4%) had gastrointestinal tract involvement, and 31 (27.7%) had joint involvement. Age >30 years (p = 0.006) at diagnosis was an independent predictor of renal involvement. Platelet count (<150 K/µL) (p = 0.020) and apoptosis of keratinocytes on skin biopsy (p = 0.031) were also associated with renal involvement. History of autoimmune disease (p = 0.001), positive c-antineutrophil cytoplasmic antibody (p = 0.018), positive rheumatoid factor (p = 0.029), and elevated erythrocyte sedimentation rate (p = 0.04) were associated with joint involvement. Female sex (p = 0.003), Arab race (p = 0.036), and positive pANCA (p = 0.011) were associated with gastrointestinal tract involvement. LIMITATIONS: This study is retrospective. CONCLUSION: These findings may serve as a guide to stratify risk in adult HSP patients so that those at higher risk can be monitored more closely.

Risk of Melanoma in Patients with Basal Cell Carcinoma: A Population-based Cohort Study.

Basal cell carcinoma is the most prevalent cancer in Caucasians worldwide. The aim of this study was to examine the overall risk of melanoma among patients diagnosed with basal cell carcinoma. This population-based retrospective cohort study included data from January 2010 to December 2018 from the databases of the Clalit Health Maintenance Organization and 2 major pathology laboratories in North District, Israel. The incidence and hazard ratio of melanoma in patients with a diagnosis of basal cell carcinoma were determined. Of 466,700 participants, 51% were women and the mean (standard deviation) follow-up was 6.7 (2.9; range 1-9) years. A total of 3,338 patients were diagnosed with basal cell carcinoma during the study period, 82 of whom subsequently developed melanoma. Patients with basal cell carcinoma had a significantly higher incidence of melanoma than patients without basal cell carcinoma (2.46% vs 0.37%; p < 0.0001). Univariate Cox regression analysis revealed a hazard ratio of 6.6 (95% confidence interval: 3.6-12.1; p < 0.0001) for melanoma in patients with a diagnosis of basal cell carcinoma. In conclusion, a diagnosis of basal cell carcinoma confers a significant risk of melanoma.

Potential di-genic contribution to guttate leukoderma as the predominant feature of epidermolysis bullosa simplex.

Inherited epidermolysis bullosa (EB) simplex is a heterogeneous group of skin fragility disorders caused by mutations in genes encoding cell-cell or cell-matrix adhesion proteins. A recently identified, rare subtype of EB simplex is due to bi-allelic mutations in the EXPH5 gene, which encodes exophilin5, an effector protein of the Rab27B GTPase involved in intracellular vesicle trafficking and exosome secretion. The EXPH5 EB subtype is characterized by early-onset skin blisters and scars, mainly on extremities, and varying degrees of pigmentary alterations. Here, we present a 31-year-old female with diffuse guttate hypopigmentation on the trunk and extremities since early childhood, with no apparent blisters or scars. We employed whole exome sequencing of germline DNA extracted from the patient's leukocytes to determine the genetic aetiology of the phenotype. A novel homozygous variant in EXPH5, c.1153C>T causing a premature stop codon at amino acid Glutamine 385, was identified. Histologic examination after skin pricking disclosed focal keratinocyte detachment typical to EB. Additionally, we identified a deleterious-predicted variant in ENPP1, a gene associated with disturbed transfer of melanosomes to keratinocytes in Cole disease. Our report expands the clinical spectrum of inherited EB simplex with a possible di-genic synergism contributing to co-presentation with guttate leukoderma.

Acral peeling in Nagashima type palmo-plantar keratosis patients reveals the role of serine protease inhibitor B 7 in keratinocyte adhesion.

Acral peeling skin syndrome (APSS) is a heterogenous group of genodermatoses, manifested by peeling of palmo-plantar skin and occasionally associated with erythema and epidermal thickening. A subset of APSS is caused by mutations in protease inhibitor encoding genes, resulting in unopposed protease activity and desmosomal degradation and/or mis-localization, leading to enhanced epidermal desquamation. We investigated two Arab-Muslim siblings with mild keratoderma and prominent APSS since infancy. Genetic analysis disclosed a homozygous mutation in SERPINB7, c.796C > T, which is the founder mutation in Nagashima type palmo-plantar keratosis (NPPK). Although not previously formally reported, APSS was found in other patients with NPPK. We hypothesized that loss of SERPINB7 function might contribute to the peeling phenotype through impairment of keratinocyte adhesion, similar to other protease inhibitor mutations that cause APSS. Mis-localization of desmosomal components was observed in a patient plantar biopsy compared with a biopsy from an age- and gender-matched healthy control. Silencing of SERPINB7 in normal human epidermal keratinocytes led to increased cell sheet fragmentation upon mechanical stress. Immunostaining showed reduced expression of desmoglein 1 and desmocollin 1. This study shows that in addition to stratum corneum perturbation, loss of SERPINB7 disrupts desmosomal components, which could lead to desquamation, manifested by skin peeling.

