Correlation of IL36RN and CARD14 mutations with clinical manifestations and laboratory findings in patients with generalised pustular psoriasis

Background: Generalized pustular psoriasis (GPP) is a chronic disease associated with genetic factors related to mutations of the interleukin 36 receptor antagonist gene (IL36RN) and the caspase recruitment domain 14 gene (CARD14). However, the relevance of these mutations to the clinical features and severity of GPP remains unclear. Aims: Our objective was to correlate the presence of IL36RN and CARD14 mutations with the clinical and laboratory findings in patients with GPP. Methods: This cross-sectional descriptive study was conducted in 64 subjects with GPP. Clinical manifestations were recorded and the severity was graded as mild, moderate, or severe. Routine laboratory tests were performed and blood samples were collected for Sanger sequencing. The clinical data of patients were compared among the different mutation groups. Results: The two main variants of IL36RN were c.115+6T > C (p.Arg10ArgfsX1) and c.227C > T (p.Pro76Leu). The major CARD14 mutations were c.2458C > T (p.Arg820Trp), c.1641C > T (p.Arg547Ser), and c.1753G > A transitions. Provocative factors were uncommon in the group with both IL36RN and CARD14 mutations. Drugs (unspecified), especially herbals, were the most common triggers. A history of psoriasis was frequent in patients with only CARD14 mutations, but fever was uncommon. The c.1641C > T mutation was associated with leukocytosis > 15000/mm3 and the c.1753G > A mutation was associated with hypoalbuminemia <3.8g/dL. Both the c.115+6T > C and c.227C > T variants of IL36RN were associated with fever ?38.5°C while the c.115+6T > C variant was also associated with geographic tongue. No gene mutations were associated with the total severity and severity grades. Limitations: Four patients without the two major IL36RN mutations were excluded from the study. Conclusion: The presence of IL36RN and CARD14 mutations were associated with a history of psoriasis, various provocative factors, fever, leukocytosis, hypoalbuminemia, and geographic tongue. Further studies to explore the role of these mutations in therapeutic efficacy and disease outcomes are necessary.

Interleukin-17 and interleukin-23 inhibitors in the treatment of pustular psoriasis / 中华皮肤科杂志

Pustular psoriasis is a serious life-threatening disease, and patients usually show poor response to traditional treatments. In recent years, interleukin-17 and interleukin-23 inhibitors have shown favorable efficacy in the treatment of psoriasis. This review summarizes the latest progress in interleukin-17 and interleukin-23 inhibitors for the treatment of pustular psoriasis.

Generalised Pustular Psoriasis Masquerading as Lepromatous Leprosy: A Case Report

The relationship between psoriasis and leprosy is debatable since ages. The varied clinical manifestations of leprosy may resemble other skin diseases, but there is no documented literature of skin lesions of psoriasis mimicking leprosy. We report a case of generalised pustular psoriasis (GPP) presented with the lepromatous leprosy like clinical features in a 60 year old male. The histopathological examination confirmed the diagnosis. Patient was then treated with Methotrexate 7.5mg weekly and showed improvement in subsequent visits. We report this rare possibility to raise awareness among clinicians to allow accurate diagnosis since leprosy still carries stigma in society

Adalimumab combined with acitretin in the treatment of five children with generalized pustular psoriasis: a retrospective clinical observation / 中华皮肤科杂志

Objective:To evaluate the clinical efficacy and safety of adalimumab combined with acitretin in the treatment of childhood generalized pustular psoriasis.Methods:Five children with generalized pustular psoriasis were collected from Department of Dermatology, Tianjin Children′s Hospital from October 2019 to August 2020. After admission, the patients received oral acitretin at a dose of 0.5 mg·kg -1·d -1. After relevant laboratory examinations, these patients additionally received subcutaneous injections of 20- or 40-mg adalimumab at weeks 0 (the initial dose) , 1, and every 2 weeks thereafter; when patients obtained a 50% improvement in the Japanese Dermatology Association (JDA) severity index score, the dose of acitretin would be reduced to 0.3 mg·kg -1·d -1, and acitretin would be discontinued after a 75% improvement. The disease condition was evaluated at weeks 0, 1, 2, 4, 8, 12 and 24 after the start of adalimumab treatment, and adverse reactions were monitored during treatment. Results:All the 5 patients received drug treatment for at least 40 weeks. After 2-week treatment, 3 patients achieved a 50% reduction in JDA severity index score (JDA50) ; after 4-week treatment, 4 achieved JDA75, and 1 achieved JDA100; after 8-week treatment, all the 5 patients achieved JDA100. By June 2021, all the 5 children received follow-up for at least 40 weeks, no recurrence was observed during the treatment period, and no infections, malignant tumors or other serious adverse reactions occurred.Conclusion:Adalimumab combined with acitretin shows rapid onset of action and high safety in the treatment of childhood generalized pustular psoriasis.

