Get 20M+ Full-Text Papers For Less Than $1.50/day. Subscribe now for You or Your Team.

Learn More →

Diagnosis and screening of patients with generalized pustular psoriasis

Diagnosis and screening of patients with generalized pustular psoriasis Psoriasis: Targets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article REV I EW Diagnosis and screening of patients with generalized pustular psoriasis This article was published in the following Dove Press journal: Psoriasis: Targets and Therapy Abstract: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening Karen Ly* variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular Kristen M Beck* eruptions on inflamed, erythematous skin. It is important to recognize acute GPP as a subtype Mary P Smith of psoriasis associated with high morbidity and mortality so therapy can be initiated without Quinn Thibodeaux delay. Since GPP was first described in 1910 by Leopold von Zumbusch, it has been Tina Bhutani inconsistently defined, stratified, and diagnosed in the literature. Multiple definitions and Department of Dermatology, University diagnostic criteria have been proposed over the years. Recently, formal consensus guidelines of California, San Francisco, CA, USA on GPP have been published by international groups. This article reviews the current *These authors contributed equally to evidence and understanding in the diagnosis and screening of GPP. this work Keywords: generalized pustular psoriasis, acute generalized pustular psoriasis of von Zumbusch, pustular psoriasis, diagnostic criteria Introduction Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life- threatening variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular eruptions on inflamed, erythematous skin. Prompt diagnosis of GPP may prevent morbidity from complications including sepsis, acute renal failure, high-output congestive heart failure, and acute respiratory distress syndrome. This article reviews the current evidence and understanding in the diagnosis and screening of GPP. Background In contrast to chronic plaque psoriasis, which accounts for the majority of psoriasis vulgaris (PV) cases worldwide, GPP is considered to be a rare disease. A 2018 Japanese epidemiological analysis reported that GPP represented just 1.8% of all clinical types of psoriasis. However, the exact prevalence of GPP is unknown. One reason for this is that since its first description in 1910 by Leopold von Zumbusch, it has been inconsistently defined, stratified, and diagnosed in the literature. Rigorous studies characterizing GPP have been limited by both the rarity of the disease and by multiple definitions and diagnostic criteria that have been proposed over the years. Historically, pustular psoriasis has been classified as either generalized or Correspondence: Kristen M Beck Department of Dermatology, University localized. The generalized forms are then further stratified by the acuity of pre- of California, 515 Spruce Street, San sentation, acute GPP (also known as GPP, generalized pustular psoriasis of von Francisco, CA 94118, USA Tel +1 415 476 4701 Zumbusch, or von Zumbusch type GPP) and subacute GPP (also known as annular Fax +1 415 502 4126 5–7 Email Kristen.beck@ucsf.edu pustular psoriasis (APP) or annular pattern GPP). submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 37–42 37 DovePress © 2019 Ly et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://doi.org/10.2147/PTT.S181808 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Ly et al Dovepress Acute onset GPP is the most common type, which GPP is also reported to occur at a higher incidence in 3,8 16,18 accounts for more than two-thirds of GPP cases. When women. acute GPP occurs in pregnancy, it is often termed impetigo Although many cases appear to be idiopathic, medica- herpetiformis (IH). Juvenile pustular psoriasis (JPP) is tions, infections, and pregnancy have been reported as 9,10 3,8,12 a subtype of GPP that occurs in the pediatric population. triggers of GPP. A detailed drug history is important Although some studies have included APP as a variant as it can associate the initiation or withdrawal of a drug 3,7 of GPP, this is controversial due to its subacute course and with the onset of disease. Rapid tapering of systemic mild systemic symptoms. Subacute GPP is characterized corticosteroids is a well-known and frequently reported 19,20 by annular lesions with pustules, erythema, and scaling at trigger for GPP flares. Many other medications have 3,11,12 the advancing edge. Patients typically lack systemic also been implicated as a trigger, including antibiotics such 21 22 23 symptoms and laboratory abnormalities. as amoxicillin, terbinafine, calcipotriol ointment, GPP is also distinguished from the transient, primary betamethasone ointment, tumor necrosis factor-alpha 24,25 24,26 pustule formation that may occur at the periphery of psor- (TNF-α) inhibitors, ustekinumab, and withdrawal iasis plaques in PV. This may occur in patients with PV of cyclosporine. during periods of disease exacerbation or following the Infections reported as potential etiological factors in 28 29 application of irritants, such as tars. Although this phenom- GPP include streptococcal, Trichophyton rubrum, 30,31 32 enon has been termed “localized GPP” and “psoriasis cum cytomegalovirus, Epstein-Barr virus, and vari- 2 33 pustulatione” (psoriasis with pustules), it is generally recog- cella-zoster virus. GPP has also been associated with nized that it is not a type of pustular psoriasis. various medical conditions including Turner syndrome, 34 34 hypoparathyroidism, hypocalcemia, allogeneic stem 35 36 Clinical diagnosis cell transplantation, rheumatoid arthritis, and The diagnosis of GPP should be suspected in patients with cardiomyopathy. acute onset erythema and pustulosis, and subsequently On initial evaluation, it is important to determine evaluated using clinicopathologic correlation between which patients require immediate hospitalization due to physical examination findings, patient history, review of risk of complication. Systemic symptoms including fever, symptoms, and histopathology. chills, shortness of breath, and altered mental status may GPP presents as the rapid onset of widespread, erythema- indicate the need for inpatient admission. Obtaining tous, inflamed skin studded with 2- to 3-mm sterile pustules. a history of comorbid medical conditions may also help Pustules may expand and coalesce into irregular “lakes of triage patients who are at higher risk for complications. pus.” During episodes of pustulation, patients may develop These include advanced age, congestive heart failure, renal abnormal clinical findings associated with systemic inflamma- insufficiency, diabetes mellitus, or immunodeficiency. Patients with GPP may develop life-threatening com- tion. Patients appear systemically ill, with high-grade fever, 8,11,12 plications, including sepsis, acute renal failure, neutrophi- chills, malaise, and anorexia. Erythroderma may occur. lic cholangitis, high-output congestive heart failure, acute After 1–2 days, the pustules typically resolve with residual 3 3,8 respiratory distress syndrome, and death. Mortality in erythema and desquamation. GPP is most commonly due to complications from sepsis, A physical examination of the skin and oral mucosa is 3,17 acute respiratory distress syndrome, and cardiac failure. important to evaluate the extent of skin involvement. Associated cutaneous symptoms may include pain, burn- It is therefore critical to identify which patients require ing, and pruritus. Associated mucosal findings include hospitalization for stabilization, rapid treatment, and to a geographic or fissured tongue, cheilitis, and ocular invol- reduce morbidity and mortality. 