Acute Generalized Pustular Psoriasis Research Articles

Spesolimab Reduces Inflammation in Generalized Pustular Psoriasis: Molecular Characterization of Flare Treatment in EFFISAYIL 1

EFFISAYIL® 1 was a randomized, placebo-controlled study of spesolimab, an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis (GPP) flare. Treatment with spesolimab led to more rapid pustular and skin clearance versus placebo in approximately half of the patients. Here we present histologic, transcriptomic, and proteomic analyses of lesional and non-lesional skin, and whole-blood samples collected from EFFISAYIL® 1. Treatment with spesolimab led to a transition toward a non-lesional profile, with a downregulation of gene expression in the skin of IL-36 transcripts (IL-36α, IL-36β, IL-36γ) and those associated with neutrophil recruitment (CXCL1, CXCL6, CXCL8), proinflammatory cytokines (IL-6, IL-19, IL-20), and skin inflammation (DEFB4A, S100A7, S100A8). Changes were manifest at Week 1 and sustained to Week 8. At the systemic level, reductions in serum biomarkers of inflammation (IL-17, IL-8, IL-6) were sustained until 12 weeks post-spesolimab treatment. Considerable overlap was observed in the spesolimab-induced changes in gene and protein expression from skin and blood samples, demonstrating the molecular basis of the effects of spesolimab on controlling local and systemic inflammation. Data are consistent with the mode of action of spesolimab, whereby inhibition of the IL-36 pathway leads to subsequent reductions in the key local and systemic pathologic events associated with acute GPP flares.

Spesolimab: A Review of the First IL-36 Blocker Approved for Generalized Pustular Psoriasis.

This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP). A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023. Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included. In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab. Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents. Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.

Expected Spesolimab Plasma Exposure following Intravenous and Subcutaneous Dosing in Patients with Generalized Pustular Psoriasis

Introduction: Generalized pustular psoriasis (GPP) is a chronic, potentially life-threatening inflammatory skin disease characterized by widespread flares of sterile pustules. Spesolimab is a first-in-class anti-interleukin-36 receptor monoclonal antibody approved to treat GPP flares in adults via intravenous (IV) infusion. The aim of this study was to simulate the plasma pharmacokinetics (PK) of IV versus subcutaneous (SC) doses of spesolimab to compare drug exposure profiles and support dosing strategies in patients with GPP.
 Methods: A population PK model was developed using individual-level PK, anti-drug antibody, and covariate data from eighteen studies in which subjects were treated with IV or SC spesolimab.1 The resulting PK model was used to simulate concentration-time profiles following varying doses of IV and SC spesolimab. Peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), and area under the curve (AUC) were summarized for each dose regimen.
 Results: Simulated spesolimab exposures demonstrated that the Cmax and AUC of the single dose 900 mg IV infusion consistently exceeded that of various single doses of SC spesolimab tested. A SC dose greater than two-fold higher would be required to attain a Cmax comparable to that of spesolimab 900 mg IV. The difference in exposure between the two administration routes was most pronounced in the first 2 weeks after administration. Slow absorption is expected with SC injection, with Tmax attained at later time points after SC dosing compared to immediately following the 90-minute infusion for IV dosing. Results were the same when simulating a two-dose regimen administered one week apart.
 Conclusions: PK simulations suggest that treatment with IV and SC spesolimab can result in differences in drug exposure in clinical practice. The immediate and high exposure of IV spesolimab compared with the lower exposure of SC spesolimab are supportive of IV dosing with spesolimab in acute GPP flare treatment vs SC dosing.

Exploring the Clinical Presentation, Course, and Burden of Disease in Generalized Pustular Psoriasis [Podcast

Generalized pustular psoriasis (GPP) is the most severe form of pustular psoriasis and affects large areas of the body. GPP is a rare disease, and has a variable presentation; thus, its diagnosis is challenging. The onset of symptoms is rapid, with the appearance of painful skin erythema, followed by the widespread eruption of sterile pustules. Acute GPP (called a flare) is often accompanied by systemic symptoms, including high fever, pain in skin lesions, malaise, and fatigue. Approximately half of GPP flares require hospitalization, with an average inpatient duration of 10-14 days. GPP prevalence estimates range from approximately 2-124 cases per million persons, with a female predominance. The most common age of onset of GPP is 40-60 years, although cases have been described in younger adults and children. GPP affects every aspect of patients' lives and has a high physical and psycho-social impact. Recent research on the interleukin-36 pathway associated with GPP led to the development of a GPP-specific treatment, spesolimab, which was approved by the US FDA in September 2022. This podcast explores the clinical presentation, disease course, and burden of disease in GPP, including differential diagnosis and common triggers of an acute flare.

