An 8-year-old girl with a 4-year history of chronic intermittent eruption of a pustular rash on her torso presented for evaluation in the dermatology clinic with an ongoing flare. The current rash had persisted despite the application of topical fluocinonide, topical clobetasol, a selenium sulfide wash, and oral cephalexin.
Physical Examination
Laboratory test findings were significant for a neutrophilic leukocytosis (14,200 white blood cells/µL). Histologic review of a punch biopsy specimen demonstrated an epidermal and superficial perivascular neutrophilic infiltrate with overlying serum crust. Results of Grocott methenamine silver and periodic acid–Schiff stains were unremarkable.
The results of further evaluation with a basic metabolic panel, serologic testing for hepatitis B, and purified protein derivative skin testing for tuberculosis were normal or negative. Based on her presentation and laboratory test results, the patient received a diagnosis of pustular psoriasis (Figures 1 and 2).
{{pagebreak}}
Treatment
A regimen of weekly subcutaneous etanercept (Enbrel) injections was initiated, which led to near complete resolution of the plaques over the course of several months without perceivable adverse effects.
Figure 3 shows the patient at 6-month follow-up.
Discussion
Pustular psoriasis is an uncommon variant of psoriasis that can develop independently or in association with preexisting psoriasis. The exact prevalence of generalized pustular psoriasis (GPP) is unknown. It is most often seen in middle-aged adults but can occur in children,1,2 as this patient’s case illustrates.
The development of pustular psoriasis has been linked to upper respiratory tract infection, pregnancy, withdrawal of corticosteroids, hypocalcemia, and the use of various medications, including interferon, lithium, penicillin, cyclosporine, salicylates, and tumor necrosis factor α (TNF-α) inhibitors.1,3-9 It is often observed in patients with a history of psoriasis.1,2
Pustular psoriasis is characterized by an acute, subacute, or chronic eruption of sterile pustules associated with erythema and inflammation. This patient’s case represents the annular variant (also called subacute GPP), characterized by pustules on the periphery of expanding erythematous plaques with central healing, most often localized to the trunk. The acute variant (also called von Zumbusch psoriasis) is characterized by the abrupt onset of numerous pustules on a background of widespread erythema with associated systemic symptoms such as fever, malaise, headache, nausea, arthralgia, and skin tenderness. The exanthematous type, acute generalized exanthematous pustulosis (AGEP) is precipitated by medications or infection and is usually not accompanied by systemic symptoms. The localized variant involves eruption of pustules on the palms, soles, fingertips, and/or nail beds.1,2
Laboratory analysis commonly demonstrates leukocytosis of up to 30,000 cells/µL, absolute lymphocytopenia, an elevated erythrocyte sedimentation rate, hypocalcemia, transaminitis, hypoalbuminemia, and/or an elevated antistreptolysin antibody level. Cultures of the pustules will usually not yield significant growth of pathogenic organisms unless superinfection is present.1 The diagnosis is solidified with skin biopsy findings, which commonly demonstrate classic psoriasiform changes, including parakeratosis and elongation of the rete ridges, along with an epidermal neutrophil infiltrate, upper dermal perivascular lymphocyte infiltrate, and intraspinous aggregates of neutrophils known as spongiform pustules of Kogoj.10
The differential diagnosis mainly includes dermatitis with secondary infection, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), IgA pemphigus, tinea corporis, and AGEP.11 Distinguishing GPP from AGEP can be challenging, because the clinical presentations are nearly identical. However, AGEP is more likely to be associated with antibiotic use.12 Biopsy findings that favor AGEP include a lack of significant psoriasiform changes, the presence of a mixed neutrophil-rich infiltrate, eosinophils and necrotic keratinocytes in the dermis, and lack of tortuous blood vessels.10
Patients with acute GPP may require hospitalization to ensure adequate supportive care. Causative drugs must be identified and discontinued. First-line systemic agents include acitretin, methotrexate, infliximab (Remicade), and cyclosporine.13 Topical therapies are used as adjuvants to systemic therapy. Systemic glucocorticoids can induce rapid improvement in GPP but have been identified as a potential precipitant.
A recent review comparing the efficacy and safety of biologic agents in the treatment of pediatric GPP concluded that etanercept should be considered before infliximab and adalimumab (Humira) as a first-line biologic agent due its comparatively favorable efficacy and safety profile.14 However, the eruption of lesions of pustular psoriasis has been associated with TNF-α inhibitors.15,16
Chief features of the disease are its tendency to recur and its persistence. The course of GPP is often associated with periods of quiescence and recurrence over the course of years. However, with therapy, flares may be avoided.1
Drs Peters and Ballin are with the United States Navy Medical Corps.