3,13 vement (eg, conjunctivitis, uveitis, iritis). Additional There is no cure for GPP. GPP may be relapsing, with extracutaneous findings may include nail abnormalities, recurrence either idiopathic or only when exposed to a trigger, 15,16 arthralgias, jaundice, and lower extremity edema. or persistent, with symptoms lasting for months. Symptoms A history of concurrent or previous PV may be helpful in may self-resolve or require aggressive treatment. confirming the diagnosis; however, not all patients have a history of psoriasis. GPP may occur with or without Laboratory abnormalities 3,17,18 ahistoryof PV. GPP may affect patients at any age, Laboratory evaluations are strongly recommended and 3,13,16 but most commonly affects patients in the fourth decade. deemed necessary to assess for severity and potential submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 DovePress Dovepress Ly et al due to medications. complications associated with GPP. Laboratory abnormalities It presents as sterile pustules on an would be consistent with the systemic involvement seen in erythematous base and can be clinically and histologically GPP, the most common of which are leukocytosis with neu- difficult to differentiate from GPP. Clinically, AGEP has trophilia and elevated erythrocyte sedimentation rate (ESR). a more abrupt onset, shorter duration, does not recur, has Complete blood count with differential (to evaluate for leuko- no personal or family history of PV, and is associated with 38,41 cytosis and lymphopenia) and a comprehensive metabolic a recently initiated medication. AGEP may also be panel (to evaluate for hypocalcemia, other electrolyte abnorm- accompanied by blood eosinophilia. alities, hypoalbuminemia, and to evaluate liver and renal func- tion) are common initial assessments. Skin desquamation and Genetic screening epidermal barrier disruption may result in electrolyte abnorm- Although the etiology of GPP remains to be fully eluci- alities. Hypocalcemia can occur as a result of hypoalbumine- dated, a genetic basis that may cause or contribute to mia, but ionized calcium is typically normal and patients are pustular variants of psoriasis, distinct from that of chronic 8,12 asymptomatic. Patients may have increased alkaline phos- plaque psoriasis, has been identified. 6,8 phatase, transaminase, and bilirubin levels. Patient who In recent years, genetic studies have identified three report an antecedent upper respiratory infection may have gene mutations in one or more forms of pustular psoriasis- positive anti-streptolysin titers. mutations in IL36RN (encodes IL-36 receptor antagonist), Cultures of pustules and blood samples, gram stains, CARD14 (encodes a keratinocyte adaptor protein), and and potassium hydroxide preparation can also be per- AP1S3 (encodes a subunit of the adaptor protein 1 com- formed to rule out other causes of pustulosis. plex). These three mutations account for fewer than 30% of GPP cases. IL36RN mutations are the most frequent genetic abnormality observed in pustular psoriasis and Histopathology 38 occur in approximately 20% of GPP patients. AP1S3 Skin biopsy is important to confirm the diagnosis of GPP. and CARD14 variants are found in fewer than 10% of The histopathology of GPP is characterized by Kogoj’s spon- these patients. giform pustules, which are the accumulations of neutrophils Currently, genetic screenings for IL36RN, CARD14, under the stratum corneum, as well as the classic findings of and AP1S3 mutations are not routinely indicated. psoriasis, which include parakeratosis, acanthosis, hyperkera- However, IL36RN mutations are being increasingly used tosis, elongation of rete ridges, diminished stratum granulo- to aid in the diagnosis of GPP. Genotype–phenotype stu- sum, capillary dilation of the papillary dermis, Munro’s dies have shown that IL36RN mutations are associated microabscesses, and superficial perivascular mononuclear with an earlier age of onset in GPP, widespread inflamma- cell infiltrations. The edema and inflammatory cell infiltrate 18,43,44 11,37–39 tion, and are not associated with concurrent PV. is notably greater than what is observed in PV. When this clinical triad is present in familial IL36RN Other diseases with similar histopathology include mutations, it is described by the acronym DITRA (defi- acute generalized exanthematous pustulosis (AGEP). ciency of the interleukin 36 receptor antagonist). However, the additional presence of eosinophils and Twelves et al demonstrated that IL36RN mutations were necrotic keratinocytes, which are suggestive of an under- 40 associated with an earlier age of onset across all pustular lying drug trigger, would likely be seen. psoriasis subtypes, with the youngest age of onset found in GPP patients (mean age of onset 31 years ±19.7 years). Differential diagnosis Based on this finding, this study recommended that The list of differential diagnoses for GPP is vast and patients who present with GPP before age 30 be screened includes many cutaneous pustular diseases, including for IL36RN mutations. AGEP, subacute annular pustular psoriasis (APP), loca- lized forms of pustular psoriasis (eg, palmoplantar pustular Proposed diagnostic criteria psoriasis, Acrodermatitis continua of Hallopeau), pemphi- Recent consensus guidelines on GPP have been published gus foliaceus, IgA pemphigus, and subcorneal pustular by European and Japanese groups in order to distinguish 11,38 dermatosis. GPP from other pustular diseases (Table 1). One goal of The most important diagnosis to exclude is AGEP, these guidelines is to develop an extended cohort using a rare and severe pustular skin reaction, most commonly standard classification in order to reveal clinical and genetic submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 39 DovePress Ly et al Dovepress Table 1 Summary of diagnostic criteria persisted for more than three months. No severity assess- ment was published with this report. However, ERASPEN Year Diagnostic Criteria did acknowledge the need for updated severity criteria. It Umezawa et al 2003 1. Systemic symptoms such as fever was thought that using the number of pustules present to and malaise measure severity would be limited by the diverse morphol- 2. Multiple, isolated septic pustules on ogy of GPP, which may include either discrete or confluent erythematous skin 3. Kogoj’s spongiform pustules are his- pustules. If a patient presents with mixed types of pustular topathologically confirmed psoriasis (eg, both GPP and a localized form of pustular 4. Laboratory abnormalities, including psoriasis, such as Arodermatitis continua of Hallopeau), left shift leukocytosis, elevated ESR, then the patient should be classified according to the most elevated C-reactive protein (CRP), predominant feature. elevated anti-streptolysin O antibody The Japanese guideline was published in 2018 by the levels, elevated IgG or IgA, hypopro- teinemia, hypocalcemia Japanese Dermatological Association and the Study Group 5. Recurrence of these clinical and for Rare Intractable Skin Diseases as an update to histological findings 37 Umezawa et al’s 2003 GPP guideline. This guideline Navarini et al 2017 