doi: 10.1111/1346-8138.12863
Journal of Dermatology 2015; 42: 674–678
ORIGINAL ARTICLE
Clinical features and course of generalized pustular psoriasis in Korea Hyunju JIN,1 Hyun-Ho CHO,1 Won-Jeong KIM,1 Je-Ho MUN,1 Margaret SONG,1 Hoon-Soo KIM,1 Hyun-Chang KO,1,2 Moon-Bum KIM,1,2 Hyojin KIM,3 Byung-Soo KIM1,2 1
Department of Dermatology, 2Biomedical Research Institute, Pusan National University Hospital, 3Department of Dermatology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea
ABSTRACT 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 45.6 years 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 2 months 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.
Key words:
clinical course, clinical feature, complication, generalized pustular psoriasis, relapse.
INTRODUCTION Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis that is characterized by generalized, tiny, sterile pustules.1 GPP has a variety of clinical features, and can be divided into four subtypes consisting of acute GPP, GPP of pregnancy, juvenile GPP and annular GPP.2 Few publications detail the clinical course of GPP, including a report in which Ryan and Baker.1 studied the clinical course and prognosis of GPP in 155 patients according to the pattern of psoriasis at its onset. Compared with plaque psoriasis, GPP is more frequently associated with extensive exfoliation, generalized symptoms or severe complications. Despite its heterogeneity, it is important to recognize the overall clinical course of GPP for an accurate prognosis of the disease. In this retrospective study, we investigated the clinical features of GPP according to subtype. We also evaluated the clinical course and relapse pattern of skin lesions according to a history of plaque-type psoriasis.
METHODS This study was approved by the institutional review board of Pusan National University Hospital. Medical records and
clinical photos were reviewed and a telephone survey was performed for 33 histopathologically confirmed GPP patients who visited two tertiary hospitals (Pusan National University Hospital and Busan Paik Hospital) between January 2002 and December 2012. Clinical features and clinical course were analyzed according to the subtype of GPP and the presence of the previous plaque psoriasis. According to the classification system proposed by Elder et al.,2 GPP was divided into four subtypes: (i) acute GPP; (ii) GPP of pregnancy; (iii) juvenile GPP; and (iv) annular GPP. Subtypes were categorized according to the mode of onset and the distribution of the lesions. Patients who developed pustular lesions in more than two anatomical subunits were categorized as acute GPP. GPP of pregnancy was diagnosed if GPP had first been developed during pregnancy. Patients with onset age under 18 years were categorized as juvenile GPP. Lastly, patients with annular or gyrate lesions and with localized distribution were classified as annular GPP. Clinical features such as the age of the patient, onset age, the affected body surface area, a family history of psoriasis, a history of plaque psoriasis, involvement of the scalp and nails, associated symptoms, aggravating factors and results of laboratory tests were investigated. For patients with more than 1 year of follow up, the treatment period to achieve clearance
Correspondence: Byung-Soo Kim, M.D., Ph.D., Department of Dermatology, School of Medicine, Pusan National University, 179 Gudeok-ro, Seo-gu, Busan 602-739, Korea. Email: [email protected] Received 24 July 2014; accepted 16 February 2015.
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© 2015 Japanese Dermatological Association Arthralgia Chills Fever Infection Medication Pregnancy Seasons Steroid withdrawal Elevated ESR Hypoalbuminemia Hypocalcemia Leukocytosis
33 (15:18) 45.6 21.5 40.7 22.0 65.6 0 (0.0) 14 (42.4) 10 (30.3) 7 (21.2) 5 (15.2) 10 (30.3) 8 (24.2) 8 (24.2) 5 (15.2) 2 (6.1) 3 (9.1) 2 (6.1) 19/20 (95.0) 15/21 (71.4) 16/21 (76.2) 21/29 (72.4)
Total 21 (9:12) 53.0 22.0 47.6 21.7 81.9 0 (0.0) 11 (52.4) 6 (28.6) 7 (33.3) 5 (23.8) 6 (28.6) 5 (23.8) 5 (23.8) 5 (23.8) 0 (0.0) 1 (4.8) 2 (9.5) 13/14 (92.9) 12/14 (85.7) 13/14 (92.9) 15/19 (78.9)
2 (0:2) 33.0 1.4 25.5 2.1 54.0 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100.0) 2 (100.0) 0 (0.0) 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 2/2 (100.0) 2/2 (100.0) 2/2 (100.0) 2/2 (100.0)
GPP of pregnancy (6.1%) 3 (2:1) 7.3 2.5 6.3 3.5 66.7 0 (0.0) 1 (33.3) 2 (66.6) 0 (0.0) 0 (0.0) 2 (66.6) 1 (33.3) 3 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2/2 (100.0) 1/2 (50.0) 1/2 (50.0) 2/2 (100.0)
Juvenile GPP (9.1%) 7 (4:3) 42.3 13.9 39.0 13.0 23.2 0 (0.0) 2 (28.6) 2 (28.6) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (28.6) 0 (0.0) 2/2 (100.0) 0/3 (0.0) 0/3 (0.0) 2/6 (33.3)
Annular GPP (21.2%)
14 (9:5) 44.6 24.9 39.3 24.8 71.8 0 (0.0) – – – 1 (7.1) 4 (28.6) 3 (21.4) 4 (28.6) 3 (21.4) 0 (0.0) 2 (14.3) 2 (14.3) 8/8 (100.0) 6/11 (54.5) 7/11 (63.6) 10/13 (76.9)
With plaque psoriasis (42.4%)
19 (6:13) 46.4 19.2 41.7 20.4 61.0 0 (0.0) – – – 4 (21.1) 6 (31.6) 5 (26.3) 4 (21.1) 2 (10.5) 2 (10.5) 1 (5.3) 0 (0.0) 11/12 (91.7) 9/10 (90.0) 9/10 (90.0) 11/16 (68.8)
Without plaque psoriasis (57.6%)
– 0.82 0.77 0.35 – – – – 0.36 1.00 1.00 0.70 0.63 0.50 0.56 0.17 1.00 0.15 0.31 0.70
P*
Categorized according to previous history of plaque psoriasis
BSA, body surface area; ESR, erythrocyte sedimentation rate; FHx, family history of plaque psoriasis; GPP, generalized pustular psoriasis; PHx, past history of plaque psoriasis; SD, standard deviation. *P-values represent a comparison between GPP with PHx vs GPP without PHx. P < 0.05 is considered statistically significant.