This article originally appeared in Consultant. 2017;57(8):493-497.
References
1. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF. Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol. 2014;53(6):676-684.
2. Borges-Costa J, Silva R, Gonçalves L, Filipe P, Soares de Almeida L, Marques Gomes M. Clinical and laboratory features in acute generalized pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol. 2011;12(4):271-276.
3. Georgala S, Koumantaki E, Rallis E, Papadavid E. Generalized pustular psoriasis developing during withdrawal of short-term cyclosporin therapy. Br J Dermatol. 2000;142(5):1057-1058.
4. Sugiura K, Shoda Y, Akiyama M. Generalized pustular psoriasis triggered by amoxicillin in monozygotic twins with compound heterozygous IL36RN mutations: comment on the article by Navarini et al. J Invest Dermatol. 2014;134(2):578-579.
5. Wu M-C, Lee J-Y. Generalized flare of pustular psoriasis induced by PEGylated interferon-α2b therapy for chronic hepatitis C. Australas J Dermatol. 2012;53(4):e69-e72.
6. Shmidt E, Wetter DA, Ferguson SB, Pittelkow MR. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol. 2012;67(5):e179-e185.
7. Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol. 2006;24(2):101-104.
8. Lowe NJ, Ridgway HB. Generalized pustular psoriasis precipitated by lithium carbonate. Arch Dermatol. 1978;114(12):1788-1789.
9. Katz M, Seidenbaum M, Weinrauch L. Penicillin-induced generalized pustular psoriasis. J Am Acad Dermatol. 1987;17(5 pt 2):918-920.
10. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010;37(12):1220-1229.
11. Kalb RE. Pustular psoriasis: pathogenesis, clinical manifestations, and diagnosis. UpToDate. https://www.uptodate.com/contents/pustular-psoriasis-pathogenesis-clinical-manifestations-and-diagnosis Updated December 30, 2016. Accessed July 19, 2017.
12. Duckworth L, Maheshwari MB, Thomson MA. A diagnostic challenge: acute generalized exanthematous pustulosis or pustular psoriasis due to terbinafine. Clin Exp Dermatol. 2012;37(1):24-27.
13. Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(2):279-288.
14. Collamer AN, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. Semin Arthritis Rheum. 2010;40(3):233-240.
15. Saikaly SK, Mattes M. Biologics and pediatric generalized pustular psoriasis: an emerging therapeutic trend. Cureus. 2016;8(6):e652.
16. Ephrem G, Jour G, Smith BL. Successful treatment of von Zumbusch generalized pustular psoriasis with cyclosporine after eruption post etanercept injection. J Med Liban. 2011;59(3):168-169.
An 8-year-old girl with a 4-year history of chronic intermittent eruption of a pustular rash on her torso presented for evaluation in the dermatology clinic with an ongoing flare. The current rash had persisted despite the application of topical fluocinonide, topical clobetasol, a selenium sulfide wash, and oral cephalexin.
Physical Examination
Laboratory test findings were significant for a neutrophilic leukocytosis (14,200 white blood cells/µL). Histologic review of a punch biopsy specimen demonstrated an epidermal and superficial perivascular neutrophilic infiltrate with overlying serum crust. Results of Grocott methenamine silver and periodic acid–Schiff stains were unremarkable.
The results of further evaluation with a basic metabolic panel, serologic testing for hepatitis B, and purified protein derivative skin testing for tuberculosis were normal or negative. Based on her presentation and laboratory test results, the patient received a diagnosis of pustular psoriasis (Figures 1 and 2).
{{pagebreak}}
Treatment
A regimen of weekly subcutaneous etanercept (Enbrel) injections was initiated, which led to near complete resolution of the plaques over the course of several months without perceivable adverse effects.
Figure 3 shows the patient at 6-month follow-up.
Discussion
Pustular psoriasis is an uncommon variant of psoriasis that can develop independently or in association with preexisting psoriasis. The exact prevalence of generalized pustular psoriasis (GPP) is unknown. It is most often seen in middle-aged adults but can occur in children,1,2 as this patient’s case illustrates.