Impetigo herpetiformis in a 33-year-old Filipino female

@#Introduction: Impetigo herpetiformis is a rare pustular disorder that affects pregnant women. It is also otherwise termed as “pustular psoriasis of pregnancy”, owing to the fact that the pustules are sterile and are not associated with a viral etiology. The classic lesions are erythematous patches or plaques with margins studded with subcorneal pustules spreading centrifugally. A cardinal feature of this disorder is the rapid resolution of lesions after delivery. Case Summary: This is a case report of a 33-year-old female, gravida 3, para 2 (2-0-0-2) at 36 weeks age of gestation who presented with one week history of multiple well defined irregularly shaped erythematous annular patches and plaques with marginal pustules on the trunk and extremities. The lesions began on the trunk spreading centrifugally, sparing the face, palms, soles and mucus membrane. Biopsy showed scale crust in the stratum corneum, the epidermis showed acanthosis, spongiosis and neutrophilic microabscesses with focal vacuolar alteration and small sub-epidermal nests on the basal cell layer. The dermis revealed dilated blood vessels and mild superficial perivascular lymphocytic infiltrates. Patient was given Prednisone and Cetirizine with noted resolution of lesions. Conclusion: Recurrences of impetigo herpetiformis in subsequent pregnancies are common with earlier onset in gestation and are characteristically more severe. The complications are placental insufficiency, stillbirth or neonatal death. Early detection is of utmost importance. Management must be multidisciplinary involving a dermatologist, obstetrician and pediatrician.

A Case of Exfoliative Dermatitis Induced by Phototherapy Secondary to Pustular Psoriasis / 대한피부과학회지

No abstract available.

Clinical and Histopathological Study of Generalized Pustular Psoriasis and Subcorneal Pustular Dermatosis Diagnosed at a Tertiary Hospital in Korea / 대한피부과학회지

BACKGROUND: Generalized pustular psoriasis (GPP) and subcorneal pustular dermatosis (SPD) are clinically and histopathologically difficult to distinguish. There have been no comparative studies examining these two diseases in Korea. OBJECTIVE: To investigate the clinical and histopathological characteristics of GPP and SPD. METHODS: We evaluated the clinical features, laboratory, and histopathological findings in 16 patients with generalized pustular eruption who had visited our hospital over the past 10 years and reviewed the literature. RESULTS: Ten GPP and six SPD patients were included in the study. The mean age at diagnosis was 44.4 years in the GPP group and 50 years in the SPD group. The number of patients with previous personal history of psoriasis vulgaris was 2 (20%) for GPP and 0 (0%) for SPD. The number of patients with history of recent exposure to medications was 1 (10%) and 0 (0%) in the GPP and SPD groups, respectively. Symptoms of fever, arthralgia, and mucosal involvement were reported in 10%, 20%, and 10% of GPP patients and 16.7%, 16.7%, and 0% of SPD patients, respectively. Leukocytosis, eosinophilia, elevated ESR/CRP, and elevated AST/ALT were reported in 25%, 0%, 25%, and 50% of GPP patients and in 20%, 0%, 40%, and 40% of SPD patients, respectively. On histological findings, in the GPP group, spongiosis, and psoriasiform changes including hyperkeratosis/parakeratosis, and rete ridge changes were more apparent than in the SPD group. The mean period of clinical improvement was 32.9 days with 40% recurrence in the GPP group and 38.3 days with 66.7% recurrence in the SPD group. CONCLUSION: Although GPP and SPD exhibit clinical and laboratory findings that are similar and difficult to differentiate, systematic analyses including clinical course, laboratory findings, and histopathological findings are helpful for an accurate differential diagnosis.

