Health-related quality of life in patients with generalized pustular psoriasis: A systematic literature review.

Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.

Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study.

Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.

A retrospective study on drug survival of biologic among patients with psoriasis seen in tertiary hospital in Johor Malaysia.

INTRODUCTION: Limited information exists regarding drug survival of biologics among psoriasis patients in Malaysia. This study aimed to determine the drug survival of biologics in Malaysian psoriasis patients, the reasons for drug discontinuation and to identify the predictor of drug survival. MATERIALS AND METHODS: A retrospective review of case notes on adult psoriasis patients treated with biologics in Hospital Sultanah Aminah Johor Bahru Malaysia, between January 2006 and December 2020. Drug survival was analysed using the Kaplan-Meier method. RESULTS: By December 2020, 100 patients with 154 treatment courses of biologics were included in the study. Male to female ratio was 1:1. The mean age at onset was 31.36 ± 11.72 years. Ustekinumab was the most frequently prescribed biologics (39%), followed by adalimumab (29.2%), secukinumab (14.9%), etanercept (13%), and infliximab (3.2%). Overall median drug survival for biologics was 25 months (interquartile range [IQR]= 12.0-.0). The median drug survival for ustekinumab was 35 months (IQR, 12-93); followed by 25 months (IQR, 12.0-), 18 months (IQR, 7-85), 17 months (IQR, 11-43), and 8 months (IQR, 1-10) for secukinumab, adalimumab, etanercept, and infliximab, respectively. The main reason for drug discontinuation was loss of efficacy (26%), inadequate funding (14.3%), loss to follow-up (10.4%), adverse events (4.5%), and patients' request (1.3%). CONCLUSION: Our study shows ustekinumab has the best long-term drug survival among biologics in Malaysian patients with psoriasis in real-life setting. Further study is required to evaluate the long-term drug survival for newer biologics.

Serum 25-Hydroxyvitamin D deficiency in Malaysian children with severe atopic dermatitis.

BACKGROUND: Vitamin D deficiency has been shown to be a determinant of disease severity in patients with atopic dermatitis (AD). There is a lack of information on the prevalence of vitamin D deficiency in Malaysian children with AD. The objective of this study was to determine the association of vitamin D deficiency with AD severity, to compare vitamin D deficiency between children with and without AD and to determine prevalence of vitamin D deficiency in children with AD. METHODS: A case-control study to examine serum 25- hydroxyvitamin D [25(OH)D] levels in children with and without AD was done. Serum 25-hydroxyvitamin D [25(OH)D] level was measured by immunoassay. AD severity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index. RESULTS: The serum levels of 25(OH)D, measured in 135 children with AD was not statistically different from 65 children without AD [median (IQR): 25.2ng/mL (15.45) vs 25.9ng/mL (15.87), p=0.616]. However, serum vitamin D levels were significantly lower in children with severe AD compared to those with mild-to-moderate AD [median (IQR): 16.0ng/mL (19.32) vs 26.3ng/mL (15.56), p=0.021]. The odds of having vitamin D deficiency in children with severe AD was 3.82 times that of children with non-severe AD (95% confidence level: 1.13, 12.87). CONCLUSION: This study suggests that there is an inverse association between vitamin D level and the severity of AD in Malaysian children.

Clinical characteristics, culprit drugs and outcome of patients with Acute Generalised Exanthematous Pustulosis seen in Hospital Sultanah Aminah, Johor Bahru.