Laboratory findings, n/n tested (%)
Aggravating factors, n (%)
Total number of patients (M:F) Age (mean SD, years) Age of onset (mean SD, years) Mean BSA (%) FHx, n (%) PHx, n (%) Involvement of scalp, n (%) Involvement of nails, n (%) Associated symptoms, n (%)
Acute GPP (63.6%)
Categorized according to four subtypes
Table 1. Clinical features according to subtypes of GPP and presence of previous plaque psoriasis
Clinical features and course of GPP in Korea
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GPP, generalized pustular psoriasis; PHx, past history of plaque psoriasis; SD, standard deviation. *P-values represent a comparison between GPP with PHx vs GPP without PHx. P < 0.05 is considered statistically significant.
0.40 0.40 1.00 1.00 0.35 0.35 (60.0) (40.0) (6.7) (6.7) (33.3) (66.7) 9 6 1 1 5 10 (80.0) (20.0) (0.0) (0.0) (10.0) (90.0) 8 2 0 0 1 9 (40.0) (60.0) (0.0) (0.0) (0.0) (100.0) 2 3 0 0 0 5 (100.0) (0.0) (0.0) (0.0) (0.0) (100.0) 3 0 0 0 0 3 (50.0) (50.0) (50.0) (50.0) (0.0) (100.0) 1 1 1 1 0 2 (73.3) (26.7) (0.0) (0.0) (40.0) (60.0)
– 0.89 0.95 – 15 (4:11) 43.0 17.1 38.1 18.0 51.2 29.6 10 (6:4) 44.4 28.4 38.7 28.8 65.2 44.3 5 (3:2) 42.0 14.4 40.2 15.5 43.5 32.8 3 (2:1) 7.3 2.5 6.3 3.5 76.7 24.0 2 (0:2) 33.0 1.4 25.5 2.1 42.5 41.7 15 (5:10) 51.0 22.1 45.8 22.0 60.3 39.2
11 4 0 0 6 9 (68.0) (32.0) (4.0) (4.0) (24.0) (76.0) 17 8 1 1 6 19
Total
Total number of patients (M:F) Age (mean SD, years) Age of onset (mean SD, years) Follow-up periods, months (mean SD) Treatment period to achieve ≤2 months clearance of skin lesion, n (%) >2 months Severe complications, n (%) Abortion Death Outcome, n (%) No relapse Persistence/relapse
25 (10:15) 43.6 21.7 38.3 22.4 56.8 36.0
Without plaque psoriasis (60.0%) With plaque psoriasis (40.0%) GPP of pregnancy (8.0%) Acute GPP (60.0%)
Categorized according to four subtypes
A total of 33 patients (15 men and 18 women) were included in this study. Clinical features of the 33 patients are detailed in Table 1. The mean age (45.6 years) and mean affected body surface area (65.6%) of the acute GPP patients was the highest amongst the subtypes. No patient admitted to being part of a family of psoriasis patients. A history of plaque psoriasis (42.4%) was most frequently observed in patients with acute GPP. Scalp involvement (28.6%) was the most frequent in patients with acute GPP and nail involvement (33.3%) was only detected in patients with acute GPP. All patients with GPP of pregnancy complained of chills and fever, while no patient with annular GPP experienced such symptoms. Details of the aggravating factors in 16 patients are listed as being infection in eight and medication in five, along with other causes. Infection included six cases of upper respiratory infection, one case of pneumonia and one case of cellulitis. Medication included two cases of antibiotics, one case of anticonvulsant, one case of contrast media and one case of oriental medicine. Elevated erythrocyte sedimentation rate was observed in most of the patients, regardless of subtypes. Hypoalbuminemia, hypocalcemia or leukocytosis were least frequently observed in patients with annular GPP. There was no significant difference between two groups concerning the previous history of plaque psoriasis (P > 0.05). Among the 33 patients, 25 (10 men and 15 women) were available for follow up for at least 1 year. Table 2 displays the clinical courses of GPP according to the subtype in patients with a more than 1-year follow-up period. The rate for achieving skin lesion clearance with a treatment period of 2 months or less was the highest in juvenile GPP (100.0%) and the lowest in annular GPP (40.0%). The proportion of patients who showed persistence/relapse was higher in the group with the previous plaque psoriasis than the group without the previous plaque psoriasis. The rate for achieving skin lesion clearance with a treatment period of 2 months or less were higher in patients without previous plaque psoriasis. However, the difference between two groups did not show statistical significance (P > 0.05). Severe complications were observed only in the
Table 2. Clinical course according to subtypes of GPP and presence of previous plaque psoriasis
RESULTS
Juvenile GPP (12.0%)
Annular GPP (20.0%)
Categorized according to previous history of plaque psoriasis
of skin lesions, severe complications, clinical course and the relapse pattern of any skin lesions were included for investigation. To investigate the clinical course, we defined no relapse as cases in which skin lesions did not reappear after 1 year or more without any treatment, and persistence/relapse as cases in which GPP was persistent or relapsed within 1 year. The pattern of relapse was divided into three types: (i) plaque; (ii) pustules; or (iii) plaque and pustules. Further, the patients were divided into two groups: one group with a previous history of plaque psoriasis and another group without a previous history of plaque psoriasis. Clinical features and course were analyzed according to these two groups. The groups were compared using Student’s t-test of Fisher’s exact test. The level of statistical significance was set at P < 0.05. The statistical package included in SPSS version 21.0 software was used (SPSS, Chicago, IL, USA).