Clinical profile of patients with acute generalized pustular psoriasis with and without IL36RN mutations in multi-ethnic Johor Bahru, Malaysia.

Generalized Pustular psoriasis (GPP), a rare and potentially life-threatening auto-inflammatory disease, is associated with IL36RN mutations. Here, we analyse the prevalence of IL36RN mutations in our multi-ethnic GPP cohort and assess differences in the clinical profile of patients with (IL36RN-positive) and without (IL36RN-negative) mutations. IL36RN mutations were present in 17.7% of 137 GPP patients (29.7% of Chinese cases, 17.3% of Malay cases, but 0% of Indian patients). 92% of these individuals carried the c.115 + 6T > C mutation. Male: female ratio was 1:2.3. Females predominate in both groups with no significant difference between IL36RN-positive and IL36RN-negative individuals. The overall mean age (±SD) at disease onset for GPP was 37.6 ± 17.2 years, but disease onset was significantly earlier in IL36RN-positive vs IL36RN-negative cases (mean age:30.6 ± 18.92 vs. 39.2 ± 16.49 years, p=0.027). IL36RN-positive patients were less likely to have associated plaque psoriasis (52.4% vs. 83.5%, p-value=0.002). There was no difference in the common clinical and laboratory manifestations or triggers of GPP between IL36RN-positive and -negative patients, except for geographic tongue which was significantly more common in IL36RN-positive patients (41.7% vs. 11.9%, p-value=0.002). Annual flare rate was significantly higher in IL36RN-positive compared to IL36RN-negative (mean ± SD of 1.92 ± 1.32 vs. 1.46 ± 0.90, p=0.041) cases. However, no significant difference in the rate of hospitalization and length of hospital stay was observed between the two groups. These observations demonstrate that IL36RN disease alleles occur with varying frequencies among Asian populations and are associated with a severe, early-onset clinical phenotype.

Pustular psoriasis treated with IL-17a antibody secukinumab

The article presents clinical cases of treatment of acute generalized pustular psoriasis (GPP) with the use of an interleukin IL-17A inhibitor, secukinumab, which showed a remarkable response with almost complete disappearance of pustules after the first injection. To the best of our knowledge, there are limited data in the literature on evaluating the effectiveness of therapy with genetically engineered drugs in the treatment of GPP.

Sociodemographic, clinical, laboratory, treatment and prognostic characteristics of 156 generalized pustular psoriasis patients in Turkey: a multicentre case series.

Generalized pustular psoriasis (GPP) is a rare and severe inflammatory disease characterized by widespread and superficial sterile pustules on an erythematous background. This multicentre study aimed to determine the clinical profile and course in a large cohort of patients with GPP. One hundred and fifty-six GPP patients (mean age, 44.2 ± 18.7 years) who met the diagnostic criteria of the European Consensus Report of GPP were included in the study. Sociodemographic characteristics, quality of life, triggering factors of the disease, clinical, laboratory, treatment and prognostic features were evaluated. 61.5% of the patients were female. The rate of working at or below the minimum wage (≤$332.5/month) was 44.9%. Drugs (36.5%) were the most common trigger. While hypocalcaemia (35.7%) was the most important cause of GPP during pregnancy, systemic steroid withdrawal (20%) was the most frequently reported trigger for infantile/juvenile and mixed-type GPP (15%) (P < 0.05). Acute GPP (53.8%) was the most common clinic. Nails were affected in 43.6% of patients, and subungual yellow spots (28.2%) were the most common change. In annular GPP, fever (P < 0.001) and relapse frequency (P = 0.006) were lower than other subtypes, and the number of hospitalizations (P = 0.002) was lower than acute GPP. GPP appeared at a later age in those with a history of psoriasis (P = 0.045). DLQI score (P = 0.049) and joint involvement (P = 0.016) were also higher in this group. Infantile/juvenile GPP was observed in 16.02% of all patients, and arthritis was lower in this group (24.4 vs. 16%). GPP of pregnancy had the worst prognosis due to abortion observed in three patients. Recent advances in treatment have improved mortality associated with GPP, but abortion remains a significant complication. Although TNF-α inhibitors have proven efficacy in GPP, they can also trigger the disease. Mixed-type GPP is more similar to acute GPP than annular GPP with systemic manifestations and course.