The development of pustular psoriasis has been linked to upper respiratory tract infection, pregnancy, withdrawal of corticosteroids, hypocalcemia, and the use of various medications, including interferon, lithium, penicillin, cyclosporine, salicylates, and tumor necrosis factor α (TNF-α) inhibitors.1,3-9 It is often observed in patients with a history of psoriasis.1,2
Pustular psoriasis is characterized by an acute, subacute, or chronic eruption of sterile pustules associated with erythema and inflammation. This patient’s case represents the annular variant (also called subacute GPP), characterized by pustules on the periphery of expanding erythematous plaques with central healing, most often localized to the trunk. The acute variant (also called von Zumbusch psoriasis) is characterized by the abrupt onset of numerous pustules on a background of widespread erythema with associated systemic symptoms such as fever, malaise, headache, nausea, arthralgia, and skin tenderness. The exanthematous type, acute generalized exanthematous pustulosis (AGEP) is precipitated by medications or infection and is usually not accompanied by systemic symptoms. The localized variant involves eruption of pustules on the palms, soles, fingertips, and/or nail beds.1,2
Laboratory analysis commonly demonstrates leukocytosis of up to 30,000 cells/µL, absolute lymphocytopenia, an elevated erythrocyte sedimentation rate, hypocalcemia, transaminitis, hypoalbuminemia, and/or an elevated antistreptolysin antibody level. Cultures of the pustules will usually not yield significant growth of pathogenic organisms unless superinfection is present.1 The diagnosis is solidified with skin biopsy findings, which commonly demonstrate classic psoriasiform changes, including parakeratosis and elongation of the rete ridges, along with an epidermal neutrophil infiltrate, upper dermal perivascular lymphocyte infiltrate, and intraspinous aggregates of neutrophils known as spongiform pustules of Kogoj.10
The differential diagnosis mainly includes dermatitis with secondary infection, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), IgA pemphigus, tinea corporis, and AGEP.11 Distinguishing GPP from AGEP can be challenging, because the clinical presentations are nearly identical. However, AGEP is more likely to be associated with antibiotic use.12 Biopsy findings that favor AGEP include a lack of significant psoriasiform changes, the presence of a mixed neutrophil-rich infiltrate, eosinophils and necrotic keratinocytes in the dermis, and lack of tortuous blood vessels.10
Patients with acute GPP may require hospitalization to ensure adequate supportive care. Causative drugs must be identified and discontinued. First-line systemic agents include acitretin, methotrexate, infliximab (Remicade), and cyclosporine.13 Topical therapies are used as adjuvants to systemic therapy. Systemic glucocorticoids can induce rapid improvement in GPP but have been identified as a potential precipitant.
A recent review comparing the efficacy and safety of biologic agents in the treatment of pediatric GPP concluded that etanercept should be considered before infliximab and adalimumab (Humira) as a first-line biologic agent due its comparatively favorable efficacy and safety profile.14 However, the eruption of lesions of pustular psoriasis has been associated with TNF-α inhibitors.15,16
Chief features of the disease are its tendency to recur and its persistence. The course of GPP is often associated with periods of quiescence and recurrence over the course of years. However, with therapy, flares may be avoided.1
Drs Peters and Ballin are with the United States Navy Medical Corps.
This article originally appeared in Consultant. 2017;57(8):493-497.
References
1. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF. Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol. 2014;53(6):676-684.
2. Borges-Costa J, Silva R, Gonçalves L, Filipe P, Soares de Almeida L, Marques Gomes M. Clinical and laboratory features in acute generalized pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol. 2011;12(4):271-276.
3. Georgala S, Koumantaki E, Rallis E, Papadavid E. Generalized pustular psoriasis developing during withdrawal of short-term cyclosporin therapy. Br J Dermatol. 2000;142(5):1057-1058.
4. Sugiura K, Shoda Y, Akiyama M. Generalized pustular psoriasis triggered by amoxicillin in monozygotic twins with compound heterozygous IL36RN mutations: comment on the article by Navarini et al. J Invest Dermatol. 2014;134(2):578-579.
5. Wu M-C, Lee J-Y. Generalized flare of pustular psoriasis induced by PEGylated interferon-α2b therapy for chronic hepatitis C. Australas J Dermatol. 2012;53(4):e69-e72.
6. Shmidt E, Wetter DA, Ferguson SB, Pittelkow MR. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol. 2012;67(5):e179-e185.
7. Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol. 2006;24(2):101-104.