P*
H. Jin et al.
© 2015 Japanese Dermatological Association
Clinical features and course of GPP in Korea
Table 3. Skin lesion during persistence/relapse period according to subtypes of GPP
Total number of patients (M:F) PHx of plaque psoriasis, n (%) Age (mean SD, years) Age of onset (mean SD, years) Type of skin lesion, n (%) Only plaque Only pustules Plaque and pustules
Total
Acute GPP (47.4%)
GPP of pregnancy (10.5%)
Juvenile GPP (15.8%)
Annular GPP (26.3%)
19 (9:10) 9 (47.3) 42.0 25.6 36.8 24.2 6 (31.6) 8 (42.1) 5 (26.3)
9 (4:5) 7 (77.8) 52.7 23.4 47.7 5.9 3 (33.3) 5 (55.6) 1 (11.1)
2 (0:2) 0 (0.0) 33.0 1.4 25.5 2.1 0 (0.0) 0 (0.0) 2 (100.0)
3 (2:1) 1 (33.3) 13.6 5.6 6.3 3.5 3 (100.0) 0 (0.0) 0 (0.0)
5 (3:2) 1 (20.0) 42.0 17.6 40.2 15.5 0 (0.0) 3 (60.0) 2 (40.0)
GPP, generalized pustular psoriasis; PHx, past history of plaque psoriasis; SD, standard deviation.
GPP of pregnancy group, which included a case of abortion and a case of death. During the clinical course, no relapse was observed in six patients (40.0%) with acute GPP but in no patients with other subtypes. Persistence/relapse were detected in nine patients (60.0%) with acute GPP; seven (77.8%) of them had a history of plaque psoriasis and two (22.2%) of them did not. Nineteen patients were assessed for persistence/relapse and Table 3 summarizes such details. In acute GPP, patients showed diverse types of skin lesion upon relapse. Patients with GPP of pregnancy showed plaque and pustules upon relapse, while juvenile GPP patients showed only plaque lesions upon relapse. In patients with acute GPP, seven patients (77.8%) with a history of plaque psoriasis presented various types of skin lesions upon relapse. However, two patients (22.2%) without a history of plaque psoriasis experienced a pustular type of relapse. Two patients with GPP of pregnancy and no history of plaque psoriasis developed plaque and pustule skin lesions during pregnancy and menstruation. Three patients with juvenile GPP exhibited the plaque form of relapse regardless of history of plaque psoriasis. Among the five patients with annular GPP, one patient (20.0%) with a history of plaque psoriasis exhibited plaque and pustules and four patients (80.0%) with no history of plaque psoriasis exhibited pustules or plaque and pustules.