Clinical Course and Characteristics of Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by episodes of widespread sterile macroscopic pustules, with or without systemic inflammation and/or plaque psoriasis. Multiple GPP subtypes have been described, from acute GPP of von Zumbusch to milder, annular pustular psoriasis. Generalized pustular psoriasis mainly affects adults, with a female preponderance, but juvenile GPP also occurs. Flares are a hallmark of GPP and may occur de novo or be provoked by triggers, including withdrawal of systemic corticosteroids, infections, stress, pregnancy, and menstruation. Severity of flares varies widely between patients, and between flares in an individual patient. Significant flares are often accompanied by systemic symptoms, notably fever, general malaise, and extracutaneous manifestations such as arthritis, uveitis, and neutrophilic cholangitis. Common laboratory abnormalities include neutrophilia, elevated C-reactive protein levels, hypocalcemia, and abnormal liver function tests. The clinical course of GPP is highly variable; it can be a relapsing disease with recurrent flares and no pustulation between flares or a persistent disease with perpetual mild pustulation punctuated with flares of greater severity. Patients may have multiple flares per year or a flare every few years. Most flares last 2–5 weeks and approximately 50% require hospitalization. Life-threatening complications include sepsis and renal, hepatic, respiratory, and heart failure. Reported mortality rates are 2–16%.

26590 Design and rationale of Effisayil 1, a Phase II, multicenter, randomized, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis with an acute flare

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by recurrent flares of widespread skin eruptions of neutrophilic aseptic pustules that occur with or without systemic inflammation. Therapeutic intervention is a major challenge; globally, there are no approved treatments for acute GPP flares and there is a lack of robust clinical evidence to guide GPP treatment. Rapid improvements in skin symptoms with a single intravenous dose of spesolimab, an anti-IL-36 receptor antibody, was shown in a prior Phase I study.

26591 Characterization of flares in patients with generalized pustular psoriasis—A population-based study from the French National Health Data System database (SNDS)

Generalized pustular psoriasis (GPP) is a rare, neutrophilic skin disease characterized by recurrent episodes of widespread eruption of sterile pustules occurring with or without systemic inflammation and/or plaque psoriasis. Acute GPP flares can be severe and even life-threatening, and patient identification using administrative claims databases is difficult. This study aimed to develop an algorithm to identify and describe the characteristics of GPP flares using the French SNDS database (comprising data from 98.8% of the French population).

Diagnosis and screening of patients with generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular eruptions on inflamed, erythematous skin. It is important to recognize acute GPP as a subtype of psoriasis associated with high morbidity and mortality so therapy can be initiated without delay. Since GPP was first described in 1910 by Leopold von Zumbusch, it has been inconsistently defined, stratified, and diagnosed in the literature. Multiple definitions and diagnostic criteria have been proposed over the years. Recently, formal consensus guidelines on GPP have been published by international groups. This article reviews the current evidence and understanding in the diagnosis and screening of GPP.

Clinical features and course of generalized pustular psoriasis in Korea.

The clinical course of generalized pustular psoriasis (GPP) is variable and unpredictable. Sufficient data on the clinical course of the disease has not been reported due to its rarity. To investigate the clinical features and course of GPP according to its subtypes, medical records of patients diagnosed with GPP from 2002 to 2012 at two tertiary hospitals were reviewed. The data included patient demographics, associated symptoms, aggravating factors, patterns of relapse and prognosis. Thirty-three patients with GPP were included in our study, with a mean age of 45.6years and a male:female ratio of 1:1.2. Patients were categorized based on the following subtypes: acute GPP, 21 (63.6%); GPP of pregnancy, two (6.1%); juvenile GPP, three (9.1%); and annular GPP, seven (21.2%). In the acute GPP population, skin lesions cleared within 2months in 11 (73.3%) patients, and six (40.0%) of these had no relapse. Severe complications, abortion or death, were observed in two patients (100.0%) with GPP of pregnancy. Nineteen (76.0%) of the GPP patients experienced persistence or relapse of skin lesions. The patterns of skin lesions upon relapse included plaques in six patients (31.6%), pustules in eight patients (42.1%), and plaques and pustules in five patients (26.3%). Among acute GPP patients, 16.7% of patients with no relapse had a history of plaque psoriasis. However, 77.8% of patients with persistence and relapse in their clinical course had a history of plaque psoriasis. In conclusion, our study presents the detailed clinical course of GPP by subtype in Korean patients.