Primary, sterile, macroscopically visible by Fujita et al defines GPP as a rare disease in which epidermal pustules on non-acral skin acute fever, generalized skin rashes, and many sterile Subclassifiers pustules develop. Histopathologically, GPP forms subcor- 1. With or without systemic inflam- mation neal pustules characterized by Kogoj’s spongiform pus- 2. With or without plaque psoriasis tules. GPP may or may not be preceded by PV and is 3. Either relapsing (>1 episode) or characterized by repeated disease recurrence. During the persistent (>3 months) course of the disease, patients have abnormal clinical Fujita et al 2018 1. Systemic symptoms such as fever findings associated with systemic inflammation and often and fatigue present with mucosal symptoms and arthritis as complica- 2. Systemic or extensive flush accom- panied by multiple sterile pustules tions. Although rare, GPP may be accompanied by certain 3. Neutrophilic subcorneal pustules eye symptoms and secondary amyloidosis. histopathologically characterized by Fujita et al made a few important additions to the defini- Kogoj’s spongiform pustules tion of GPP. The definition was updated to include that GPP 4. Recurrence of these clinical and may have potential complications of arthritis, mucosal and histological findings ocular symptoms, and secondary amyloidosis. This addition Adefinitive diagnosis of GPP can be made in patients with all 4 features. to the definition was made to emphasize that GPP involves GPP would be suspected in those with more than just skin lesions, it causes systemic inflammation features 2 and 3. and has the potential for serious complications. Another Abbreviations: ESR, erythrocyte sedimentation rate; GPP, generalized pustular significant difference between the 2003 and 2018 Japanese psoriasis. criteria was the removal of laboratory abnormalities from the criteria. This was due to insufficient sensitivity and specifi- insights into patient demographics, clinical features, and city of laboratory abnormalities in the diagnosis of GPP; genetic mutations that may improve diagnosis and early instead, laboratory abnormalities were strongly recom- treatment of this potentially life-threatening disease. mended and deemed necessary to assess for severity and In 2017, the European Rare and Severe Psoriasis potential complications (Table 2). Expert Network (ERASPEN) published the first European consensus statement on the phenotypes of pust- Conclusion ular psoriasis. GPP was defined as primary, sterile, macro- The diagnosis of GPP can be challenging due to its rarity, scopically visible pustules on non-acral skin. In addition to heterogeneous presentation, and lack of consistent classi- this, the criteria included subclassifiers that indicate if GPP fication, but it is important to recognize acute GPP as occurs with or without PV and with or without systemic a potentially fatal subtype of psoriasis so therapy can be inflammation. The criteria also specify that a diagnosis of initiated without delay. GPP is diagnosed based on the GPP can only be made when the condition has relapsed or presence of visible pustules on erythematous skin with submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 DovePress Dovepress Ly et al Table 2 Summary of assessments included in criteria Systemic symptoms Pustules Histology Laboratory abnormalities Recurrence PV Umezawa et al ++ + + + − Navarini et al ±+ −− +± Fujita et al ++ + − + − Notes: + indicates present; ± indicates present or absent; - indicates absent. Abbreviation: PV, psoriasis vulgaris. 8. Borges-Costa J, Silva R, Goncalves L, Filipe P, Soares de Almeida L, confirmation from histopathology, and supportive evidence Marques Gomes M. Clinical and laboratory features in acute generalized from laboratory and genetic evaluations. The most impor- pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol. tant diagnosis to exclude is AGEP. 2011;12(4):271–276. doi:10.2165/11586900-000000000-00000 9. de Oliveira ST, Maragno L, Arnone M, Fonseca Takahashi MD, Romiti R. These findings are reflected in recent consensus guide- Generalized pustular psoriasis in childhood. Pediatr Dermatol. 2010;27 lines by the ERASPEN and the Japanese Dermatological (4):349–354. doi:10.1111/j.1525-1470.2010.01084.x 2,14 10. Lau BW, Lim DZ, Capon F, Barker JN, Choon SE. Juvenile general- Association. Both guidelines share two features: the ized pustular psoriasis is a chronic recalcitrant disease: an analysis of clinical presence of pustules and disease recurrence. 27 patients seen in a tertiary hospital in Johor, Malaysia. Other requirements for diagnosis such as systemic inflam- Int J Dermatol. 2017;56(4):392–399. doi:10.1111/ijd.13489 11. Naik HB, Cowen EW. Autoinflammatory pustular neutrophilic mation, Kogoj’s spongiform pustules, and laboratory diseases. Dermatol Clin. 2013;31(3):405–425. doi:10.1016/j. 14,37,46 abnormalities vary depending on the criteria used. det.2013.04.001 12. Baker H, Ryan TJ. Generalized pustular psoriasis. A clinical and These diagnostic criteria can be utilized for the assessment epidemiological study of 104 cases. Br J Dermatol. 1968;80 and diagnosis of GPP, but there remains a need for (12):771–793. a unified diagnostic criteria that can be universally adopted 13. Jin H, Cho HH, Kim WJ, et al. Clinical features and course of generalized pustular psoriasis in Korea. J Dermatol. 2015;42 and allow for further characterization of GPP in larger (7):674–678. doi:10.1111/1346-8138.12863 cohorts. Further genetic studies are needed to determine 14. Fujita H, Terui T, Hayama K, et al. Japanese guidelines for the management and treatment of generalized pustular psoriasis: the the clinical significance of known genetic mutations in the new pathogenesis and treatment of GPP. J Dermatol. 2018;45 classification, diagnosis, and screening of GPP. (11):1235–1270. doi:10.1111/1346-8138.14523 15. Viguier M, Allez M, Zagdanski AM, et al. High frequency of cho- lestasis in generalized pustular psoriasis: evidence for neutrophilic Disclosure involvement of the biliary tract. Hepatology. 2004;40(2):452–458. doi:10.1002/hep.20305 The authors report no conflicts of interest in this work. 16. Tay YK, Tham SN. The profile and outcome of pustular psoriasis in Singapore: a report of 28 cases. Int J Dermatol. 1997;36(4):266–271. 17. Hoegler KM, John AM, Handler MZ, Schwartz RA. Generalized References pustular psoriasis: a review and update on treatment. J Eur Acad Dermatol Venereol. 2018;32(10):1645–1651. doi:10.1111/jdv.14949 1. Zumbusch V. Leopold. Psoriasis and pustuloses Exanthem. Arch 18. Twelves S, Mostafa A, Dand N, et al. Clinical and genetic differences Dermatol Syphilol. 1910;99:335–346. doi:10.1007/BF01910970 between pustular psoriasis subtypes. J Allergy Clin Immunol. 2. Navarini AA, Burden AD, Capon F, et al. European consensus state- 2019;143(3):1021–1026. doi:10.1016/j.jaci.2018.06.038 ment on phenotypes of pustular psoriasis. J Eur Acad Dermatol 19. Brenner M, Molin S, Ruebsam K, Weisenseel P, Ruzicka T, Prinz JC. Venereol. 2017;31(11):1792–1799. doi:10.1111/jdv.14386 Generalized pustular psoriasis induced by systemic glucocorticoster- 3. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF. oids: four cases and recommendations for treatment. Br J Dermatol. Clinical profile, morbidity, and outcome of adult-onset generalized 2009;161:964–966. doi:10.1111/j.1365-2133.2009.09348.x pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in 20. Westphal DC, Schettini AP, Souza PP, Castiel J, Chirano CA, Johor, Malaysia. Int J Dermatol. 