DISCUSSION The present study identifies some GPP clinical features already known and several novel findings as well. In our study, the mean age of patients was 45.6 years, which is similar to the 40–60-year range reported by Baker3 but a little higher than the 35.8 years that Youn et al.4 suggested as the mean age of Korean GPP patients, as well as the 41.0 years that Tay et al.5 suggested as the mean age of Singaporean GPP patients. In previous studies, GPP more frequently occurred in women, and Youn et al.4 reported a male : female ratio of 1:2. In this study, the male : female ratio was 1:1.2 in which our proportion of men was considerably higher than the previous studies. A previous study reported that 10.7% of GPP patients had a history of plaque psoriasis.5 However, the percentage of patients with a history of plaque psoriasis was 42.4% in this study population (Table 1). In cases of acute GPP, Youn et al.4
© 2015 Japanese Dermatological Association
reported that arthralgia, chills and fever were associated in 25.0%, 37.5% and 62.5% of patients, respectively. In our study, while rates of arthralgia were similar (23.8%), chills (28.6%) and fever (23.8%) were significantly lower. This may be due to the incompleteness of medical records regarding subjective symptoms. Our study identified infections, medications, climate/season, pregnancy and steroid tapering as aggravating factors of GPP (Table 1), which is consistent with previous studies that reported infection, pregnancy, drug use, climate/season or menstruation as aggravating factors of GPP.5,6 With regard to the clinical course of GPP, those with acute GPP tend to experience several episodes of symptom aggravation and significant complications and mortality.6 However, in this study, six (40.0%) of 15 patients did not undergo relapse during 1 year of follow up, no patient had severe complications such as death and the treatment period was less than 2 months in 11 (73.3%) patients. Improved conservative treatment for the acute period leads to an improved prognosis. In the GPP of pregnancy group, the patients are known to develop GPP during the third trimester without any history of plaque psoriasis. Although GPP may recur during subsequent pregnancies, the skin lesions resolve spontaneously after delivery, so the prognosis is generally good.5,7 However, patients with GPP of pregnancy have also reported relapse during menstruation after delivery.8 In our study, two patients with GPP of pregnancy developed skin lesions during pregnancy that resolved spontaneously after delivery, but recurred during menstruation. One patient underwent abortion during her second pregnancy and the other patient died during the course of aggravation. Among the subtypes of GPP, GPP of pregnancy showed the worst prognosis. Unlike those for other subtypes of GPP, aggravating factors in GPP of pregnancy are related to hormonal effects such as pregnancy or menstruation. In juvenile GPP, the clinical course showed chronicity and recurrence, but no severe complications were observed. This agrees with previous studies reporting that juvenile patients have better prognoses than adult patients.9– 12 It has been reported that those with annular GPP displayed a subacute course and chronicity of symptoms that are well controlled with conservative treatment.6 In our study, those with annular GPP showed a chronic clinical course, but no severe complications.
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Among the 15 patients with acute GPP, one (16.7%) out of six patients with no relapse had a history of plaque psoriasis, whereas seven (77.8%) of nine patients with a history of plaque psoriasis had persistence/relapse. It seems that patients with a history of plaque psoriasis had a greater risk of recurrence than patients with no history of plaque psoriasis. In the other subtypes, the number of patients in each group was too small to analyze the relationship between relapse and history of plaque psoriasis. In those with juvenile GPP, regardless of the history of plaque psoriasis, skin lesions recurred only in the plaque form. In those with annular GPP, all patients showed relapse with pustules or plaques and pustules. A treatment guideline for GPP has not been established and there is little evidence-based management of GPP. Acitretin, cyclosporin, methotrexate and infliximab are considered to be the first-line therapies.13 For children and pregnant women, individual modification of treatment regimen is required.13 In the present study, each patient had been treated with various topical and systemic agents for diverse durations. So, the data were not suitable to assess the efficacy of each treatment modality. This is an important study that investigated the clinical course and prognosis of GPP. We confirmed the aggravating factors and relapsing pattern of GPP. Unlike previous reports, the ratio of female to male patients was similar. In this study, patients with acute GPP showed a better prognosis than previously reported, and those with GPP of pregnancy showed a poor prognosis. Patients with previous plaque psoriasis have a tendency to show prolonged disease course. However, the difference of outcome between two groups did not show statistical significance. These results will help us better understand the clinical course of GPP, which is not fully appreciated, and aid in treating GPP.
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CONFLICT OF INTEREST:
None.
REFERENCES 1 Ryan TJ, Baker H. The prognosis of generalized pustular psoriasis. Br J Dermatol 1971; 85: 407–411. 2 Elder DE. Histopathology of the Skin, 10th edn. Philadelphia: Lippincott Williams & Wilkins, 2008. 3 Baker H, Ryan TJ. Generalized pustular psoriasis. A clinical and epidemiological study of 104 cases. Br J Dermatol 1968; 80: 771–793. 4 Youn JI, Oh JG. The clinical study of generalized pustular psoriasis. Kor J Dermatol 1996; 34: 233–239. 5 Tay YK, Tham SN. The profile and outcome of pustular psoriasis in Singapore: a report of 28 cases. Int J Dermatol 1997; 36: 266–271. 6 Zelickson BD, Muller SA. Generalized pustular psoriasis. A review of 63 cases. Arch Dermatol 1991; 127: 1339–1345. 7 Breier-Maly J, Ortel B, Breier F et al. Generalized pustular psoriasis of pregnancy (impetigo herpetiformis). Dermatology 1999; 198: 61– 64. 8 Chaidemenos G, Lefaki I, Tsakiri A et al. Impetigo herpetiformis: menstrual exacerbations for 7 years postpartum. J Eur Acad Dermatol Venereol 2005; 19: 466–469. 9 Xiao T, Li B, He CD et al. Juvenile generalized pustular psoriasis. J Dermatol 2007; 34: 573–576. 10 de Oliveira ST, Maragno L, Arnone M et al. Generalized pustular psoriasis in childhood. Pediatr Dermatol 2010; 27: 349–354. 11 Stefanaki C, Lagogianni E, Kontochristopoulos G et al. Psoriasis in children: a retrospective analysis. J Eur Acad Dermatol Venereol 2011; 25: 417–421. 12 Ryan TJ, Baker H. Systemic corticosteroids and folic acid antagonists in the treatment of generalized pustular psoriasis. Evaluation and prognosis based on the study of 104 cases. Br J Dermatol 1969; 81: 134–145. 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: 279–288.