Two cases of generalized pustular psoriasis: successful treatment with infliximab.

Dear Editor: In case 1, a 41-year-old woman presented with a 3-year history of recurrent pustules on erythematous skin. The patient had been treated with methotrexate, sulfasalazine and cyclosporine for psoriatic arthritis and generalized pustular psoriasis (GPP) for 2 years. However, these treatments failed to yield satisfactory improvement. Physical examination revealed the presence of extensive erythematous patches with pustules over the entire body (Fig. 1A) and inflammatory arthritis was noted in the distal interphalangeal, sacroiliac and knee joints. We decided to use infliximab (3 mg/kg) to treat the GPP and psoriatic arthritis. The patient's pustular lesions cleared quickly within 48 hours after the first injection. After the second injection of infliximab (3 mg/kg), marked improvement in arthralgia was observed (Fig. 1B). She has since been receiving infliximab 3 mg/kg every 8 weeks as maintenance therapy. No recurrence of pustules or arthritis symptoms has been detected during 12 months of follow-up. Fig. 1 Pustular psoriasis in case 1 (A). Marked improvement was observed after the second injection of infliximab (B). In case 2, a 39-year-old woman with a 20-year history of plaque type psoriasis was admitted to our department for lower limb cellulitis. Rapid resolution of cellulitis was achieved after systemic antibiotic treatment (cefazolin 6 g/day). Three days after antibiotic treatment, she experienced abrupt onset of pustules on erythematous skin affecting more than 90% of body (Fig. 2A, B). She was initially treated with infliximab (3 mg/kg) combined with acitretin (30 mg/day) for pustular flares. Within 48 hours of the first infusion, the pustules were resolved, but diffuse erythema on the trunk and extremities remained (Fig. 2C, D). The patient received acitretin (20 mg/day) for maintenance after a single dose of infliximab. No relapse of the pustules has been noted, but mild psoriatic plaques have followed. Fig. 2 Generalized pustular papules on the entire body in case 2 (A, B). Near remission of a pustular eruption was seen 48 hours after infliximab infusion (C, D). Infliximab is a chimeric immunoglobulin G1 anti-tumor necrosis factor-α monoclonal antibody that is effective in treating moderate to severe psoriasis and psoriatic arthritis1. Several studies have documented a rapid improvement in recalcitrant GPP with infliximab (5 mg/kg)2,3. Because infliximab has a faster onset of action than that of other modalities including biologics, some researchers recommended that infliximab be used as the first-line treatment modality in patients with severe and acute GPP4. Both patients in the current study experienced dramatic resolution of pustules within 48~72 hours of infliximab infusion without any serious adverse events. Although the optimal infliximab dose and maintenance regimen for GPP has not yet been established, low dose (3 mg/kg) of infliximab showed excellent response in the current cases. In an earlier report, there was no significant difference between the 3 mg/kg treatment group and the 5 mg/kg treatment group for moderate to severe psoriasis5. However, more research is needed and we believed that low dose infliximab with or without acitretin may have an effect on acute GPP. Since infliximab appears to offer the advantage of rapid response and reduced morbidity, we may consider it extremely effective and well tolerated in adult patients with severe and acute GPP. However, since GPP tends to relapse frequently, large population studies are needed to evaluate the efficacy of maintenance infliximab therapy for GPP with recurrent pustular episodes.

Clinical profile, morbidity, and outcome of adult‐onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia

Generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis. Our objective is to review the clinical profile, comorbidities, and outcome of patients with GPP. A retrospective note review of all patients with adult-onset GPP. A total of 102 patients with adult-onset GPP were diagnosed between 1989 and November 2011, with a female to male ratio of 2:1. The mean age at onset of GPP was 40.9years (range: 21-81years). Acute GPP was the most common variant seen (95 cases), followed by four localized variants of GPP and three with annular pustular psoriasis. Fever and painful skin were present in 89% of patients, arthritis in 34.7%, and leukocytosis in 78.4%. Common triggers were systemic steroids (45 cases), pregnancy (17 cases), and upper respiratory tract infections (16 cases). A positive family history of psoriasis and GPP was present in 29% and 11%, respectively. Comorbidities included obesity (42.9%), hypertension (25.7%), hyperlipidemia (25.7%), and diabetes mellitus (23.7%). The mean duration of admission and pustular flare for acute GPP was 10.3days (range: 3-44days) and 16days (range: 7-60days), respectively. Fifty-four patients responded to systemic retinoid, 21 to methotrexate, eight to cyclosporine, and one to adalimumab, but recurrences were common. Our study confirms the poor response of GPP to currently available anti-psoriatic agents, with frequent flare-ups. There is a need for a more effective targeted therapy for this condition.