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 bysudden onset of numerous, non-follicular, sterile pustuleson oedematous erythematous skin, accompanied by feverand neutrophilia. AGEP is predominantly drug-induced. Skinlesions appear rapidly within 1-3 days of drug exposure andupon drug withdrawal, resolve rapidly within 15 days.Objective: To determine the clinical characteristics, culpritdrugs and outcome of patients with AGEP.Methods: A retrospective note review of all AGEP patientsseen from 2001-2015.Results: Among 21 AGEP patients, 76% were Malays, 9.5%Chinese, 9.5% Indians, and 5% Iban. Sixteen were femalesand 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 herbalproduct. The median time from drug initiation to onset ofAGEP was 3 days (IQR: 5.5). Fever was documented in 52.4%, mucosal involvement 9.5%, purpura 4.7% and blisters4.7%. Neutrophilia was observed in 63.6% of patients andeosinophilia in 28.5%. While most patients requiredadmission (67%), all achieved complete recovery within 15days without any sequela.

Annular pustular psoriasis in a 6-year-old child: Case report

@#Annular pustular psoriasis (APP) is a rare variant of pustular psoriasis occurring only in about 1-5.4% of children with psoriasis. Pustular psoriasis is triggered by endogenous and exogenous factors. Exogenous factors include stress, upper respiratory tract infection and withdrawal of systemic corticosteroids. This condition usually requires systemic treatment. However, there are still no randomized controlled trials or standardized guidelines proving the advantage of any specific treatment modality over the other. We report a case of a 6-year-old male who presented with diarrhea followed by appearance of erythematous annular plaques with pustules and nail changes. Punch biopsy showed pustular psoriasis. Patient was treated with topical betamethasone valerate and calcipotriol, and there was noted to have no recurrence of skin lesions for 4 months.

Association of tumor necrosis factor-α gene promoter polymorphisms with generalized pustular psoriasis / 中华皮肤科杂志

Objective To investigate the association of tumor necrosis factor-ot (TNF-α) gene promoter polymorphisms with generalized pustular psoriasis.Methods Totally,91 patients of Han nationality with generalized pustular psoriasis (generalized pustular psoriasis group) and 102 health checkup examinees (healthy control group) were enrolled into this study.PCR and direct sequencing were performed to analyze the-238,-308 and-857 polymorphic sites of the TNF-α promoter.Results The frequency of the A allele at TNF-α-238 site was significantly higher in the generalized pustular psoriasis group than in the healthy control group (P =0.003,OR =4.819,95％ CI:1.581-14.694),so was the frequency of GA/AA genotype (P =0.006,OR =4.455,95％ CI:1.410-14.077).However,no significant differences were observed in the frequencies of G/A alleles (P =0.794) and GG/GA/AA genotypes (P =0.786) at TNF-o-308 site,or in the frequencies of C/T alleles (P =0.474) and CC/CT/TT genotypes (P =0.453) at TNF-α-857 site,between the generalized pustular psoriasis group and healthy control group.Conclusion TNF-α-238G ＞ A polymorphisms may be associated with the occur-rence of generalized pustular psoriasis.

Generalized Pustular Psoriasis

Generalized Pustular Psoriasis (GPP) is a dermatological emergency that often requires hospitalizationbecause of possible life-threatening complications, including heart failure, renal failure and sepsis. Itis a chronic recalcitrant disease in which acute pustular flares frequently recur on exposure to classictriggers. This review article is aimed to update the new insights into the genetic basis of GPP andhighlighted the central role IL1 and IL36 in the pathogenesis of GPP.