8. Lowe NJ, Ridgway HB. Generalized pustular psoriasis precipitated by lithium carbonate. Arch Dermatol. 1978;114(12):1788-1789.
9. Katz M, Seidenbaum M, Weinrauch L. Penicillin-induced generalized pustular psoriasis. J Am Acad Dermatol. 1987;17(5 pt 2):918-920.
10. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010;37(12):1220-1229.
11. Kalb RE. Pustular psoriasis: pathogenesis, clinical manifestations, and diagnosis. UpToDate. https://www.uptodate.com/contents/pustular-psoriasis-pathogenesis-clinical-manifestations-and-diagnosis Updated December 30, 2016. Accessed July 19, 2017.
12. Duckworth L, Maheshwari MB, Thomson MA. A diagnostic challenge: acute generalized exanthematous pustulosis or pustular psoriasis due to terbinafine. Clin Exp Dermatol. 2012;37(1):24-27.
13. Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(2):279-288.
14. Collamer AN, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. Semin Arthritis Rheum. 2010;40(3):233-240.
15. Saikaly SK, Mattes M. Biologics and pediatric generalized pustular psoriasis: an emerging therapeutic trend. Cureus. 2016;8(6):e652.
16. Ephrem G, Jour G, Smith BL. Successful treatment of von Zumbusch generalized pustular psoriasis with cyclosporine after eruption post etanercept injection. J Med Liban. 2011;59(3):168-169.
An 8-year-old girl with a 4-year history of chronic intermittent eruption of a pustular rash on her torso presented for evaluation in the dermatology clinic with an ongoing flare. The current rash had persisted despite the application of topical fluocinonide, topical clobetasol, a selenium sulfide wash, and oral cephalexin.
Physical Examination
Laboratory test findings were significant for a neutrophilic leukocytosis (14,200 white blood cells/µL). Histologic review of a punch biopsy specimen demonstrated an epidermal and superficial perivascular neutrophilic infiltrate with overlying serum crust. Results of Grocott methenamine silver and periodic acid–Schiff stains were unremarkable.
The results of further evaluation with a basic metabolic panel, serologic testing for hepatitis B, and purified protein derivative skin testing for tuberculosis were normal or negative. Based on her presentation and laboratory test results, the patient received a diagnosis of pustular psoriasis (Figures 1 and 2).
{{pagebreak}}
Treatment
A regimen of weekly subcutaneous etanercept (Enbrel) injections was initiated, which led to near complete resolution of the plaques over the course of several months without perceivable adverse effects.
Figure 3 shows the patient at 6-month follow-up.
Discussion
Pustular psoriasis is an uncommon variant of psoriasis that can develop independently or in association with preexisting psoriasis. The exact prevalence of generalized pustular psoriasis (GPP) is unknown. It is most often seen in middle-aged adults but can occur in children,1,2 as this patient’s case illustrates.
The development of pustular psoriasis has been linked to upper respiratory tract infection, pregnancy, withdrawal of corticosteroids, hypocalcemia, and the use of various medications, including interferon, lithium, penicillin, cyclosporine, salicylates, and tumor necrosis factor α (TNF-α) inhibitors.1,3-9 It is often observed in patients with a history of psoriasis.1,2
Pustular psoriasis is characterized by an acute, subacute, or chronic eruption of sterile pustules associated with erythema and inflammation. This patient’s case represents the annular variant (also called subacute GPP), characterized by pustules on the periphery of expanding erythematous plaques with central healing, most often localized to the trunk. The acute variant (also called von Zumbusch psoriasis) is characterized by the abrupt onset of numerous pustules on a background of widespread erythema with associated systemic symptoms such as fever, malaise, headache, nausea, arthralgia, and skin tenderness. The exanthematous type, acute generalized exanthematous pustulosis (AGEP) is precipitated by medications or infection and is usually not accompanied by systemic symptoms. The localized variant involves eruption of pustules on the palms, soles, fingertips, and/or nail beds.1,2
Laboratory analysis commonly demonstrates leukocytosis of up to 30,000 cells/µL, absolute lymphocytopenia, an elevated erythrocyte sedimentation rate, hypocalcemia, transaminitis, hypoalbuminemia, and/or an elevated antistreptolysin antibody level. Cultures of the pustules will usually not yield significant growth of pathogenic organisms unless superinfection is present.1 The diagnosis is solidified with skin biopsy findings, which commonly demonstrate classic psoriasiform changes, including parakeratosis and elongation of the rete ridges, along with an epidermal neutrophil infiltrate, upper dermal perivascular lymphocyte infiltrate, and intraspinous aggregates of neutrophils known as spongiform pustules of Kogoj.10
The differential diagnosis mainly includes dermatitis with secondary infection, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), IgA pemphigus, tinea corporis, and AGEP.11 Distinguishing GPP from AGEP can be challenging, because the clinical presentations are nearly identical. However, AGEP is more likely to be associated with antibiotic use.12 Biopsy findings that favor AGEP include a lack of significant psoriasiform changes, the presence of a mixed neutrophil-rich infiltrate, eosinophils and necrotic keratinocytes in the dermis, and lack of tortuous blood vessels.10
Patients with acute GPP may require hospitalization to ensure adequate supportive care. Causative drugs must be identified and discontinued. First-line systemic agents include acitretin, methotrexate, infliximab (Remicade), and cyclosporine.13 Topical therapies are used as adjuvants to systemic therapy. Systemic glucocorticoids can induce rapid improvement in GPP but have been identified as a potential precipitant.