Clinical and Laboratory Features in Acute Generalized Pustular Psoriasis

Acute generalized pustular psoriasis (AGPP) is a rare variant of psoriasis that can be lethal without proper treatment. It can be caused by the withdrawal of corticosteroids and, among its extra-cutaneous manifestations, liver abnormalities are frequently under-reported or attributed to drugs. The aim of this study was to assess the clinical and laboratory data, treatment options, and disease outcome in patients with AGPP and to search for significant differences between subgroups of these patients. This was a retrospective analysis of the clinical files from inpatients with AGPP observed in our department between 1973 and 2008. Statistical tests were performed at a significance level of 5%. This was an inpatient, single-center study. Outcome measures were a previous history of psoriasis, corticosteroid use before admittance, mortality rate, white blood cell count, absolute neutrophil count, and abnormalities in liver enzymes. A total of 34 patients fulfilled the inclusion criteria, of whom 61% were men and 65% had a previous history of psoriasis vulgaris. Topical corticosteroids were applied by 50% of patients before admittance. Skin lesions remitted with methotrexate, etretinate, or acitretin treatment in all but two patients who died of sepsis. Abnormalities in liver enzymes were present in 47% of patients. Patients without a previous history of psoriasis had a significantly younger age at the first episode of AGPP. In the comparison between the groups of patients with and without liver abnormalities, a male preponderance and higher leukocyte counts were found in the former, with a positive correlation between the absolute neutrophil count and total bilirubin also being observed. Previous use of retinoids or methotrexate was not associated with these hepatic alterations. Limitations of the data were that this was a single-center, retrospective study with a small sample size. Withdrawal of systemic or topical corticosteroids can precipitate or worsen AGPP and these agents should not be used in these patients. Liver abnormalities can be considered an extra-cutaneous manifestation of AGPP. As in other series, no association between the use of drugs and changes in liver tests was found and therefore the deleterious withdrawal of efficient drugs, namely acitretin and methotrexate, should be avoided.

Production of Interleukin 8 by Circulating CLA + T Cells With Skin Tropism in Patients With Psoriasis and in Healthy Controls

Background Psoriasis is an immune-mediated disease typically associated with cutaneous neutrophilic infiltration and Munro microabscesses. Interleukin (IL)-8 is one of the main neutrophil-attracting chemokines. Although keratinocytes have traditionally been considered to be the principal source of IL-8 in psoriasis, we present data that suggest that cutaneous lymphocyte associated antigen CLA + T lymphocytes synthesize this cytokine. Material and methods Six patients with psoriasis and 6 healthy controls were studied. Immunomagnetic separation was used to isolate CLA + and CLA − T lymphocytes and IL-8 and interferon (IFN)-γ production was quantified for each cell subpopulation using enzyme-linked immunosorbent assay. Finally, gene expression of IL-8 was analyzed by reverse transcriptase-polymerase chain reaction. Results CLA + and CLA − T lymphocytes from patients with psoriasis and from controls showed a significantly increased production of IFN-γ when activated, whereas only activated CLA + T lymphocytes (from patients and controls) synthesized IL-8. The higher level of expression of IL-8 and IFN-γ by CLA + T lymphocytes in comparison to CLA − cells was confirmed. Discussion Previous studies have confirmed IL-8 production by T lymphocytes in inflammatory skin diseases with neutrophil-rich infiltrates, such as acute generalized exanthematous pustulosis, Behçet disease, and pustular psoriasis. We have confirmed the role of the subset of T lymphocytes with skin tropism (CLA +) in IL-8 production in nonpustular psoriasis.

Producción preferente de IL-8 por linfocitos T CLA+ circulantes con tropismo cutáneo en pacientes con psoriasis y en sujetos sanos