2014;53(6):676–684. doi:10.1111/ Santos M. Generalized pustular psoriasis induced by systemic steroid ijd.12070 dose reduction. An Bras Dermatol. 2016;91(5):664–666. doi:10.1590/ 4. Ito T, Takahashi H, Kawada A, Iizuka H, Nakagawa H. abd1806-4841.20163804 Epidemiological survey from 2009 to 2012 of psoriatic patients in 21. Sugiura K, Shoda Y, Akiyama M. Generalized pustular psoriasis trig- Japanese Society for Psoriasis Research. J Dermatol. 2018;45 gered by amoxicillin in monozygotic twins with compound heterozy- (3):293–301. doi:10.1111/1346-8138.14105 gous IL36RN mutations: comment on the article by Navarini et al. 5. Griffiths CE, Christophers E, Barker JN, et al. A classification of JInvest Dermatol. 2014;134(2):578–579. doi:10.1038/jid.2013.354 psoriasis vulgaris according to phenotype. Br J Dermatol. 2007;156 22. Ozturk G, Turk BG, Karaca N, et al. Generalized pustular eruptions (2):258–262. doi:10.1111/j.1365-2133.2006.07675.x due to terbinafine. Cutan Ocul Toxicol. 2012;31(1):81–84. 6. Benjegerdes KE, Hyde K, Kivelevitch D, Mansouri B. Pustular psor- doi:10.3109/15569527.2011.607202 iasis: pathophysiology and current treatment perspectives. Psoriasis (Auckl). 2016;6:131–144. doi:10.2147/PTT.S98954 23. Tobin AM, Langan SM, Collins P, Kirby B. Generalized pustular 7. Raychaudhuri SK, Maverakis E, Raychaudhuri SP. Diagnosis and psoriasis (von Zumbusch) following the use of calcipotriol and beta- classification of psoriasis. Autoimmun Rev. 2014;13(4–5):490–495. methasone dipropionate ointment: a report of two cases. Clin Exp doi:10.1016/j.autrev.2014.01.008 Dermatol. 2009;34:629–630. doi:10.1111/j.1365-2230.2008.03034.x submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 41 DovePress Ly et al Dovepress 24. Hay RA, Pan JY. Paradoxical flare of pustular psoriasis triggered by 37. Umezawa Y, Ozawa A, Kawasima T, et al. Therapeutic guidelines for ustekinumab, which responded to adalimumab therapy. Clin Exp the treatment of generalized pustular psoriasis (GPP) based on Dermatol. 2014;39(6):751–752. doi:10.1111/ced.12392 a proposed classification of disease severity. Arch Dermatol Res. 25. Goiriz R, Dauden E, Perez-Gala S, Guhl G, Garcia-Diez A. Flare and 2003;295(Suppl 1):S43–S54. doi:10.1007/s00403-002-0371-6 change of psoriasis morphology during the course of treatment with 38. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological tumour necrosis factor blockers. Clin Exp Dermatol. 2007;32 spectrum of acute generalized exanthematous pustulosis (AGEP) and (2):176–179. doi:10.1111/j.1365-2230.2006.02315.x its differentiation from generalized pustular psoriasis. J Cutan Pathol. 26. Gregoriou S, Kazakos C, Christofidou E, Kontochristopoulos G, 2010;37(12):1220–1229. doi:10.1111/j.1600-0560.2010.01612.x Vakis G, Rigopoulos D. Pustular psoriasis development after initial 39. Sugiura K. The genetic background of generalized pustular psoriasis: ustekinumab administration in chronic plaque psoriasis. Eur IL36RN mutations and CARD14 gain-of-function variants. J Dermatol. 2011;21(1):104–105. doi:10.1684/ejd.2011.1164 J Dermatol Sci. 2014;74(3):187–192. doi:10.1016/j. 27. Georgala S, Koumantaki E, Rallis E, Papadavid E. Generalized jdermsci.2014.02.006 pustular psoriasis developing during withdrawal of short-term cyclos- 40. Diaz A. Deficiency of the Interleukin-36 Receptor Antagonist porin therapy. Br J Dermatol. 2000;142:1057–1058. (DITRA) and generalized pustular psoriasis. In: Efthimiou P, editor. 28. Maiolo C, Kwok SM, Ross C, Ibbetson J. Perianal streptococcal Auto-Inflammatory Syndromes: Pathophysiology, Diagnosis, and infection precipitating pustular psoriasis in an adult. JAAD Case Management. Cham: Springer International Publishing; 2019:85–94. Reports. 2016;2(4):281. doi:10.1016/j.jdcr.2016.05.010 41. Szatkowski J, Schwartz RA. Acute generalized exanthematous pus- 29. Feily A, Namazi MR, Seifmanesh H. Generalized pustular tulosis (AGEP): a review and update. J Am Acad Dermatol. 2015;73 psoriasis-like dermatophytosis due to Trichophyton rubrum. Acta (5):843–848. doi:10.1016/j.jaad.2015.07.017 Dermatovenerol Croat. 2011;19(3):209–211. 42. Mahil SK, Barker JN, Capon F. Pustular forms of psoriasis related to 30. Yoneda K, Matsuoka-Shirahige Y, Demitsu T, Kubota Y. Pustular autoinflammation. In: Hashkes PJ, Laxer RM, Simon A, editors. psoriasis precipitated by cytomegalovirus infection. Br J Dermatol. Textbook of Autoinflammation. Cham: Springer International 2012;167(5):1186–1189. doi:10.1111/j.1365-2133.2012.11044.x Publishing; 2019:471–484. 31. Ali FR, Green R, McMullen E, Motta L, Judge MR. Cutaneous 43. Hussain S, Berki DM, Choon SE, et al. IL36RN mutations define cytomegalovirus complicating pustular psoriasis. Br J Dermatol. a severe autoinflammatory phenotype of generalized pustular 2014;171(3):670–671. doi:10.1111/bjd.13026 psoriasis. J Allergy Clin Immunol. 2015;135(4):1067–1070.e1069. 32. Jiyad Z, Moriarty B, Creamer D, Higgins E. Generalized pustular doi:10.1016/j.jaci.2014.09.043 psoriasis associated with Epstein-Barr virus. Clin Exp Dermatol. 44. Mossner R, Wilsmann-Theis D, Oji V, et al. The genetic basis for 2015;40(2):146–148. doi:10.1111/ced.12493 most patients with pustular skin disease remains elusive. Br 33. Sugiura K, Uchiyama R, Okuyama R, Akiyama M. Varicella zoster J Dermatol. 2018;178(3):740–748. doi:10.1111/bjd.15867 virus-associated generalized pustular psoriasis in a baby with hetero- 45. Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor zygous IL36RN mutation. J Am Acad Dermatol. 2014;71(5):e216– antagonist deficiency and generalized pustular psoriasis. The New e218. doi:10.1016/j.jaad.2014.07.015 England Journal of Medicine. 2011;365(7):620–628. doi:10.1056/ 34. Kawamura A, Kinoshita MT, Suzuki H. Generalized pustular psor- NEJMoa1013068 iasis with hypoparathyroidism. Eur J Dermatol. 1999;9(7):574–576. 46. Navarini AA, Simpson MA, Borradori L, Yawalkar N, Schlapbach C. 35. George L, Mathews V, George B, Thomas M, Pulimood SA. Homozygous missense mutation in IL36RN in generalized pustular Generalized pustular psoriasis following allogeneic stem cell dermatosis with intraoral involvement compatible with both AGEP transplantation. Clin Exp Dermatol. 2015;40(2):160–162. and generalized pustular psoriasis. JAMA Dermatol. 2015;151 doi:10.1111/ced.12508 (4):452–453. doi:10.1001/jamadermatol.2014.3848 36. Deng W, Miao C, Zhang X. Abrupt generalized pustules in patients with rheumatoid arthritis and interstitial lung disease. J Dermatol. 2018;45(2):198–201. doi:10.1111/1346-8138.14126 Psoriasis: Targets and Therapy Dovepress Publish your work in this journal Psoriasis: Targets and Therapy is international, peer-reviewed, open optimal use of integrated treatment interventions to achieve access journal focusing on psoriasis, nail psoriasis, psoriatic arthritis improved outcomes and quality of life. Visit http://www.dovepress. and related conditions, identification of therapeutic targets and the com/testimonials.php to read real quotes from published authors. Submit your manuscript here: http://www.dovepress.com/psoriasis-targets-and-therapy-journal submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 DovePress http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psoriasis: Targets and Therapy Pubmed Central

Diagnosis and screening of patients with generalized pustular psoriasis

Psoriasis: Targets and Therapy , Volume 9 – Jun 20, 2019

Loading next page...