Concomitant variants in NF1, LZTR1 and GNAZ genes probably contribute to the aggressiveness of plexiform neurofibroma and warrant treatment with MEK inhibitor.

Neurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. In this study, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two RASopathy-associated genes were identified using whole-exome sequencing-a de novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G protein-coupled receptor. Cells expressing mutant GNAZ exhibited increased ERK 1/2 activation compared to those expressing wild-type GNAZ. Taken together, we suggest the variants in NF1, LZRT1 and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.

Bullous Pemphigoid and Scabies: Is There an Association?

BACKGROUND: Bullous Pemphigoid (BP) is an autoimmune subepithelial bullous disease. Several reports suggested an association between BP and scabies. OBJECTIVE: We aimed to evaluate whether an association between BP and scabies exists. METHODS: This is a retrospective matched case-control study. We retrospectively identified BP patients treated in our clinic between January 1, 2009, and December 31, 2016. Each patient was assigned to 3 control subjects (matched by age and sex) treated in our clinic, not due to BP. The study group was examined for a scabies diagnosis within the 3 years prior to BP diagnosis; the control group was examined for a scabies diagnosis 3 years prior to its first visit in our clinic. RESULTS: Fifteen out of the 87 (17.2%) BP patients were diagnosed with scabies within the 3 years prior to their initial BP diagnosis, compared to only 4.2% (11 out of 261) among the control group. The odds ratio of scabies history was 4 times higher among BP patients compared to the control group (OR=4.23; 95% CI: 1.50–11.91, P=0.007). LIMITATIONS: A retrospective study design. CONCLUSIONS: An association between scabies diagnosis and BP is demonstrated in our study. J Drugs Dermatol. 2022;21(9):1009-1011. doi:10.36849/JDD.4900.

Phototherapy for Generalized Pruritus of Unknown Origin: Single-Center Experience.

OBJECTIVE: Phototherapy is a well-established therapy in dermatology. However, there is limited evidence regarding phototherapy for the treatment of generalized pruritus of unknown origin (GPUO). The objective of this study was to assess the efficacy and safety of narrowband ultraviolet B (NB-UVB) phototherapy in patients with GPUO. METHODS: Researchers conducted a retrospective review of the treatment outcomes of patients with GPUO who were treated with NB-UVB between 2004 and 2019 at their facility. RESULTS: Investigators included 67 patients diagnosed with GPUO treated with NB-UVB. Complete remission was achieved in more than 70% of the patients. No serious adverse events were documented. CONCLUSIONS: For patients with GPUO, NB-UVB may be a safe and effective treatment option.

Interviewing Women with Hidradenitis Suppurativa-Thematic and Content Analysis.

OBJECTIVE: Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disease with a higher prevalence in women. The disease results in a low quality of life as well as physical and psychological comorbidities. The authors sought to determine the effects of HS on women's self-perception and life experiences. METHODS: Semistructured interviews were conducted with 22 women of varying age and family status. The content was transcribed and subjected to both thematic and content analyses. RESULTS: Five themes and a number of subthemes were revealed, involving physical, emotional, coping, and functional aspects. Somatic features, especially pain, were the most troubling issues, along with the emotional burden of shame and loss of femininity and intimacy. However, women also revealed strength and expressed optimism. CONCLUSIONS: These findings reveal the inner world of women coping with HS, addressing multiple dilemmas, problems, and concerns. Healthcare providers should pay special attention to the specific needs of these patients. Additional research is needed to further shed light on the impact of HS on women.