BACKGROUND: Acute generalised exanthematous pustulosis (AGEP) is a rare, cutaneous reaction characterised by sudden onset of numerous, non-follicular, sterile pustules on oedematous erythematous skin, accompanied by fever and neutrophilia. AGEP is predominantly drug-induced. Skin lesions appear rapidly within 1-3 days of drug exposure and upon drug withdrawal, resolve rapidly within 15 days. OBJECTIVE: To determine the clinical characteristics, culprit drugs and outcome of patients with AGEP. METHODS: A retrospective note review of all AGEP patients seen from 2001-2015. RESULTS: Among 21 AGEP patients, 76% were Malays, 9.5% Chinese, 9.5% Indians, and 5% Iban. Sixteen were females and 5 were males. Median age of patients was 40 years (IQR: 26). The main culprit drug was amoxicillin (10 cases), followed by cloxacillin (three cases), phenytoin (two cases) and one case each of carbamazepine, sulphasalazine, allopurinol, cephalexin, ceftriaxone, celecoxib and herbal product. The median time from drug initiation to onset of AGEP was 3 days (IQR: 5.5). Fever was documented in 52.4 %, mucosal involvement 9.5%, purpura 4.7% and blisters 4.7%. Neutrophilia was observed in 63.6% of patients and eosinophilia in 28.5%. While most patients required admission (67%), all achieved complete recovery within 15 days without any sequela. CONCLUSIONS: AGEP predominantly affects Malay females in this study. The most common culprit drug was amoxicillin. Our patients exhibited the classic clinical manifestations of AGEP and confirmed the generally benign nature of this reaction upon drug withdrawal. Although the overall prognosis is good, prompt diagnosis of AGEP is important because drug withdrawal is the mainstay therapy.

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Incidence of cutaneous adverse drug reactions among medical inpatients of Sultanah Aminah Hospital Johor Bahru.

INTRODUCTION: Cutaneous adverse drug reactions (cADRs) are common. There are only few studies on the incidence of cADRs in Malaysia. OBJECTIVE: To determine the incidence, clinical features and risk factors of cADRs among hospitalized patients. METHODS: A prospective study was conducted among medical inpatients from July to December 2014. RESULTS: A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction. CONCLUSION: The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.

Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population.

Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.

Clinical features and prognostic factors of cutaneous vasculitis among dermatology patients in Johor Bahru, Malaysia.

BACKGROUND: Cutaneous vasculitis is common, yet the risk factors for its chronicity have not been established. OBJECTIVE: To describe the clinical spectrum and identify risk factors for chronicity of cutaneous vasculitis. METHODS: Retrospective data analysis of 275 patients diagnosed with cutaneous vasculitis from January 2008 to December 2013. RESULTS: The mean age was 33.7 (±17.89) years, with female predominance. The majority of patients were Malays (67.3%). Skin biopsy was performed in 110 (40%) patients. The commonest sign was palpable purpura (30.6%). The aetiology remained elusive in 51.3% of patients. Common identifiable causes include infection (19.7%) and connective tissue disease (10.2%). Extracutaneous features were noted in 46.5% of patients. Erythrocyte sedimentation rate and antinuclear antibody were raised in 124 of 170 and 27 of 175 patients with documented results respectively. Cutaneous vasculitis was the presenting symptom in seven patients with newly diagnosed systemic lupus erythematosus. Anti Streptolysin O Titre was positive in 82 of 156 patients with documented results. Despite antibiotics, 31.7% of them had chronic lesions. Prednisolone alone was used in 20% of patients while 16.4% needed steroid-sparing agents. Most patients who needed systemic therapy (62%) had unidentifiable aetiology. Among the 155 patients who remained under follow up, 36.4% had chronic disease, one patient succumbed due to septicaemia, and the rest fully recovered within three months. The presence of ulcerative lesion was significantly associated with developing chronic vasculitis (p=0.003). CONCLUSION: The clinical spectrum of cutaneous vasculitis in our population was similar to other studies. Ulcerative lesion predicts a chronic outcome.

Clinico-epidemiological profile, including body mass index of Malaysian children with psoriasis.