 
/lp/pubmed-central/diagnosis-and-screening-of-patients-with-generalized-pustular-40Ix4YCmDe

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
Pubmed Central
Copyright
© 2019 Ly et al.
ISSN
2230-326X
eISSN
2230-326X
DOI
10.2147/PTT.S181808
Publisher site
See Article on Publisher Site

Abstract

Psoriasis: Targets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article REV I EW Diagnosis and screening of patients with generalized pustular psoriasis This article was published in the following Dove Press journal: Psoriasis: Targets and Therapy Abstract: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening Karen Ly* variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular Kristen M Beck* eruptions on inflamed, erythematous skin. It is important to recognize acute GPP as a subtype Mary P Smith of psoriasis associated with high morbidity and mortality so therapy can be initiated without Quinn Thibodeaux delay. Since GPP was first described in 1910 by Leopold von Zumbusch, it has been Tina Bhutani inconsistently defined, stratified, and diagnosed in the literature. Multiple definitions and Department of Dermatology, University diagnostic criteria have been proposed over the years. Recently, formal consensus guidelines of California, San Francisco, CA, USA on GPP have been published by international groups. This article reviews the current *These authors contributed equally to evidence and understanding in the diagnosis and screening of GPP. this work Keywords: generalized pustular psoriasis, acute generalized pustular psoriasis of von Zumbusch, pustular psoriasis, diagnostic criteria Introduction Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life- threatening variant of psoriasis that is characterized by recurrent, acute onset, widely distributed pustular eruptions on inflamed, erythematous skin. Prompt diagnosis of GPP may prevent morbidity from complications including sepsis, acute renal failure, high-output congestive heart failure, and acute respiratory distress syndrome. This article reviews the current evidence and understanding in the diagnosis and screening of GPP. Background In contrast to chronic plaque psoriasis, which accounts for the majority of psoriasis vulgaris (PV) cases worldwide, GPP is considered to be a rare disease. A 2018 Japanese epidemiological analysis reported that GPP represented just 1.8% of all clinical types of psoriasis. However, the exact prevalence of GPP is unknown. One reason for this is that since its first description in 1910 by Leopold von Zumbusch, it has been inconsistently defined, stratified, and diagnosed in the literature. Rigorous studies characterizing GPP have been limited by both the rarity of the disease and by multiple definitions and diagnostic criteria that have been proposed over the years. Historically, pustular psoriasis has been classified as either generalized or Correspondence: Kristen M Beck Department of Dermatology, University localized. The generalized forms are then further stratified by the acuity of pre- of California, 515 Spruce Street, San sentation, acute GPP (also known as GPP, generalized pustular psoriasis of von Francisco, CA 94118, USA Tel +1 415 476 4701 Zumbusch, or von Zumbusch type GPP) and subacute GPP (also known as annular Fax +1 415 502 4126 5–7 Email Kristen.beck@ucsf.edu pustular psoriasis (APP) or annular pattern GPP). submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 37–42 37 DovePress © 2019 Ly et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work http://doi.org/10.2147/PTT.S181808 you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Ly et al Dovepress Acute onset GPP is the most common type, which GPP is also reported to occur at a higher incidence in 3,8 16,18 accounts for more than two-thirds of GPP cases. When women. acute GPP occurs in pregnancy, it is often termed impetigo Although many cases appear to be idiopathic, medica- herpetiformis (IH). Juvenile pustular psoriasis (JPP) is tions, infections, and pregnancy have been reported as 9,10 3,8,12 a subtype of GPP that occurs in the pediatric population. triggers of GPP. A detailed drug history is important Although some studies have included APP as a variant as it can associate the initiation or withdrawal of a drug 3,7 of GPP, this is controversial due to its subacute course and with the onset of disease. Rapid tapering of systemic mild systemic symptoms. Subacute GPP is characterized corticosteroids is a well-known and frequently reported 19,20 by annular lesions with pustules, erythema, and scaling at trigger for GPP flares. Many other medications have 3,11,12 the advancing edge. Patients typically lack systemic also been implicated as a trigger, including antibiotics such 21 22 23 symptoms and laboratory abnormalities. as amoxicillin, terbinafine, calcipotriol ointment, GPP is also distinguished from the transient, primary betamethasone ointment, tumor necrosis factor-alpha 24,25 24,26 pustule formation that may occur at the periphery of psor- (TNF-α) inhibitors, ustekinumab, and withdrawal iasis plaques in PV. This may occur in patients with PV of cyclosporine. during periods of disease exacerbation or following the Infections reported as potential etiological factors in 28 29 application of irritants, such as tars. Although this phenom- GPP include streptococcal, Trichophyton rubrum, 30,31 32 enon has been termed “localized GPP” and “psoriasis cum cytomegalovirus, Epstein-Barr virus, and vari- 2 33 pustulatione” (psoriasis with pustules), it is generally recog- cella-zoster virus. GPP has also been associated with nized that it is not a type of pustular psoriasis. various medical conditions including Turner syndrome, 34 34 hypoparathyroidism, hypocalcemia, allogeneic stem 35 36 Clinical diagnosis cell transplantation, rheumatoid arthritis, and The diagnosis of GPP should be suspected in patients with cardiomyopathy. acute onset erythema and pustulosis, and subsequently On initial evaluation, it is important to determine evaluated using clinicopathologic correlation between which patients require immediate hospitalization due to physical examination findings, patient history, review of risk of complication. Systemic symptoms including fever, symptoms, and histopathology. chills, shortness of breath, and altered mental status may GPP presents as the rapid onset of widespread, erythema- indicate the need for inpatient admission. Obtaining tous, inflamed skin studded with 2- to 3-mm sterile pustules. a history of comorbid medical conditions may also help Pustules may expand and coalesce into irregular “lakes of triage patients who are at higher risk for complications. pus.” During episodes of pustulation, patients may develop These include advanced age, congestive heart failure, renal abnormal clinical findings associated with systemic inflamma- insufficiency, diabetes mellitus, or immunodeficiency. Patients with GPP may develop life-threatening com- tion. Patients appear systemically ill, with high-grade fever, 8,11,12 plications, including sepsis, acute renal failure, neutrophi- chills, malaise, and anorexia. Erythroderma may occur. lic cholangitis, high-output congestive heart failure, acute After 1–2 days, the pustules typically resolve with residual 3 3,8 respiratory distress syndrome, and death. Mortality in erythema and desquamation. GPP is most commonly due to complications from sepsis, A physical examination of the skin and oral mucosa is 3,17 acute respiratory distress syndrome, and cardiac failure. important to evaluate the extent of skin involvement. Associated cutaneous symptoms may include pain, burn- It is therefore critical to identify which patients require ing, and pruritus. Associated mucosal findings include hospitalization for stabilization, rapid treatment, and to a geographic or fissured tongue, cheilitis, and ocular invol- reduce morbidity and mortality. 