© 2015 Japanese Dermatological Association
Journal of Dermatology 2015; 42: 674–678
ORIGINAL ARTICLE
Clinical features and course of generalized pustular psoriasis in Korea Hyunju JIN,1 Hyun-Ho CHO,1 Won-Jeong KIM,1 Je-Ho MUN,1 Margaret SONG,1 Hoon-Soo KIM,1 Hyun-Chang KO,1,2 Moon-Bum KIM,1,2 Hyojin KIM,3 Byung-Soo KIM1,2 1
Department of Dermatology, 2Biomedical Research Institute, Pusan National University Hospital, 3Department of Dermatology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea
ABSTRACT 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 45.6 years 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 2 months 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.
Key words:
clinical course, clinical feature, complication, generalized pustular psoriasis, relapse.
INTRODUCTION Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis that is characterized by generalized, tiny, sterile pustules.1 GPP has a variety of clinical features, and can be divided into four subtypes consisting of acute GPP, GPP of pregnancy, juvenile GPP and annular GPP.2 Few publications detail the clinical course of GPP, including a report in which Ryan and Baker.1 studied the clinical course and prognosis of GPP in 155 patients according to the pattern of psoriasis at its onset. Compared with plaque psoriasis, GPP is more frequently associated with extensive exfoliation, generalized symptoms or severe complications. Despite its heterogeneity, it is important to recognize the overall clinical course of GPP for an accurate prognosis of the disease. In this retrospective study, we investigated the clinical features of GPP according to subtype. We also evaluated the clinical course and relapse pattern of skin lesions according to a history of plaque-type psoriasis.
METHODS This study was approved by the institutional review board of Pusan National University Hospital. Medical records and
clinical photos were reviewed and a telephone survey was performed for 33 histopathologically confirmed GPP patients who visited two tertiary hospitals (Pusan National University Hospital and Busan Paik Hospital) between January 2002 and December 2012. Clinical features and clinical course were analyzed according to the subtype of GPP and the presence of the previous plaque psoriasis. According to the classification system proposed by Elder et al.,2 GPP was divided into four subtypes: (i) acute GPP; (ii) GPP of pregnancy; (iii) juvenile GPP; and (iv) annular GPP. Subtypes were categorized according to the mode of onset and the distribution of the lesions. Patients who developed pustular lesions in more than two anatomical subunits were categorized as acute GPP. GPP of pregnancy was diagnosed if GPP had first been developed during pregnancy. Patients with onset age under 18 years were categorized as juvenile GPP. Lastly, patients with annular or gyrate lesions and with localized distribution were classified as annular GPP. Clinical features such as the age of the patient, onset age, the affected body surface area, a family history of psoriasis, a history of plaque psoriasis, involvement of the scalp and nails, associated symptoms, aggravating factors and results of laboratory tests were investigated. For patients with more than 1 year of follow up, the treatment period to achieve clearance
Correspondence: Byung-Soo Kim, M.D., Ph.D., Department of Dermatology, School of Medicine, Pusan National University, 179 Gudeok-ro, Seo-gu, Busan 602-739, Korea. Email: [email protected] Received 24 July 2014; accepted 16 February 2015.
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© 2015 Japanese Dermatological Association
© 2015 Japanese Dermatological Association Arthralgia Chills Fever Infection Medication Pregnancy Seasons Steroid withdrawal Elevated ESR Hypoalbuminemia Hypocalcemia Leukocytosis
33 (15:18) 45.6 21.5 40.7 22.0 65.6 0 (0.0) 14 (42.4) 10 (30.3) 7 (21.2) 5 (15.2) 10 (30.3) 8 (24.2) 8 (24.2) 5 (15.2) 2 (6.1) 3 (9.1) 2 (6.1) 19/20 (95.0) 15/21 (71.4) 16/21 (76.2) 21/29 (72.4)
Total 21 (9:12) 53.0 22.0 47.6 21.7 81.9 0 (0.0) 11 (52.4) 6 (28.6) 7 (33.3) 5 (23.8) 6 (28.6) 5 (23.8) 5 (23.8) 5 (23.8) 0 (0.0) 1 (4.8) 2 (9.5) 13/14 (92.9) 12/14 (85.7) 13/14 (92.9) 15/19 (78.9)
2 (0:2) 33.0 1.4 25.5 2.1 54.0 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100.0) 2 (100.0) 0 (0.0) 0 (0.0) 2 (100.0) 0 (0.0) 0 (0.0) 2/2 (100.0) 2/2 (100.0) 2/2 (100.0) 2/2 (100.0)
GPP of pregnancy (6.1%) 3 (2:1) 7.3 2.5 6.3 3.5 66.7 0 (0.0) 1 (33.3) 2 (66.6) 0 (0.0) 0 (0.0) 2 (66.6) 1 (33.3) 3 (100.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2/2 (100.0) 1/2 (50.0) 1/2 (50.0) 2/2 (100.0)
Juvenile GPP (9.1%) 7 (4:3) 42.3 13.9 39.0 13.0 23.2 0 (0.0) 2 (28.6) 2 (28.6) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (28.6) 0 (0.0) 2/2 (100.0) 0/3 (0.0) 0/3 (0.0) 2/6 (33.3)
Annular GPP (21.2%)
14 (9:5) 44.6 24.9 39.3 24.8 71.8 0 (0.0) – – – 1 (7.1) 4 (28.6) 3 (21.4) 4 (28.6) 3 (21.4) 0 (0.0) 2 (14.3) 2 (14.3) 8/8 (100.0) 6/11 (54.5) 7/11 (63.6) 10/13 (76.9)
With plaque psoriasis (42.4%)
19 (6:13) 46.4 19.2 41.7 20.4 61.0 0 (0.0) – – – 4 (21.1) 6 (31.6) 5 (26.3) 4 (21.1) 2 (10.5) 2 (10.5) 1 (5.3) 0 (0.0) 11/12 (91.7) 9/10 (90.0) 9/10 (90.0) 11/16 (68.8)
Without plaque psoriasis (57.6%)
– 0.82 0.77 0.35 – – – – 0.36 1.00 1.00 0.70 0.63 0.50 0.56 0.17 1.00 0.15 0.31 0.70
P*
Categorized according to previous history of plaque psoriasis
BSA, body surface area; ESR, erythrocyte sedimentation rate; FHx, family history of plaque psoriasis; GPP, generalized pustular psoriasis; PHx, past history of plaque psoriasis; SD, standard deviation. *P-values represent a comparison between GPP with PHx vs GPP without PHx. P < 0.05 is considered statistically significant.