Background Psoriasis is an immune-mediated disease typically associated with cutaneous neutrophilic infiltration and Munro microabscesses. Interleukin (IL)-8 is one of the main neutrophil-attracting chemokines. Although keratinocytes have traditionally been considered to be the principal source of IL-8 in psoriasis, we present data that suggest that cutaneous lymphocyte associated antigen (CLA)+ T lymphocytes synthesize this cytokine. Material and methods Six patients with psoriasis and 6 healthy controls were studied. Immunomagnetic separation was used to isolate CLA+ and CLA– T lymphocytes and IL-8 and interferon (IFN)-γ production was quantified for each cell subpopulation using enzyme–linked immunosorbent assay. Finally, gene expression of IL-8 was analyzed by reverse transcriptase-polymerase chain reaction. Results CLA+ and CLA− T lymphocytes from patients with psoriasis and from controls showed a significantly increased production of IFN-γ when activated, whereas only activated CLA+ T lymphocytes (from patients and controls) synthesized IL-8. The higher level of expression of IL-8 and IFN-γ by CLA+ T lymphocytes in comparison to CLA– cells was confirmed. Discussion Previous studies have confirmed IL-8 production by T lymphocytes in inflammatory skin diseases with neutrophil-rich infiltrates, such as acute generalized exanthematous pustulosis, Behçet disease, and pustular psoriasis. We have confirmed the role of the subset of T lymphocytes with skin tropism (CLA+) in IL-8 production in nonpustular psoriasis.

A dramatic response to a single dose of infliximab as rescue therapy in acute generalized pustular psoriasis of von Zumbusch associated with a neutrophilic cholangitis

Generalized pustular psoriasis of von Zumbusch is an unstable, inflammatory form of psoriasis, with the hallmark of neutrophil infiltration in cutaneous as well as extracutaneous lesions. It is often recalcitrant, making treatment difficult. Tumour necrosis factor-alpha antagonists including infliximab have been used with success in treating recalcitrant cases. We report a case of a 48-year-old Chinese female patient with a long-standing history of poorly controlled generalized pustular psoriasis which was resistant to multiple therapies. During a severe flare, a single dose of infliximab resulted in rapid clearing of cutaneous lesions, together with resolution of liver function abnormalities that are likely secondary to neutrophilic cholangitis. Subsequent maintenance therapy with acitretin allowed remission of pustular disease for 7 months. This demonstrates the efficacy of single-dose infliximab for both cutaneous lesions and systemic hepatic involvement in generalized pustular psoriasis.

A Case Report of Generalized Pustulosis With Systemic Manifestations Requiring Burn Intensive Care Unit Admission

Not infrequently patients are transferred to a burn center with the diagnosis of toxic epidermal necrolysis (TEN). Not all cases of generalized erythema and skin sloughing represent TEN. Acute generalized pustular psoriasis (AGPP) of the von Zumbusch type and acute generalized exanthematic pustulosis (AGEP) are two rare skin diseases that can also present with widespread erythema and skin sloughing. We present the case of a 55 year old morbidly obese woman with a history of severe psoriatic arthritis treated in our burn unit for generalized pustulosis, erythema, and skin sloughing. This was accompanied by respiratory failure, hypotension, acute renal failure, and elevated direct bilirubin. Skin biopsy narrowed the differential diagnosis to AGPP and AGEP. Her skin sloughing was treated as second degree burns with petrolatum gauze and mupirocin ointment. She required intubation, aggressive fluid resuscitation and inotropic support. She recovered with these measures over the course of 1 week. Like TEN, AGPP, and AGEP can involve the skin to an extent requiring burn intensive care admission. Patients can present on rare occasions with multi-system failure. We would like to raise the awareness of burn specialists regarding these rare diseases. They should be distinguished from TEN, as they tend to have better prognosis than TEN and their management can be different.

Bilateral periocular psoriasis: an initial manifestation of acute generalized pustular psoriasis with coexistent Sjögren's syndrome

A 21-year-old febrile lady presented to the emergency service with severe lid oedema, conjunctivitis, dry mouth and abdominal skin rash. Over 5 days, she developed silvery scales and pustules on the lids, and generalized pustules on an erythematous base. Multiple focal sterile corneal infiltrates were seen. Haematological investigations and a skin biopsy were done as the consulting dermatologist suspected acute generalized pustular psoriasis. In addition, secondary Sjögren's syndrome was diagnosed since she had keratoconjunctivitis sicca, xerostomia, raised erythrocyte sedimentation rate and positive antinuclear antibodies. The presence of microabscesses in the epidermis on skin biopsy confirmed the diagnosis of pustular psoriasis. With oral methotrexate 7.5 mg weekly and topical corticosteroids, the acute condition gradually resolved; however, the keratoconjunctivitis sicca is persisting. Secondary Sjögren's syndrome associated with acute generalized pustular psoriasis and ocular psoriasis is extremely rare. Awareness of the ocular and dermatological features of these two conditions would result in earlier diagnosis and institution of appropriate treatment.