3,13 vement (eg, conjunctivitis, uveitis, iritis). Additional There is no cure for GPP. GPP may be relapsing, with extracutaneous findings may include nail abnormalities, recurrence either idiopathic or only when exposed to a trigger, 15,16 arthralgias, jaundice, and lower extremity edema. or persistent, with symptoms lasting for months. Symptoms A history of concurrent or previous PV may be helpful in may self-resolve or require aggressive treatment. confirming the diagnosis; however, not all patients have a history of psoriasis. GPP may occur with or without Laboratory abnormalities 3,17,18 ahistoryof PV. GPP may affect patients at any age, Laboratory evaluations are strongly recommended and 3,13,16 but most commonly affects patients in the fourth decade. deemed necessary to assess for severity and potential submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 DovePress Dovepress Ly et al due to medications. complications associated with GPP. Laboratory abnormalities It presents as sterile pustules on an would be consistent with the systemic involvement seen in erythematous base and can be clinically and histologically GPP, the most common of which are leukocytosis with neu- difficult to differentiate from GPP. Clinically, AGEP has trophilia and elevated erythrocyte sedimentation rate (ESR). a more abrupt onset, shorter duration, does not recur, has Complete blood count with differential (to evaluate for leuko- no personal or family history of PV, and is associated with 38,41 cytosis and lymphopenia) and a comprehensive metabolic a recently initiated medication. AGEP may also be panel (to evaluate for hypocalcemia, other electrolyte abnorm- accompanied by blood eosinophilia. alities, hypoalbuminemia, and to evaluate liver and renal func- tion) are common initial assessments. Skin desquamation and Genetic screening epidermal barrier disruption may result in electrolyte abnorm- Although the etiology of GPP remains to be fully eluci- alities. Hypocalcemia can occur as a result of hypoalbumine- dated, a genetic basis that may cause or contribute to mia, but ionized calcium is typically normal and patients are pustular variants of psoriasis, distinct from that of chronic 8,12 asymptomatic. Patients may have increased alkaline phos- plaque psoriasis, has been identified. 6,8 phatase, transaminase, and bilirubin levels. Patient who In recent years, genetic studies have identified three report an antecedent upper respiratory infection may have gene mutations in one or more forms of pustular psoriasis- positive anti-streptolysin titers. mutations in IL36RN (encodes IL-36 receptor antagonist), Cultures of pustules and blood samples, gram stains, CARD14 (encodes a keratinocyte adaptor protein), and and potassium hydroxide preparation can also be per- AP1S3 (encodes a subunit of the adaptor protein 1 com- formed to rule out other causes of pustulosis. plex). These three mutations account for fewer than 30% of GPP cases. IL36RN mutations are the most frequent genetic abnormality observed in pustular psoriasis and Histopathology 38 occur in approximately 20% of GPP patients. AP1S3 Skin biopsy is important to confirm the diagnosis of GPP. and CARD14 variants are found in fewer than 10% of The histopathology of GPP is characterized by Kogoj’s spon- these patients. giform pustules, which are the accumulations of neutrophils Currently, genetic screenings for IL36RN, CARD14, under the stratum corneum, as well as the classic findings of and AP1S3 mutations are not routinely indicated. psoriasis, which include parakeratosis, acanthosis, hyperkera- However, IL36RN mutations are being increasingly used tosis, elongation of rete ridges, diminished stratum granulo- to aid in the diagnosis of GPP. Genotype–phenotype stu- sum, capillary dilation of the papillary dermis, Munro’s dies have shown that IL36RN mutations are associated microabscesses, and superficial perivascular mononuclear with an earlier age of onset in GPP, widespread inflamma- cell infiltrations. The edema and inflammatory cell infiltrate 18,43,44 11,37–39 tion, and are not associated with concurrent PV. is notably greater than what is observed in PV. When this clinical triad is present in familial IL36RN Other diseases with similar histopathology include mutations, it is described by the acronym DITRA (defi- acute generalized exanthematous pustulosis (AGEP). ciency of the interleukin 36 receptor antagonist). However, the additional presence of eosinophils and Twelves et al demonstrated that IL36RN mutations were necrotic keratinocytes, which are suggestive of an under- 40 associated with an earlier age of onset across all pustular lying drug trigger, would likely be seen. psoriasis subtypes, with the youngest age of onset found in GPP patients (mean age of onset 31 years ±19.7 years). Differential diagnosis Based on this finding, this study recommended that The list of differential diagnoses for GPP is vast and patients who present with GPP before age 30 be screened includes many cutaneous pustular diseases, including for IL36RN mutations. AGEP, subacute annular pustular psoriasis (APP), loca- lized forms of pustular psoriasis (eg, palmoplantar pustular Proposed diagnostic criteria psoriasis, Acrodermatitis continua of Hallopeau), pemphi- Recent consensus guidelines on GPP have been published gus foliaceus, IgA pemphigus, and subcorneal pustular by European and Japanese groups in order to distinguish 11,38 dermatosis. GPP from other pustular diseases (Table 1). One goal of The most important diagnosis to exclude is AGEP, these guidelines is to develop an extended cohort using a rare and severe pustular skin reaction, most commonly standard classification in order to reveal clinical and genetic submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 39 DovePress Ly et al Dovepress Table 1 Summary of diagnostic criteria persisted for more than three months. No severity assess- ment was published with this report. However, ERASPEN Year Diagnostic Criteria did acknowledge the need for updated severity criteria. It Umezawa et al 2003 1. Systemic symptoms such as fever was thought that using the number of pustules present to and malaise measure severity would be limited by the diverse morphol- 2. Multiple, isolated septic pustules on ogy of GPP, which may include either discrete or confluent erythematous skin 3. Kogoj’s spongiform pustules are his- pustules. If a patient presents with mixed types of pustular topathologically confirmed psoriasis (eg, both GPP and a localized form of pustular 4. Laboratory abnormalities, including psoriasis, such as Arodermatitis continua of Hallopeau), left shift leukocytosis, elevated ESR, then the patient should be classified according to the most elevated C-reactive protein (CRP), predominant feature. elevated anti-streptolysin O antibody The Japanese guideline was published in 2018 by the levels, elevated IgG or IgA, hypopro- teinemia, hypocalcemia Japanese Dermatological Association and the Study Group 5. Recurrence of these clinical and for Rare Intractable Skin Diseases