Laboratory findings, n/n tested (%)
Aggravating factors, n (%)
Total number of patients (M:F) Age (mean SD, years) Age of onset (mean SD, years) Mean BSA (%) FHx, n (%) PHx, n (%) Involvement of scalp, n (%) Involvement of nails, n (%) Associated symptoms, n (%)
Acute GPP (63.6%)
Categorized according to four subtypes
Table 1. Clinical features according to subtypes of GPP and presence of previous plaque psoriasis
Clinical features and course of GPP in Korea
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GPP, generalized pustular psoriasis; PHx, past history of plaque psoriasis; SD, standard deviation. *P-values represent a comparison between GPP with PHx vs GPP without PHx. P < 0.05 is considered statistically significant.
0.40 0.40 1.00 1.00 0.35 0.35 (60.0) (40.0) (6.7) (6.7) (33.3) (66.7) 9 6 1 1 5 10 (80.0) (20.0) (0.0) (0.0) (10.0) (90.0) 8 2 0 0 1 9 (40.0) (60.0) (0.0) (0.0) (0.0) (100.0) 2 3 0 0 0 5 (100.0) (0.0) (0.0) (0.0) (0.0) (100.0) 3 0 0 0 0 3 (50.0) (50.0) (50.0) (50.0) (0.0) (100.0) 1 1 1 1 0 2 (73.3) (26.7) (0.0) (0.0) (40.0) (60.0)
– 0.89 0.95 – 15 (4:11) 43.0 17.1 38.1 18.0 51.2 29.6 10 (6:4) 44.4 28.4 38.7 28.8 65.2 44.3 5 (3:2) 42.0 14.4 40.2 15.5 43.5 32.8 3 (2:1) 7.3 2.5 6.3 3.5 76.7 24.0 2 (0:2) 33.0 1.4 25.5 2.1 42.5 41.7 15 (5:10) 51.0 22.1 45.8 22.0 60.3 39.2
11 4 0 0 6 9 (68.0) (32.0) (4.0) (4.0) (24.0) (76.0) 17 8 1 1 6 19
Total
Total number of patients (M:F) Age (mean SD, years) Age of onset (mean SD, years) Follow-up periods, months (mean SD) Treatment period to achieve ≤2 months clearance of skin lesion, n (%) >2 months Severe complications, n (%) Abortion Death Outcome, n (%) No relapse Persistence/relapse
25 (10:15) 43.6 21.7 38.3 22.4 56.8 36.0
Without plaque psoriasis (60.0%) With plaque psoriasis (40.0%) GPP of pregnancy (8.0%) Acute GPP (60.0%)
Categorized according to four subtypes
A total of 33 patients (15 men and 18 women) were included in this study. Clinical features of the 33 patients are detailed in Table 1. The mean age (45.6 years) and mean affected body surface area (65.6%) of the acute GPP patients was the highest amongst the subtypes. No patient admitted to being part of a family of psoriasis patients. A history of plaque psoriasis (42.4%) was most frequently observed in patients with acute GPP. Scalp involvement (28.6%) was the most frequent in patients with acute GPP and nail involvement (33.3%) was only detected in patients with acute GPP. All patients with GPP of pregnancy complained of chills and fever, while no patient with annular GPP experienced such symptoms. Details of the aggravating factors in 16 patients are listed as being infection in eight and medication in five, along with other causes. Infection included six cases of upper respiratory infection, one case of pneumonia and one case of cellulitis. Medication included two cases of antibiotics, one case of anticonvulsant, one case of contrast media and one case of oriental medicine. Elevated erythrocyte sedimentation rate was observed in most of the patients, regardless of subtypes. Hypoalbuminemia, hypocalcemia or leukocytosis were least frequently observed in patients with annular GPP. There was no significant difference between two groups concerning the previous history of plaque psoriasis (P > 0.05). Among the 33 patients, 25 (10 men and 15 women) were available for follow up for at least 1 year. Table 2 displays the clinical courses of GPP according to the subtype in patients with a more than 1-year follow-up period. The rate for achieving skin lesion clearance with a treatment period of 2 months or less was the highest in juvenile GPP (100.0%) and the lowest in annular GPP (40.0%). The proportion of patients who showed persistence/relapse was higher in the group with the previous plaque psoriasis than the group without the previous plaque psoriasis. The rate for achieving skin lesion clearance with a treatment period of 2 months or less were higher in patients without previous plaque psoriasis. However, the difference between two groups did not show statistical significance (P > 0.05). Severe complications were observed only in the
Table 2. Clinical course according to subtypes of GPP and presence of previous plaque psoriasis
RESULTS
Juvenile GPP (12.0%)
Annular GPP (20.0%)
Categorized according to previous history of plaque psoriasis
of skin lesions, severe complications, clinical course and the relapse pattern of any skin lesions were included for investigation. To investigate the clinical course, we defined no relapse as cases in which skin lesions did not reappear after 1 year or more without any treatment, and persistence/relapse as cases in which GPP was persistent or relapsed within 1 year. The pattern of relapse was divided into three types: (i) plaque; (ii) pustules; or (iii) plaque and pustules. Further, the patients were divided into two groups: one group with a previous history of plaque psoriasis and another group without a previous history of plaque psoriasis. Clinical features and course were analyzed according to these two groups. The groups were compared using Student’s t-test of Fisher’s exact test. The level of statistical significance was set at P < 0.05. The statistical package included in SPSS version 21.0 software was used (SPSS, Chicago, IL, USA).