AGEP sistémico, un diagnóstico oculto en una falsa psoriasis paradójica por anti-TNF / Systemic AGEP, a hidden diagnosis in a false psoriasis paradoxical by anti-TNF

La pustulosis exantemática generalizada aguda (AGEP, en inglés) es una enfermedad poco frecuente, causada por drogas, caracterizada por aparición aguda de numerosas pústulas estériles en una base eritematosa, asociada en ocasiones a fiebre y leucocitosis, en algunos casos puede causar un compromiso de piel severo pero que resuelve rápidamente con la suspensión del fármaco sin tratamiento especial requerido. Puede confundirse con otras entidades como la psoriasis pustular e inusualmente produce compromiso sistémico. Presentamos un caso de AGEP secundario a terapia anti-TNF con compromiso sistémico.

The acute generalized exanthematous pustulosis (AGEP, in english)is a rare disease caused by drugs, characterized by acute onsetof numerous sterile pustules on an erythematous base, sometimesassociated with fever and leukocytosis, in some cases may causea severe skin involvement reaction but solved quickly with the drugsuspension without special treatment required. It can be confusedwith other entities such as pustular psoriasis and unusually producesystemic involvement. We present a case of secondary to anti-TNFtherapy AGEP systemic involvement.

A Case of Subcorneal Pustular Dermatosis / 대한피부과학회지

No abstract available.

Early Onset Generalized Pustular Psoriasis Accompanying IL36 Receptor Antagonist (IL36RN) Gene Mutation in a 14-year-old Korean Male Patient with No Family History / 대한피부과학회지

No abstract available.

A Case of Peripheral Ulcerative Keratitis and Scleritis in a Patient with Pustular Psoriasis

PURPOSE: To report a case of peripheral ulcerative keratitis and scleritis in a patient with pustular psoriasis. CASE SUMMARY: A 62-year-old male presented with skin lesions on the hands and feet and pain in the right eye, which started a few days prior. Corrected visual acuity was 0.5 in the right eye and 0.7 in the left eye at initial visit. Corneal edema, erosion, ulcer and peripheral corneal infiltration of the right eye were observed. However, anterior chamber reaction was not observed. Histological analysis of hand skin lesions indicated pustular psoriasis. The patient was initially treated with topical antibiotics and a combined therapy of oral and topical steroids for ocular symptoms. As a result, the right eye showed slight improvement and the oral steroid was discontinued. One month after the initial visit, scleritis appeared on the left eye and topical and oral steroids were restarted for both eyes. Two months after the initial visit, ocular symptoms were improved significantly and corrected visual acuity was 1.0 in both eyes. The mild peripheral corneal opacity remained in the right eye, but the previous inflammations in both eyes were improved. CONCLUSIONS: As shown in this case, possibility of peripheral corneal infiltration, corneal ulcer and scleritis should be considered in patients with pustular psoriasis and topical and systemic steroids should be administered if accompanying ocular manifestations occur.

Acrodermatitis continua de Hallopeau: reporte de un caso / Acrodermatitis continua of Hallopeau: case report

La acrodermatitis continua de Hallopeau (ACH) es una enfermedad inflamatoria crónica que afecta a los dedos de las manos y/o pies, se caracteriza por una placa eritematodescamativa con erupciones pustulosas estériles. Es una patología rara o quizá subdiagnosticada y más frecuente en mujeres de edad mediana, según los pocos casos reportados. Se presenta el siguiente caso clínico de una adolescente de 15 años de edad, que presentó una placa eritematodescamativa con pústulas estériles, en tres oportunidades a lo largo de dos años. El diagnóstico de ACH se realizó por la clínica y la histología. Se indicó tratamiento con acitretina vía oral y se tiene mejoría clínica importante.

The acrodermatitis continua of Hallopeau (ACH) is a chronic inflammatory disease that affects the fingers and toes, is characterized by erythematous scaly plaque with sterile pustular eruptions. It is a rare condition or perhaps underdiagnosed, according the few reported cases is more common in middle aged women. We report the case of a 15 year-old woman which presented an erythematous plaque with sterile pustules on three occasions along two years, the diagnosis of ACH was made by clinical and histology. Acitretin therapy is indicated orally and has significant clinical improvement.