as an update to histological findings 37 Umezawa et al’s 2003 GPP guideline. This guideline Navarini et al 2017 Primary, sterile, macroscopically visible by Fujita et al defines GPP as a rare disease in which epidermal pustules on non-acral skin acute fever, generalized skin rashes, and many sterile Subclassifiers pustules develop. Histopathologically, GPP forms subcor- 1. With or without systemic inflam- mation neal pustules characterized by Kogoj’s spongiform pus- 2. With or without plaque psoriasis tules. GPP may or may not be preceded by PV and is 3. Either relapsing (>1 episode) or characterized by repeated disease recurrence. During the persistent (>3 months) course of the disease, patients have abnormal clinical Fujita et al 2018 1. Systemic symptoms such as fever findings associated with systemic inflammation and often and fatigue present with mucosal symptoms and arthritis as complica- 2. Systemic or extensive flush accom- panied by multiple sterile pustules tions. Although rare, GPP may be accompanied by certain 3. Neutrophilic subcorneal pustules eye symptoms and secondary amyloidosis. histopathologically characterized by Fujita et al made a few important additions to the defini- Kogoj’s spongiform pustules tion of GPP. The definition was updated to include that GPP 4. Recurrence of these clinical and may have potential complications of arthritis, mucosal and histological findings ocular symptoms, and secondary amyloidosis. This addition Adefinitive diagnosis of GPP can be made in patients with all 4 features. to the definition was made to emphasize that GPP involves GPP would be suspected in those with more than just skin lesions, it causes systemic inflammation features 2 and 3. and has the potential for serious complications. Another Abbreviations: ESR, erythrocyte sedimentation rate; GPP, generalized pustular significant difference between the 2003 and 2018 Japanese psoriasis. criteria was the removal of laboratory abnormalities from the criteria. This was due to insufficient sensitivity and specifi- insights into patient demographics, clinical features, and city of laboratory abnormalities in the diagnosis of GPP; genetic mutations that may improve diagnosis and early instead, laboratory abnormalities were strongly recom- treatment of this potentially life-threatening disease. mended and deemed necessary to assess for severity and In 2017, the European Rare and Severe Psoriasis potential complications (Table 2). Expert Network (ERASPEN) published the first European consensus statement on the phenotypes of pust- Conclusion ular psoriasis. GPP was defined as primary, sterile, macro- The diagnosis of GPP can be challenging due to its rarity, scopically visible pustules on non-acral skin. In addition to heterogeneous presentation, and lack of consistent classi- this, the criteria included subclassifiers that indicate if GPP fication, but it is important to recognize acute GPP as occurs with or without PV and with or without systemic a potentially fatal subtype of psoriasis so therapy can be inflammation. The criteria also specify that a diagnosis of initiated without delay. GPP is diagnosed based on the GPP can only be made when the condition has relapsed or presence of visible pustules on erythematous skin with submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 DovePress Dovepress Ly et al Table 2 Summary of assessments included in criteria Systemic symptoms Pustules Histology Laboratory abnormalities Recurrence PV Umezawa et al ++ + + + − Navarini et al ±+ −− +± Fujita et al ++ + − + − Notes: + indicates present; ± indicates present or absent; - indicates absent. Abbreviation: PV, psoriasis vulgaris. 8. Borges-Costa J, Silva R, Goncalves L, Filipe P, Soares de Almeida L, confirmation from histopathology, and supportive evidence Marques Gomes M. Clinical and laboratory features in acute generalized from laboratory and genetic evaluations. The most impor- pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol. tant diagnosis to exclude is AGEP. 2011;12(4):271–276. doi:10.2165/11586900-000000000-00000 9. de Oliveira ST, Maragno L, Arnone M, Fonseca Takahashi MD, Romiti R. These findings are reflected in recent consensus guide- Generalized pustular psoriasis in childhood. Pediatr Dermatol. 2010;27 lines by the ERASPEN and the Japanese Dermatological (4):349–354. doi:10.1111/j.1525-1470.2010.01084.x 2,14 10. Lau BW, Lim DZ, Capon F, Barker JN, Choon SE. Juvenile general- Association. Both guidelines share two features: the ized pustular psoriasis is a chronic recalcitrant disease: an analysis of clinical presence of pustules and disease recurrence. 27 patients seen in a tertiary hospital in Johor, Malaysia. Other requirements for diagnosis such as systemic inflam- Int J Dermatol. 2017;56(4):392–399. doi:10.1111/ijd.13489 11. Naik HB, Cowen EW. Autoinflammatory pustular neutrophilic mation, Kogoj’s spongiform pustules, and laboratory diseases. Dermatol Clin. 2013;31(3):405–425. doi:10.1016/j. 14,37,46 abnormalities vary depending on the criteria used. det.2013.04.001 12. Baker H, Ryan TJ. Generalized pustular psoriasis. A clinical and These diagnostic criteria can be utilized for the assessment epidemiological study of 104 cases. Br J Dermatol. 1968;80 and diagnosis of GPP, but there remains a need for (12):771–793. a unified diagnostic criteria that can be universally adopted 13. Jin H, Cho HH, Kim WJ, et al. Clinical features and course of generalized pustular psoriasis in Korea. J Dermatol. 2015;42 and allow for further characterization of GPP in larger (7):674–678. doi:10.1111/1346-8138.12863 cohorts. Further genetic studies are needed to determine 14. Fujita H, Terui T, Hayama K, et al. Japanese guidelines for the management and treatment of generalized pustular psoriasis: the the clinical significance of known genetic mutations in the new pathogenesis and treatment of GPP. J Dermatol. 2018;45 classification, diagnosis, and screening of GPP. (11):1235–1270. doi:10.1111/1346-8138.14523 15. Viguier M, Allez M, Zagdanski AM, et al. High frequency of cho- lestasis in generalized pustular psoriasis: evidence for neutrophilic Disclosure involvement of the biliary tract. Hepatology. 2004;40(2):452–458. doi:10.1002/hep.20305 The authors report no conflicts of interest in this work. 16. Tay YK, Tham SN. The profile and outcome of pustular psoriasis in Singapore: a report of 28 cases. Int J Dermatol. 1997;36(4):266–271. 17. Hoegler KM, John AM, Handler MZ, Schwartz RA. Generalized References pustular psoriasis: a review and update on treatment. J Eur Acad Dermatol Venereol. 2018;32(10):1645–1651. doi:10.1111/jdv.14949 1. Zumbusch V. Leopold. Psoriasis and pustuloses Exanthem. Arch 18. Twelves S, Mostafa A, Dand N, et al. Clinical and genetic differences Dermatol Syphilol. 1910;99:335–346. doi:10.1007/BF01910970 between pustular psoriasis subtypes. J Allergy Clin Immunol. 2. Navarini AA, Burden AD, Capon F, et al. European consensus state- 2019;143(3):1021–1026. doi:10.1016/j.jaci.2018.06.038 ment on phenotypes of pustular psoriasis. J Eur Acad Dermatol 19. Brenner M, Molin S, Ruebsam K, Weisenseel P, Ruzicka T, Prinz JC. Venereol. 2017;31(11):1792–1799. doi:10.1111/jdv.14386 Generalized pustular psoriasis induced by systemic glucocorticoster- 3. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF. oids: four cases and recommendations for treatment. Br J Dermatol. Clinical profile, morbidity, and outcome of adult-onset generalized 2009;161:964–966. doi:10.1111/j.1365-2133.2009.09348.x pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in 20. Westphal DC, Schettini AP, Souza PP, Castiel J, Chirano CA, Johor, Malaysia. Int J Dermatol. 