P*
H. Jin et al.
© 2015 Japanese Dermatological Association
Clinical features and course of GPP in Korea
Table 3. Skin lesion during persistence/relapse period according to subtypes of GPP
Total number of patients (M:F) PHx of plaque psoriasis, n (%) Age (mean SD, years) Age of onset (mean SD, years) Type of skin lesion, n (%) Only plaque Only pustules Plaque and pustules
Total
Acute GPP (47.4%)
GPP of pregnancy (10.5%)
Juvenile GPP (15.8%)
Annular GPP (26.3%)
19 (9:10) 9 (47.3) 42.0 25.6 36.8 24.2 6 (31.6) 8 (42.1) 5 (26.3)
9 (4:5) 7 (77.8) 52.7 23.4 47.7 5.9 3 (33.3) 5 (55.6) 1 (11.1)
2 (0:2) 0 (0.0) 33.0 1.4 25.5 2.1 0 (0.0) 0 (0.0) 2 (100.0)
3 (2:1) 1 (33.3) 13.6 5.6 6.3 3.5 3 (100.0) 0 (0.0) 0 (0.0)
5 (3:2) 1 (20.0) 42.0 17.6 40.2 15.5 0 (0.0) 3 (60.0) 2 (40.0)
GPP, generalized pustular psoriasis; PHx, past history of plaque psoriasis; SD, standard deviation.
GPP of pregnancy group, which included a case of abortion and a case of death. During the clinical course, no relapse was observed in six patients (40.0%) with acute GPP but in no patients with other subtypes. Persistence/relapse were detected in nine patients (60.0%) with acute GPP; seven (77.8%) of them had a history of plaque psoriasis and two (22.2%) of them did not. Nineteen patients were assessed for persistence/relapse and Table 3 summarizes such details. In acute GPP, patients showed diverse types of skin lesion upon relapse. Patients with GPP of pregnancy showed plaque and pustules upon relapse, while juvenile GPP patients showed only plaque lesions upon relapse. In patients with acute GPP, seven patients (77.8%) with a history of plaque psoriasis presented various types of skin lesions upon relapse. However, two patients (22.2%) without a history of plaque psoriasis experienced a pustular type of relapse. Two patients with GPP of pregnancy and no history of plaque psoriasis developed plaque and pustule skin lesions during pregnancy and menstruation. Three patients with juvenile GPP exhibited the plaque form of relapse regardless of history of plaque psoriasis. Among the five patients with annular GPP, one patient (20.0%) with a history of plaque psoriasis exhibited plaque and pustules and four patients (80.0%) with no history of plaque psoriasis exhibited pustules or plaque and pustules.
