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.

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.

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.

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.

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.

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.

Generalized Pustular Psoriasis of Pregnancy Treated with Systemic Steroid and Narrowband UVB / 대한피부과학회지

Generalized pustular psoriasis of pregnancy (GPPP) is a rare form of pustular psoriasis that occurs in pregnant women during the third trimester. It is characterized by erythematous plaques, peripheral scale and sterile pustules, and this malady is associated with systemic symptoms such as fever, malaise, diarrhea and pain. A 34-year-old primigravida woman with an intermittent history of plaque psoriasis for 12 years presented with a two week history of increasingly widespread erythematous eruptions and associated peripheral pustules. The histopathologic findings were consistent with pustular psoriasis. She was diagnosed with generalized pustular psoriasis of pregnancy and she was treated with systemic and topical steroid, narrowband ultraviolet B phototherapy and wet dressings. 2 weeks after treatment, the patient demonstrated clinical and symptomatic improvement.

Generalized Pustular Psoriasis and Hepatic Dysfunction Associated with Oral Terbinafine Therapy

We report a case of 61-yr-old man with stable psoriasis who progressively developed generalized pustular eruption, erythroderma, fever, and hepatic dysfunction following oral terbinafine. Skin biopsy was compatible with pustular psoriasis. After discontinuation of terbinafine and initiating topical corticosteroid and calcipotriol combination with narrow band ultraviolet B therapy, patient's condition slowly improved until complete remission was reached 2 weeks later. The diagnosis of generalized pustular psoriasis (GPP) induced by oral terbinafine was made. To our knowledge, this is the first report of GPP accompanied by hepatic dysfunction associated with oral terbinafine therapy.

A Case of Generalized Pustular Psoriasis Associated with Systemic Lupus Erythematosus / 대한피부과학회지

Generalized pustular psoriasis (GPP) is an acute, systemic form of psoriasis, characterized by fever, chills, rigors, and generalized pustule formation on the skin. The concomitant occurrence of lupus erythematosus and psoriasis has been reported sporadically. But the coexistence of GPP and systemic lupus erythematosus have rarely occurred. We herein report a case of GPP in a 19-year-old female, who has been managed with SLE since the age of 14 years.

A Case of Generalized Pustular Psoriasis Associated with Myasthenia Gravis / 대한피부과학회지

Generalized pustular psoriasis(GPP) is an uncommon and severe form of psoriasis. The possible provocative factors such as steroid therapy, infection, stress, drugs, pregnancy, sun exposure, and metabolic disorders were reported. Among them, corticosteroid therapy is thought to be the most common factor. Although the cause of psoriasis remain obscure, the coexistence of psoriasis and autoimmune disease and cyclosporin accepted for the treament of psoriasis emphasize the importance of immunologic mechanism in the pathogenesis of psoriasis. We present a case of GPP in a 48-year-old male, who has had a history of myasthenia gravis since the age of 34 years and managed with long-term corticosteroid therapy. With the administration of acitretin and cyclosporin, generalized pustular eruptions nearly cleared and clinical improvement was achieved.

Two Cases of Generalized Pustular Psoriasis Improved with Combination Treatment of Mycophenolate Mofetil / 대한피부과학회지

Mycophenolate mofetil(MMF) is a new immunosuppressant which non-competitively and reversibly blocks the de novo synthesis of guanine nucleotides required for DNA and RNA synthesis during lymphocyte proliferation. So MMF selectively inhibits lymphocyte proliferation and it has less side-effects than other immunosuppressants. We described 2 cases of generalized pustular psoriasis improved with MMF. We administered MMF combined with cyclosporin in case 1 and acitretin in case 2. Both patients markedly improved with MMF administration 3 days after and had no severe side-effects. Thus the authors thought that MMF appears to be an effective therapeutic alternative in the treatment of generalized pustular psoriasis.