2014;53(6):676–684. doi:10.1111/ Santos M. Generalized pustular psoriasis induced by systemic steroid ijd.12070 dose reduction. An Bras Dermatol. 2016;91(5):664–666. doi:10.1590/ 4. Ito T, Takahashi H, Kawada A, Iizuka H, Nakagawa H. abd1806-4841.20163804 Epidemiological survey from 2009 to 2012 of psoriatic patients in 21. Sugiura K, Shoda Y, Akiyama M. Generalized pustular psoriasis trig- Japanese Society for Psoriasis Research. J Dermatol. 2018;45 gered by amoxicillin in monozygotic twins with compound heterozy- (3):293–301. doi:10.1111/1346-8138.14105 gous IL36RN mutations: comment on the article by Navarini et al. 5. Griffiths CE, Christophers E, Barker JN, et al. A classification of JInvest Dermatol. 2014;134(2):578–579. doi:10.1038/jid.2013.354 psoriasis vulgaris according to phenotype. Br J Dermatol. 2007;156 22. Ozturk G, Turk BG, Karaca N, et al. Generalized pustular eruptions (2):258–262. doi:10.1111/j.1365-2133.2006.07675.x due to terbinafine. Cutan Ocul Toxicol. 2012;31(1):81–84. 6. Benjegerdes KE, Hyde K, Kivelevitch D, Mansouri B. Pustular psor- doi:10.3109/15569527.2011.607202 iasis: pathophysiology and current treatment perspectives. Psoriasis (Auckl). 2016;6:131–144. doi:10.2147/PTT.S98954 23. Tobin AM, Langan SM, Collins P, Kirby B. Generalized pustular 7. Raychaudhuri SK, Maverakis E, Raychaudhuri SP. Diagnosis and psoriasis (von Zumbusch) following the use of calcipotriol and beta- classification of psoriasis. Autoimmun Rev. 2014;13(4–5):490–495. methasone dipropionate ointment: a report of two cases. Clin Exp doi:10.1016/j.autrev.2014.01.008 Dermatol. 2009;34:629–630. doi:10.1111/j.1365-2230.2008.03034.x submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 41 DovePress Ly et al Dovepress 24. Hay RA, Pan JY. Paradoxical flare of pustular psoriasis triggered by 37. Umezawa Y, Ozawa A, Kawasima T, et al. Therapeutic guidelines for ustekinumab, which responded to adalimumab therapy. Clin Exp the treatment of generalized pustular psoriasis (GPP) based on Dermatol. 2014;39(6):751–752. doi:10.1111/ced.12392 a proposed classification of disease severity. Arch Dermatol Res. 25. Goiriz R, Dauden E, Perez-Gala S, Guhl G, Garcia-Diez A. Flare and 2003;295(Suppl 1):S43–S54. doi:10.1007/s00403-002-0371-6 change of psoriasis morphology during the course of treatment with 38. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological tumour necrosis factor blockers. Clin Exp Dermatol. 2007;32 spectrum of acute generalized exanthematous pustulosis (AGEP) and (2):176–179. doi:10.1111/j.1365-2230.2006.02315.x its differentiation from generalized pustular psoriasis. J Cutan Pathol. 26. Gregoriou S, Kazakos C, Christofidou E, Kontochristopoulos G, 2010;37(12):1220–1229. doi:10.1111/j.1600-0560.2010.01612.x Vakis G, Rigopoulos D. Pustular psoriasis development after initial 39. Sugiura K. The genetic background of generalized pustular psoriasis: ustekinumab administration in chronic plaque psoriasis. Eur IL36RN mutations and CARD14 gain-of-function variants. J Dermatol. 2011;21(1):104–105. doi:10.1684/ejd.2011.1164 J Dermatol Sci. 2014;74(3):187–192. doi:10.1016/j. 27. Georgala S, Koumantaki E, Rallis E, Papadavid E. Generalized jdermsci.2014.02.006 pustular psoriasis developing during withdrawal of short-term cyclos- 40. Diaz A. Deficiency of the Interleukin-36 Receptor Antagonist porin therapy. Br J Dermatol. 2000;142:1057–1058. (DITRA) and generalized pustular psoriasis. In: Efthimiou P, editor. 28. Maiolo C, Kwok SM, Ross C, Ibbetson J. Perianal streptococcal Auto-Inflammatory Syndromes: Pathophysiology, Diagnosis, and infection precipitating pustular psoriasis in an adult. JAAD Case Management. Cham: Springer International Publishing; 2019:85–94. Reports. 2016;2(4):281. doi:10.1016/j.jdcr.2016.05.010 41. Szatkowski J, Schwartz RA. Acute generalized exanthematous pus- 29. Feily A, Namazi MR, Seifmanesh H. Generalized pustular tulosis (AGEP): a review and update. J Am Acad Dermatol. 2015;73 psoriasis-like dermatophytosis due to Trichophyton rubrum. Acta (5):843–848. doi:10.1016/j.jaad.2015.07.017 Dermatovenerol Croat. 2011;19(3):209–211. 42. Mahil SK, Barker JN, Capon F. Pustular forms of psoriasis related to 30. Yoneda K, Matsuoka-Shirahige Y, Demitsu T, Kubota Y. Pustular autoinflammation. In: Hashkes PJ, Laxer RM, Simon A, editors. psoriasis precipitated by cytomegalovirus infection. Br J Dermatol. Textbook of Autoinflammation. Cham: Springer International 2012;167(5):1186–1189. doi:10.1111/j.1365-2133.2012.11044.x Publishing; 2019:471–484. 31. Ali FR, Green R, McMullen E, Motta L, Judge MR. Cutaneous 43. Hussain S, Berki DM, Choon SE, et al. IL36RN mutations define cytomegalovirus complicating pustular psoriasis. Br J Dermatol. a severe autoinflammatory phenotype of generalized pustular 2014;171(3):670–671. doi:10.1111/bjd.13026 psoriasis. J Allergy Clin Immunol. 2015;135(4):1067–1070.e1069. 32. Jiyad Z, Moriarty B, Creamer D, Higgins E. Generalized pustular doi:10.1016/j.jaci.2014.09.043 psoriasis associated with Epstein-Barr virus. Clin Exp Dermatol. 44. Mossner R, Wilsmann-Theis D, Oji V, et al. The genetic basis for 2015;40(2):146–148. doi:10.1111/ced.12493 most patients with pustular skin disease remains elusive. Br 33. Sugiura K, Uchiyama R, Okuyama R, Akiyama M. Varicella zoster J Dermatol. 2018;178(3):740–748. doi:10.1111/bjd.15867 virus-associated generalized pustular psoriasis in a baby with hetero- 45. Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor zygous IL36RN mutation. J Am Acad Dermatol. 2014;71(5):e216– antagonist deficiency and generalized pustular psoriasis. The New e218. doi:10.1016/j.jaad.2014.07.015 England Journal of Medicine. 2011;365(7):620–628. doi:10.1056/ 34. Kawamura A, Kinoshita MT, Suzuki H. Generalized pustular psor- NEJMoa1013068 iasis with hypoparathyroidism. Eur J Dermatol. 1999;9(7):574–576. 46. Navarini AA, Simpson MA, Borradori L, Yawalkar N, Schlapbach C. 35. George L, Mathews V, George B, Thomas M, Pulimood SA. Homozygous missense mutation in IL36RN in generalized pustular Generalized pustular psoriasis following allogeneic stem cell dermatosis with intraoral involvement compatible with both AGEP transplantation. Clin Exp Dermatol. 2015;40(2):160–162. and generalized pustular psoriasis. JAMA Dermatol. 2015;151 doi:10.1111/ced.12508 (4):452–453. doi:10.1001/jamadermatol.2014.3848 36. Deng W, Miao C, Zhang X. Abrupt generalized pustules in patients with rheumatoid arthritis and interstitial lung disease. J Dermatol. 2018;45(2):198–201. doi:10.1111/1346-8138.14126 Psoriasis: Targets and Therapy Dovepress Publish your work in this journal Psoriasis: Targets and Therapy is international, peer-reviewed, open optimal use of integrated treatment interventions to achieve access journal focusing on psoriasis, nail psoriasis, psoriatic arthritis improved outcomes and quality of life. Visit http://www.dovepress. and related conditions, identification of therapeutic targets and the com/testimonials.php to read real quotes from published authors. Submit your manuscript here: http://www.dovepress.com/psoriasis-targets-and-therapy-journal submit your manuscript | www.dovepress.com Psoriasis: Targets and Therapy 2019:9 DovePress

Journal

Psoriasis: Targets and TherapyPubmed Central

Published: Jun 20, 2019

References