Retrospective Study of Patients With SJS/TEN Treated at a Tertiary Burn Unit in Canada: Overview of 17 Years of Treatment.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are adverse drug reactions. OBJECTIVES: To learn about the clinical characteristics of patients with SJS/TEN including treatments provided, outcomes, and mortality. METHODS: We conducted a retrospective chart review of patients who were hospitalized with the diagnosis of SJS/TEN at the Ross Tilley Burn Center between the years 1999 and 2015. RESULTS: A total of 43 patients were identified with a mean age of 54 ± 19 (58, 18-85). The most common offending medications were allopurinol and carbamazepine. The overall mortality rate in our study is 21% with the most common causes of death being multiorgan failure and sepsis. The majority of our patients had oral (84%), ocular (79%), and genital (60%) involvement during hospitalization. Our data revealed that combination treatment involving oral corticosteroids with intravenous immunoglobulin (IVIG) had the highest mortality rate in our study since 55% (6/11) of patients who were treated in this manner passed away compared to 11% (2/18) of patients passing away who were treated with solely IVIG and 33% (1/3) who were treated with only supportive care. Our study also demonstrates the addition of etanercept and cyclosporine treatment in the second time period we studied: 2008-2015 versus the earlier time period of 1999-2007. None of the patients in our study who were treated with therapies including cyclosporine and/or etanercept passed away. CONCLUSIONS: Our study sheds light on a possible beneficial role of cyclosporine and etanercept for the treatment of SJS and TEN and reinforces the necessity of a multidisciplinary care team for patients.

An Update on the Cutaneous Manifestations of Darier Disease.

BACKGROUND: Knowledge about the clinical features of Darier disease, an orphan autosomal-dominant genetic disorder, is sparse and has been evaluated only in few studies. OBJECTIVES: To investigate the clinical features of a large group of patients with Darier disease, and to explore for associations between disease characteristics and severity of the disease. METHODS: Seventy-six individuals with Darier disease were evaluated utilizing a structured questionnaire-based interview, a physical examination, and a retrospective assessment of their medical records. RESULTS: The most frequent locations of lesions were hands (99%) and fingernails (93%). Wart-like lesions on the hands were more visible after soaking them in water for 5 minutes, we therefore named this phenomenon the "wet hand sign". Oral involvement was found in 43% of patients, while 48% of women and 16% of men showed genital lesions. Patients with severe Darier disease had a tenfold greater risk of developing genital lesions than those with mild disease (P = .01). Most patients (88%) in our study exhibited a combination of the four types of the disease patterns of distribution (flexural, seborrheic, nevoid, and acral). CONCLUSIONS: Documentation of disease on the hands and fingernails provides a highly sensitive means to aid in the diagnosis of Darier disease. It is important to evaluate mucosal lesions including genital and oral mucosa.

[SYSTEMIC REVIEW OF EOSINOPHILIC DERMATOSES PATIENTS TREATED WITH TNF-Α INHIBITORS AND USTEKINUMAB].

AIMS: This study aims to critically review the pros and cons of biological drugs as treatments and triggers of eosinophilic dermatoses. BACKGROUND: Eosinophilic dermatoses syndromes are rare diseases with a prominent eosinophilic infiltration mechanism. These syndromes have several known treatments with limited success. Several physicians worldwide suggested possible advantages of using specific biological drugs, which are different from eosinophil targeted biotherapies as treatments for eosinophilic dermatoses syndromes. Others considered these drugs as possible triggers. METHODS: Articles published in the last 30 years containing relevant key words were reviewed using PubMed and Medline. Associations between Infliximab, Adalimumab, Etanercept, TNF alpha inhibitors and Ustekinumab to Eosinophilic Dermatoses syndromes were reviewed. RESULTS: Our search revealed an association between 17 eosinophilic dermatoses patients and the drugs of interest. Out of 5 Wells' syndrome cases, four patients had an outbreak of the disease following treatment and one improved by the treatment. Six cases of Eosinophilic Fasciitis mostly had a positive reaction to the treatment. More associations were found among 4 cases of Churg-Strauss syndrome, one case of Granuloma Faciale and 1 case of Eosinophilic Pustular Folliculitis. CONCLUSIONS: TNF alpha inhibitors and Ustekinumab may have a role in the treatment of eosinophilic dermatosis syndromes. These drugs may act as triggers among Wells' syndrome patients. Further investigation is needed.

[PIGMENTED BASAL CELL CARCINOMA AND IONIZING RADIATION].

AIMS: This study aimed at demonstrating whether the histological and clinical manifestations of pigmented basal cell carcinoma are different among those who were previously treated with ionizing radiation for ringworm infection. BACKGROUND: Ionizing radiation is known to cause increased morbidity among those who are chronically exposed. Basal cell carcinoma in known to be related to ionizing radiation however, the characteristics of pigmented BCC in relation to ionizing radiation are poorly described. METHODS: The study included the demographics and characteristics of 23 patients with pigmented BCC who were treated for ringworm with ionization radiation and a control group of 21 patients that had not been treated with ionizing radiation. All the cases treated between the years 2005-2015 were included in the study. The data was analyzed with a SPSS program. RESULTS: Among the patients who were treated with ionizing radiation the percentage of the tumors that were well differentiated was 34.8%, much higher than those who were not treated with ionizing radiation - 14.3%. In addition, the average age for those who were treated with ionizing radiation was 66 compared to 73 in the group that weren't treated with radiation. DISCUSSION: Pigmented basal cell carcinoma is a rare variant of BCC and it has characteristics that are quite dissimilar among patients treated with ionizing radiation. However, more studies are needed in order to strengthen the results.