A Case of Acrodermatitis Continua of Hallopeau Treated with Etanercept / 대한피부과학회지

Acrodermatitis continua of Hallopeau (ACH) is a rare form of acropustular eruption characterized by a presence of aseptic pustules on inflammatory periungual or subungual regions. Frequently accompanied by paronychia, atrophic skin changes, onychodystrophy, and osteolysis of distal phalanges of the digits, it is considered to be a variant of pustular psoriasis with a chronic relapsing course and refractoriness to many therapeutic modalities. Here, we present a case of a 45-year-old female who presented with multiple pustules pathologically diagnosed as pustular psoriasis on her left thumb. She suffered from ACH for over a decade, and in the process experienced frequent relapses and showed poor response to numerous treatment modalities such as narrow band UVB, topical steroid, steroid intralesional injection, oral retinoids, 308 nm excimer laser, and oral immune suppressants. However, the patient showed dramatic clinical improvements to administration of etanercept (TNF-alpha antagonist, twice a week) for a period of one month. The cessation of etanercept led to recurrence of symptoms and marked deterioration of the skin lesion within a month again, but the re-initiation of treatment soon relieved the problem. After completion of a three months trial of etanercept, the cutaneous lesion subsided, and the patient is now successfully controlled with topical steroid maintenance therapy. Hereby, we report a patient with ACH successfully treated with etanercept.

A Case of Pustular Psoriasis Developed during Infliximab Treatment for Crohn's Disease / 대한피부과학회지

Infliximab is a monoclonal antibody that binds and inactivates tumor necrosis factor-alpha. It has been successfully used to manage diseases associated with a Th1 profile such as psoriasis, Crohn's disease, and rheumatoid arthritis. A 15-year-old boy presented for erythematous scaly papules and pustules with crust on his entire body, which had appeared initially 2 months ago. He had been treated with infliximab for Crohn's disease during the last 14 months and had not been diagnosed with psoriasis. A skin biopsy specimen demonstrated papulosquamous dermatitis with subcorneal pustule formation, suggestive of pustular psoriasis. The patient was treated with oral retinoid 20 mg/d for 3 weeks and 10 mg/d for next 3 weeks with concurrent topical steroid, and most lesions disappeared completely with post inflammatory hyperpigmentation. No evidence of recurrence has been observed during 3 months of followup.

A Case of Interstitial Pneumonitis Induced by Acitretin / 대한내과학회지

Retinoids are effective systemic agents in the treatment of psoriasis. Acitretin, a synthetic aromatic derivative of retinoic acid, has replaced etretinate in retinoid therapy of psoriasis because of its more favorable pharmacokinetic profile, including a significantly shorter half-life. Most of the adverse effects associated with acitretin are teratogenicity, hepatotoxicity, pseudotumor cerebri, pancreatitis, hyperlipidemia, hyperostosis, and mucocutaneous side effects. There are two reports worldwide describing patients who developed acute respiratory distress syndrome associated with acitretin. This suggests the possibility of serious lung complications associated with acitretin. We report a case of a 61-year-old man who developed interstitial pneumonitis that might have been induced by acitretin during the treatment of pustular psoriasis. In these cases, immediate withdrawal of retinoic acid is necessary, and corticosteroid therapy should be considered.

A Case of Tumor Necrosis Factor-alpha Inhibitors-induced Pustular Psoriasis

Anti-tumor necrosis factor (TNF)-alpha agents promise better disease control for the treatment of ankylosing spondylitis resistant to classical disease-modifying treatments. Etanercept, a recombinant human TNF receptor fusion protein, is used to treat a variety of TNF-alpha-mediated diseases by inhibiting the biological activity of TNF-alpha. We experienced a case of pustular psoriasis in a 32-year-old man during anti-TNF-alpha therapy with etanercept. He had a history of ankylosing spondylitis for 2 years. Two years after treatment of etanercept, erythematous pustules developed on his palms and soles. He had no previous history of pustular psoriasis. The skin lesion improved as the etanercept therapy was stopped, but pustular skin eruption recurred as adalimumab, a different TNF-alpha inhibitor, was administered to manage his ankylosing spondylitis. Several TNF-alpha inhibitors have different molecular structures, but these inhibitors might have a similar potency to induce pustular psoriasis from this case.