A recent review comparing the efficacy and safety of biologic agents in the treatment of pediatric GPP concluded that etanercept should be considered before infliximab and adalimumab (Humira) as a first-line biologic agent due its comparatively favorable efficacy and safety profile.14 However, the eruption of lesions of pustular psoriasis has been associated with TNF-α inhibitors.15,16
Chief features of the disease are its tendency to recur and its persistence. The course of GPP is often associated with periods of quiescence and recurrence over the course of years. However, with therapy, flares may be avoided.1
Drs Peters and Ballin are with the United States Navy Medical Corps.
This article originally appeared in Consultant. 2017;57(8):493-497.
References
1. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF. Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol. 2014;53(6):676-684.
2. Borges-Costa J, Silva R, Gonçalves L, Filipe P, Soares de Almeida L, Marques Gomes M. Clinical and laboratory features in acute generalized pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol. 2011;12(4):271-276.
3. Georgala S, Koumantaki E, Rallis E, Papadavid E. Generalized pustular psoriasis developing during withdrawal of short-term cyclosporin therapy. Br J Dermatol. 2000;142(5):1057-1058.
4. Sugiura K, Shoda Y, Akiyama M. Generalized pustular psoriasis triggered by amoxicillin in monozygotic twins with compound heterozygous IL36RN mutations: comment on the article by Navarini et al. J Invest Dermatol. 2014;134(2):578-579.
5. Wu M-C, Lee J-Y. Generalized flare of pustular psoriasis induced by PEGylated interferon-α2b therapy for chronic hepatitis C. Australas J Dermatol. 2012;53(4):e69-e72.
6. Shmidt E, Wetter DA, Ferguson SB, Pittelkow MR. Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010. J Am Acad Dermatol. 2012;67(5):e179-e185.
7. Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol. 2006;24(2):101-104.
8. Lowe NJ, Ridgway HB. Generalized pustular psoriasis precipitated by lithium carbonate. Arch Dermatol. 1978;114(12):1788-1789.
9. Katz M, Seidenbaum M, Weinrauch L. Penicillin-induced generalized pustular psoriasis. J Am Acad Dermatol. 1987;17(5 pt 2):918-920.
10. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010;37(12):1220-1229.
11. Kalb RE. Pustular psoriasis: pathogenesis, clinical manifestations, and diagnosis. UpToDate. https://www.uptodate.com/contents/pustular-psoriasis-pathogenesis-clinical-manifestations-and-diagnosis Updated December 30, 2016. Accessed July 19, 2017.
12. Duckworth L, Maheshwari MB, Thomson MA. A diagnostic challenge: acute generalized exanthematous pustulosis or pustular psoriasis due to terbinafine. Clin Exp Dermatol. 2012;37(1):24-27.
13. Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(2):279-288.
14. Collamer AN, Battafarano DF. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. Semin Arthritis Rheum. 2010;40(3):233-240.
15. Saikaly SK, Mattes M. Biologics and pediatric generalized pustular psoriasis: an emerging therapeutic trend. Cureus. 2016;8(6):e652.
16. Ephrem G, Jour G, Smith BL. Successful treatment of von Zumbusch generalized pustular psoriasis with cyclosporine after eruption post etanercept injection. J Med Liban. 2011;59(3):168-169.