Acetic acid treatment for toe web infection caused by Pseudomonas Aeruginosa combined with fungal infection: A case series of ten patients.

Gram-negative bacterial toe web infection (GNBTWI) caused by Pseudomonas Aeruginosa combined with fungal infection has variety of treatments. However, these treatments have been poorly described in the literature. Our retrospective study describes patients that had been treated in our medical center with acetic acid combined with local antifungal treatment, to evaluate evidences for the appropriateness of this treatment. Ten patients with evidence of GNBTWI caused by Pseudomonas Aeruginosa combined with local fungal infection which have been treated with acetic acid in Emek Medical Center were identified. Eight patients (80%) had a complete response while two patients (20%) showed only a partial response. Side effects were minimal and included temporary stinging sensation. Acetic acid is a relatively cheap ingredient with minimal side effect profile and highly effective outcomes as a treatment for GNBTWI caused by Pseudomonas Aeruginosa and should be considered as an adjuvant treatment.

Thermal acclimation is not induced by habitat-of-origin, maintenance temperature, or acute exposure to low or high temperatures in a pit-building wormlion (Vermileo sp.).

Wormlions are sit-and-wait insect predators that construct pit-traps to capture arthropod prey. They require loose soil and shelter from direct sun, both common in Mediterranean cities, and explaining their high abundance in urban habitats. We studied different aspects of thermal acclimation in wormlions. We compared chill-coma recovery time (CCRT) and heat-shock recovery time (HSRT) of wormlions from urban, semi-urban and natural habitats, expecting those originating from the urban habitat to be more heat tolerant and less cold tolerant. However, no differences were detected among the three habitats. We then examined whether maintenance temperature affects CCRT and HSRT, and expected beneficial acclimation. However, CCRT was unaffected by maintenance temperature, while temperature affected HSRT in an opposite direction to our prediction: wormlions maintained under the higher temperatures took longer to recover. When testing with two successive thermal shocks, wormlions took longer to recover from both cold and heat shock after applying an initial cold shock. We therefore conclude that cold shock inflicts some damage rather than induces acclimation. Finally, both cold- and heat-shocked wormlions constructed smaller pits than wormlions of a control group. Smaller pits probably translate to a lower likelihood of capturing prey and also limit the size of the prey, indicating a concrete cost of thermal shock. In summary, we found no evidence for thermal acclimation related either to the habitat-of-origin or to maintenance temperatures, but, rather, negative effects of unfavorable temperatures.

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study.

BACKGROUND: Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis. OBJECTIVE: To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks. METHODS: Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study. RESULTS: Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% [P < .0001]); PASI 100 responses were 46% versus 36% (P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% (P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index [DLQI], EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab (P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable. LIMITATIONS: There was no placebo arm. CONCLUSION: In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile.

Biologic drug survival in Israeli psoriasis patients.

BACKGROUND: Drug survival is defined as the time period of treatment with a certain drug until its cessation. The role of previous exposure to traditional systemic treatments in biologic survival is still unknown. OBJECTIVE: To investigate the drug survival rates of biologic treatments in patients with psoriasis and to identify predictor factors. METHODS: Survival analysis was performed on patients with severe psoriasis who received adalimumab, infliximab, etanercept, and ustekinumab for treatment of psoriasis, drawn from the Clalit Health Services database. Multivariate analysis was performed adjusting for demographic variables; metabolic syndrome and its components; psoriatic arthritis; biologic naivety; coadministration of methotrexate, acitretin, or cyclosporine; and previous standard systemic treatment exposure. RESULTS: Among 907 patients treated with 1575 biologic treatments, ustekinumab had a significantly higher survival rate than tumor necrosis factor inhibitors. Biologic naivety and concomitant methotrexate intake were positive predictors for drug survival, whereas the female sex and the duration of previous systemic treatments were negative predictors. LIMITATIONS: Data regarding disease severity or duration could not be drawn from the Clalit Health Services database. CONCLUSION: Ustekinumab had better retention rates in comparison with other investigated biologics in patients with severe psoriasis, most of whom used it as a third line therapy.