A Case of Generalized Pustular Psoriasis Improved with Isotretinoin / 대한피부과학회지

Generalized pustular psoriasis is a lethal variant of psoriasis characterized by the appearance of sterile pustules on psoriatic skin. Etretinate and acitretin are effective in pustular forms of psoriasis, including generalized pustular psoriasis. A major concern with the use of systemic retinoid is their high teratogenic potential. Since etretinate and acitretin are remetabolized into long-lived compounds, isotretinoin may be used to treat women of childbearing years with generalized pustular psoriasis. We report a case of generalized pustular psoriasis in a 28-year-old woman whose condition was improved with isotretinoin. Clinical improvement was noted with the administration of isotretinoin at the dose of 30mg/day.

A Case of Annular Pustular Psoriasis Showing Features of Subcorneal Pustular Dermatosis / 대한피부과학회지

Annular pustular psoriasis(APP) is a rare variant of the generalized pustular psoriasis characterized by subacute onset of annular lesion with peripheral advancing pustules. Histologically, it is characterized by spongiform and/or subcorneal pustules which are also found in subcorneal pustular dermatosis(SPD). SPD is very difficult to differentiate from APP, although SPD is thought to be a separate and distinctive entity because of its clinical appearance, characteristic histology, and response to dapsone. We herein report a case of APP showing clinical and histologic features of SPD developed in a patient who had a history of generalized pustular psoriasis.

Clinicopathologic Study of Generalized Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis / 대한피부과학회지

BACKGROUND: Generalized sterile pustular eruption with fever which occurs in generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis(AGEP) present a diagnostic and therapeutic problems. In Korea, there are a few studies of clinical and histopathologic reviews of these diseases, but long term follow-up and comparative clinicopathologic studies of these two diseases are not available. OBJECTIVE: This study attempts to identify the differences of these two diseases in the aspects of clinical, laboratory, and histopathologic findings. METHODS: We evaluated the clinical features, laboratory and histopathologic findings in 41 patients with generalized pustular eruption who had visited Pusan National University hospital during the past 20 years and reviewed the literature. RESULTS: 1. The ratio of patients with GPP(n=32) to ones with AGEP(n=9) was 3.6:1. 2. The mean age at diagnosis was 32.9(male) and 28.9(female) years in GPP, and 10.3 years(male) and 62.8 years(female) in AGEP. 3. The number of patients of GPP with previous personal history of psoriasis vulgaris were 15/32(46.9%) and the number of ones with previous family history of psoriasis vulgaris were 2/32(6.3%). 4. There was no patient of AGEP with personal or familial history of psoriasis. 5. The number of patients with recent drug intake history were 4/32(12.9%) in GPP and 9/9(100%) in AGEP. And common drugs suspected to cause AGEP were antibiotics(4 cases) and analgesics(3 cases). 6. Associated systemic symptoms were fever(37.5%), arthralgia(18.8%), and itching(62.5%) in GPP, whereas 66.7%, 33.3%, and 55.6%, respectively in AGEP. 7. The mean duration of pustules was 32.9 days in GPP and 7.2 days in AGEP. 8. Reccurences of generalized pustular eruption were 46.9% in GPP and 0% in AGEP. 9. Laboratory findings revealed leukocytosis(34.4%), elevated erythrocyte sedimentation rate(28.1%), hypoalbuminamia(25.0%), and eosinophilia(6.3%) in GPP, whereas 77.8%, 55.6%, 33.3%, and 71.4%, respectively in AGEP. 10. GPP and AGEP are diseases sharing similar clinical features, but these two diseases show distinctive clinical, laboratory, and histologic features. We suggest that it is important to be aware of these distinctions for avoidance of unnecessary aggressive therapy indicated for GPP.

Two Cases of Generalized Pustular Psoriasis Followed by Acquired Bullous Disease

We herein present two cases of generalized pustular psoriasis(GPP) followed by acquired bullous diseases during antipsoriatic management. Although there were several reports de-scribing the coexistence of psoriasis vulgaris and autoimmune bullous diseases such as bullous pemphigoid or pemphigus vulgaris(PV), a coexistence of GPP and bullous disease was sparcely reported. In one patient, we could define atypical autoantigen which was distinct from the other known antigens in documented cases of bullous diseases. The other case was compatible with PV. The psoriatic lesions and bullous eruptions of the two patients cleared in several weeks after administration of cyclosporine.