DISCUSSION The present study identifies some GPP clinical features already known and several novel findings as well. In our study, the mean age of patients was 45.6 years, which is similar to the 40–60-year range reported by Baker3 but a little higher than the 35.8 years that Youn et al.4 suggested as the mean age of Korean GPP patients, as well as the 41.0 years that Tay et al.5 suggested as the mean age of Singaporean GPP patients. In previous studies, GPP more frequently occurred in women, and Youn et al.4 reported a male : female ratio of 1:2. In this study, the male : female ratio was 1:1.2 in which our proportion of men was considerably higher than the previous studies. A previous study reported that 10.7% of GPP patients had a history of plaque psoriasis.5 However, the percentage of patients with a history of plaque psoriasis was 42.4% in this study population (Table 1). In cases of acute GPP, Youn et al.4
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reported that arthralgia, chills and fever were associated in 25.0%, 37.5% and 62.5% of patients, respectively. In our study, while rates of arthralgia were similar (23.8%), chills (28.6%) and fever (23.8%) were significantly lower. This may be due to the incompleteness of medical records regarding subjective symptoms. Our study identified infections, medications, climate/season, pregnancy and steroid tapering as aggravating factors of GPP (Table 1), which is consistent with previous studies that reported infection, pregnancy, drug use, climate/season or menstruation as aggravating factors of GPP.5,6 With regard to the clinical course of GPP, those with acute GPP tend to experience several episodes of symptom aggravation and significant complications and mortality.6 However, in this study, six (40.0%) of 15 patients did not undergo relapse during 1 year of follow up, no patient had severe complications such as death and the treatment period was less than 2 months in 11 (73.3%) patients. Improved conservative treatment for the acute period leads to an improved prognosis. In the GPP of pregnancy group, the patients are known to develop GPP during the third trimester without any history of plaque psoriasis. Although GPP may recur during subsequent pregnancies, the skin lesions resolve spontaneously after delivery, so the prognosis is generally good.5,7 However, patients with GPP of pregnancy have also reported relapse during menstruation after delivery.8 In our study, two patients with GPP of pregnancy developed skin lesions during pregnancy that resolved spontaneously after delivery, but recurred during menstruation. One patient underwent abortion during her second pregnancy and the other patient died during the course of aggravation. Among the subtypes of GPP, GPP of pregnancy showed the worst prognosis. Unlike those for other subtypes of GPP, aggravating factors in GPP of pregnancy are related to hormonal effects such as pregnancy or menstruation. In juvenile GPP, the clinical course showed chronicity and recurrence, but no severe complications were observed. This agrees with previous studies reporting that juvenile patients have better prognoses than adult patients.9– 12 It has been reported that those with annular GPP displayed a subacute course and chronicity of symptoms that are well controlled with conservative treatment.6 In our study, those with annular GPP showed a chronic clinical course, but no severe complications.
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Among the 15 patients with acute GPP, one (16.7%) out of six patients with no relapse had a history of plaque psoriasis, whereas seven (77.8%) of nine patients with a history of plaque psoriasis had persistence/relapse. It seems that patients with a history of plaque psoriasis had a greater risk of recurrence than patients with no history of plaque psoriasis. In the other subtypes, the number of patients in each group was too small to analyze the relationship between relapse and history of plaque psoriasis. In those with juvenile GPP, regardless of the history of plaque psoriasis, skin lesions recurred only in the plaque form. In those with annular GPP, all patients showed relapse with pustules or plaques and pustules. A treatment guideline for GPP has not been established and there is little evidence-based management of GPP. Acitretin, cyclosporin, methotrexate and infliximab are considered to be the first-line therapies.13 For children and pregnant women, individual modification of treatment regimen is required.13 In the present study, each patient had been treated with various topical and systemic agents for diverse durations. So, the data were not suitable to assess the efficacy of each treatment modality. This is an important study that investigated the clinical course and prognosis of GPP. We confirmed the aggravating factors and relapsing pattern of GPP. Unlike previous reports, the ratio of female to male patients was similar. In this study, patients with acute GPP showed a better prognosis than previously reported, and those with GPP of pregnancy showed a poor prognosis. Patients with previous plaque psoriasis have a tendency to show prolonged disease course. However, the difference of outcome between two groups did not show statistical significance. These results will help us better understand the clinical course of GPP, which is not fully appreciated, and aid in treating GPP.
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CONFLICT OF INTEREST:
None.
REFERENCES 1 Ryan TJ, Baker H. The prognosis of generalized pustular psoriasis. Br J Dermatol 1971; 85: 407–411. 2 Elder DE. Histopathology of the Skin, 10th edn. Philadelphia: Lippincott Williams & Wilkins, 2008. 3 Baker H, Ryan TJ. Generalized pustular psoriasis. A clinical and epidemiological study of 104 cases. Br J Dermatol 1968; 80: 771–793. 4 Youn JI, Oh JG. The clinical study of generalized pustular psoriasis. Kor J Dermatol 1996; 34: 233–239. 5 Tay YK, Tham SN. The profile and outcome of pustular psoriasis in Singapore: a report of 28 cases. Int J Dermatol 1997; 36: 266–271. 6 Zelickson BD, Muller SA. Generalized pustular psoriasis. A review of 63 cases. Arch Dermatol 1991; 127: 1339–1345. 7 Breier-Maly J, Ortel B, Breier F et al. Generalized pustular psoriasis of pregnancy (impetigo herpetiformis). Dermatology 1999; 198: 61– 64. 8 Chaidemenos G, Lefaki I, Tsakiri A et al. Impetigo herpetiformis: menstrual exacerbations for 7 years postpartum. J Eur Acad Dermatol Venereol 2005; 19: 466–469. 9 Xiao T, Li B, He CD et al. Juvenile generalized pustular psoriasis. J Dermatol 2007; 34: 573–576. 10 de Oliveira ST, Maragno L, Arnone M et al. Generalized pustular psoriasis in childhood. Pediatr Dermatol 2010; 27: 349–354. 11 Stefanaki C, Lagogianni E, Kontochristopoulos G et al. Psoriasis in children: a retrospective analysis. J Eur Acad Dermatol Venereol 2011; 25: 417–421. 12 Ryan TJ, Baker H. Systemic corticosteroids and folic acid antagonists in the treatment of generalized pustular psoriasis. Evaluation and prognosis based on the study of 104 cases. Br J Dermatol 1969; 81: 134–145. 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: 279–288.
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