BACKGROUND: Limited information exists regarding paediatric psoriasis and its association with body mass index (bMI) in Asia. OBJECTIVES: to determine the clinico-epidemiological profile and to compare the bMI of children with and without psoriasis. METHODS: A case-control study of 92 children with psoriasis versus 59 with atopic eczema and 56 with non-inflammatory skin conditions. RESULTS: Psoriasis was more common in Malay and Indian children when compared to Chinese with odds ratios (Or) of 4.30 (95% CI, 1.85-9.99) and 3.00 (95% CI, 1.02-8.81) respectively. Prevalence of psoriasis was similar between Malay and Indian children (Or 1.43, 95% CI, 0.63-3.25). Male:female ratio was 1:1.09. the mean onset age of psoriasis was 7.9 years. Median onset age was earlier in males (6.5 years versus 9.0 years in females, p=0.05). Plaque psoriasis was the most common phenotype (89.1%) and 94.5% had scalp lesions. Arthritis was seen in 4.3%. Odds of excess adiposity, defined as bMI ≤85th percentile, was higher in children with psoriasis versus noninflammatory controls (Or 2.35, 95% CI 0.99-5.56, p= 0.052). No increased risk of adiposity was noted between children with psoriasis and eczema (Or 1.14, 95% CI 0.5-2.62, p=0.753). More children with psoriasis (17.4%) and eczema (20.3%) were underweight (bMI <5th percentile) compared to non-inflammatory controls (10.7%). CONCLUSION: Malays and Indians are three to four times more likely than Chinese to have psoriasis in multi-ethnic Malaysia. Plaque psoriasis is the most common phenotype. Odds of excess adiposity is about two times higher in children with psoriasis compared to non-inflammatory controls although this observation just missed conventional statistical significance.

Demographic characteristics and prevalence of other sexually transmitted diseases in HIV-positive patients seen in the Dermatology cum Genitourinary Clinic, Hospital Sultanah Aminah, Johor Bahru.

The demographic characteristics, risk behaviourand prevalence of other sexually transmitted diseases (STDs) were determined in 132 HIV-infected individuals seen in a Dermatology cum Genitourinary Clinic, Hospital Sultanah Aminah Johor Bahru. Sixty-one (46.2%) were Malays, 37.9% Chinese, 10.6% Indians and 5.3% were of other ethnic groups. The male to female ratio was 4.5:1. Most of the patients (82.5%) were between 20 to 40 years-old. Seventy (53.0%) were single, 34.1% were married and 7.5% were divorcees. The majority of them (97.7%) were heterosexual. Fifty seven (53.3%) of our male patients patronised commercial workers. Eighty-one (61.8%) were not intravenous drug users (IVDU). Of the 50 IVDUs, 24 had multiple sexual exposures. Fifty-three (48.2%) of the 109 patients screened for STDs had one or more other STDs. Thirty-four patients (31.9%) reported one STD in the past and 3.6% reported two STDs in the past. Fifty-six patients (42.4%) had developed AIDS. Thirteen had passed away. The main mode of transmission of HIV infection in this population is through heterosexual intercourse and the prevalence of STDs is high. These findings indicate a need to advocate responsible sexual behaviour and to detect as well as treat STDs early to prevent the sexual transmission of HIV.

Sexual behaviour and HIV knowledge among Dermatology cum Genitourinary Clinic attendees, Johor Bahru, Malaysia.

A study was conducted in the Dermatology cum Genitourinary Clinic, Hospital Sultanah Aminah Johor Bahru to determine a local population's knowledge of HIV and their sexual behaviour in relation to it. A total of 231 men and 217 women were interviewed. The sexual culture seen is one of relatively late age of first sexual intercourse, low level of partner change and low level of condom use. Men reported a higher involvement in risk behaviour. Nearly all the respondents (95.8%) have heard of HIV/AIDS but had incorrect perceptions of its mode of transmission and its associations with risk groups. This study enable us to gain background information about our patients sexual behaviour and HIV knowledge. There is a need to continue HIV education to improve our public's HIV knowledge and the results of this study provides a baseline against which future educational interventions can be gauged.

A report of two non-AIDS associated Kaposi's sarcoma in Malaysia.

Kaposi's sarcoma is an uncommon cutaneous neoplasm seen classically in elderly males of East European or Jewish extract. It has been known to be endemic in sub-Saharan Africa for many years. Numerous cases had been described in patients on long-term immunosuppressive therapy and in patients living with acquired immunodeficiency syndrome (AIDS). In spite of the increasing number of organ transplant recipients and people living with AIDS. Kaposi's sarcoma remains rare in Asia. We report two cases seen in Johor, Malaysia.