A Case of Generalized Pustular Psoriasis / 대한피부과학회지

We present a case of generalized pustular psoriasis in a 47-year-old female who was treated with cyclosporine and methotrexate. She developed generalized pustular eruptions after irregular therapy of steroid and etretinate for severe psoriasis. Treatment with cyclosporine and a steroid supplement produced much improvement, but during the tapering of cyclosporine there was aggravation with pusutules and fever. She was placed on methotrexate therapy. The pustules and erythema began to remit, and eventual clearing of the skin lesions was achieved in 4 months after introduction of methotrexate.

A Case of Generalized Putular Psoriasis after Varicella Infection

Generalized pustular psoriasis is the most servere form of psoriasis. This disorder is characterized by pustular skin lesions general symptoms such as high fever, weakness and peripheral blood leukocytosis. We have experienced a case of generalized pustular psoriasis after suffering from chickenpox which was diagnosed by clinical symptoms and pathologic features from a skin biopsy. This 4-year-old male patient was managed by local and oral corticosteroid therapy with excellent outcome. A brief review of the related literature is also included.

Two Cases of Combined Geographic Tongue and Fissured Tongue in Generalized Pustular Psoriasis / 대한피부과학회지

Generalized pustular psoriasis is a rare disease, even psoriasis involving oral mucosa is very rare. There are many reports of tongue lesions in patients with psoriasis that are clinically and histologically indistinguishable from geographic tongue, and there are many reports of fissured tongue in association with psoriasis. It has been debated whether oral psoriasis exists or not, or occurs as part of generalized pustular psoriasis. We experienced two cases of combined geographic tongue and fissured tongue in patient with generalized pustular psoriasis, and report these cases with review of the literature about the oral lesions in psoriasis, geographic tongue, and fissured tongue.

Generalized pustular psoriasis, Clinical study, Psoriasis / 대한피부과학회지

BACKGROUND: Generalized pustular psoriasis(GPP) is an uncommon from of psoriasis in which a widespread eruption of sterile oustules occurs. In Korea some cases of generalized pustular psoriasis have been reported, but clinical reviews on generalized pustular psoriasis are not available. OBJECTIVE: We investegated the clinical and laboratory findings in some patients with generalized pustular psoriasis in Korea. METHODS: We studied the clinical and laboratory findings in 27 patients with generalized pustular psoriasis who visited Seoul National University hospital during the past 10 years. All the data were analyzed in total of patients with generalized pustular psoriasis, and analyzed after the patients were separated into 4 clinical types. RESULTS: 1. The male to female ratio was 1:2, and the average age of the first onset of GPP was 27.1 years. 2. The number of patients with previous history of psoriasis vulgaris were 19(70.4%). In these patients, the average age at the onset of psoriasis vulgaris was 23.4 years, and average age at the onset of GPP was 34.3 years. 3. The number of patients with a family history of psoriasis were 2(7.4%) 4. The number of patients with possible provocative factors were 16(59.3%). Systemic corticosteroid therapy was done before the onset of GPP in 7 patients, and was the most common provocative factor. 5. Fever(70.4%), chill(33.3%), and arthralgia(18.5%) were common systemic symptoms associated with GPP. 6. In laboratory tests, leukocytosis(63%), elevated ESR(62.5%), hypoalbuminemia(40.7%), and decreased cortisol(32.5%) were often found. 7. With the clinical types, the acute generalized type was 59.3%, juvenile and infantile type 25. 9%, annular and circinate type 7.4%, and GPP during pregnancy was 7.4%. In juvenile and in fantile type, patients with a previous history of psoriasis vulgaris and possible provocative factors of GPP were much less common than in the other types. CONCLUSION: In patients with GPP in Korea, a family history of psoriasis is much less frequent than in western countries. In the possible provocative factors of GPP, systemic corticosteroid therapy was the most common, so it is recommended that systemic steroid therapy should be avoided in the treatment of psoriasis vulgaris. In the comparison of the 4 clinical types, juvenile and infantile type showed a marked iifference in that GPP occurred spontaneously without any previous history of psoriasis and with no provocative factors.