Generalized pustular psoriasis in childhood Report of thirteen cases Brian D. Zelickson, MD, and Sigfrid A. Muller, MD Rochester, Minnesota Generalized pustular psoriasis is rare in children. Less than 100 cases have been reported. We describe 13 children with this type of psoriasis. Seven had acute onset of widespread sterile pustules coalescing into lakes of pus withsubsequent exfoliation (the Zumbusch pattern). This usually occurred in infancy and was difficult to control; recurrences developed several times per year. Three had the subacute benign annular pattern. They tended to be older and often had resolution within several years. Three had a mixed pattern with Zumbusch flares preceded by an annular or acral pattern. Most patients had an eruption preceding the generalized pustular psoriasis and often had precipitating factors. Generally, generalized pustular psoriasis has little serious chronic morbidity. The condition in most patients was well controlled with topical therapy. Systemic steroids were not helpful. (J AM ACAD DERMATOL 1991;24:186-94.)
Generalized pustular psoriasis is a rare form of psoriasis that is characterized by a widespread eruption of sterile pustules. Since its first description by von Zumbusch, l the clinical aspects of this disorder have been described in many case reports. 2·6 Several subgroups have been described, that is, acute generalized pustular psoriasis, circinate or annular pustular psoriasis, juvenile and infantile pustular psoriasis, and localized forms (not acral or palmoplantar).7 Of these subgroups, the juvenile and infantile variety is reported with the least frequency.8 Fewer than 100 cases of generalized pustular psoriasis in children have been reported, 9 and fewer than 50 cases have occurred within the first decade of life. 10 Generalized pustular psoriasis in this group differs from the adult-onset type in that it has no preceding psoriasis vulgaris. In approximately 30% ofinfantile cases a previous diagnosis of seborrheic or diaper dermatitis 9 has been made. We have identified 13 children with generalized pustular psoriasis younger than 18 years who were seen at the Mayo Clinic. A brief summary has been reported previously. 11
From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication July 5, 1990. Reprint requests: 8. A. Muller, MD, Mayo Clinic, 200 First 81. SW, Rochester, MN 55905.
16/1/23679
186
METHODS
The records of all patients with generalized pustular psoriasis who were seen at the Mayo Clinic during the 27 years from 1961 to 1988 were reviewed. Diagnostic criteria for selection included at least one well-documented episode of widespread macroscopic, noninfective, subcorneal pustulation before the age of 18 years. The data included patient identification, date of first and subsequent admissions for hospitalization, family history of psoriasis vulgaris and pustular psoriasis, past medical history, pattern of generalized flare (i.e., Zumbusch, annular, and mixed, according to the classification of Beylot et a1.9), history of previous psoriasis, precipitating factors, associated laboratory findings, symptoms, treatment, and complications. Biopsy specimens obtained from lesional skin were reviewed in each case.
RESULTS Thirteen patients with generalized pustular psoriasis were identified who fit the criteria for inclusion in this study (Table I). Ofthe thirteen patients, eight were examined at this institution before they were 13 years old. The average age at onset was 3.5 months (range 1 week to 8 months) in the six male patients and 8 years (range 8 months to 17 years) in the seven female patients. Seven of the patients (four male and three female), with an average age of 1 year (range 1 week to 15 years), had the Zumbusch pattern of generalized pustular psoriasis (Fig. I). Three of the patients (one male and two female), with an average age of 11 years (range 8 months to 17 years), had the annular type of generalized pustular psoriasis (Fig. 2). The three remaining patients (one male and two
Volume 24
Number2, Part 1 February 1991
Pustular psoriasis in childhood 187
Fig. 1. Case 4. A and B, Acute Zumbusch's flare occurring in an infant.
Fig. 2. Annular type of generalized pustular psoriasis with collarette scale and pustules at advancing edge.
female), age 2 months to 17 years, had a mixed type of generalized pustular psoriasis; patient 13 had an annular type of onset with episodes of acute Zumbusch-type flares, whereas patient 11 had Zumbusch flares at the age of 2 months that evolved into an acral variant by age 12 years. Three patients (cases 3, 8, and 10) had geographic tongue (Fig. 3). Biopsy specimens from lesional skin (stained with hematoxylin and eosin) of each patient had changes
consistent with pustular psoriasis, Alterations included acanthosis with elongation of rete ridges, parakeratosis, and spongiosis, with subcorneal and intraepidermal collections of neutrophils. During the acute flares, the patients were often ill, with high fever, malaise, anorexia, and pain secondary to their exfoliating skin. Despite this significant morbidity, however, each of the patients had a relatively benign course, and no deaths occurred.
Journal of the American Academy of Dermatology
188 Zelickson and Muller
Table I. Clinical data far 13 children (age 1 week ta 17 years) with generalized pustular psoriasis (GPP) Age at onset
Of preceding dermatitis
Systemic features
Case
Pattern ofGPP
Sex
OfGPP
1
z
M
1 wk
+
2
z
M
6 wk
+
+
I
M
2mo
4
z z
F
8mo
2wk
+
5
z
M
8mo
7mo
+
6
z
F
5 yr
6wk
+
7
z
F
15 yr
1 yr
+
8
A
M
8 mo
9
A
F
9 yr
10
A
F
17 yr
11
M
M
2mo
12
M
F
2.5 yr
13
M
F
3
17 yr
Family history of psoriasis
+
+ +
1 wk
8 yr (psoriasis vulgaris)
+
+
2wk 5 yr
+
A, Annular; GPP, generalized pustular psoriasis; M, mixed; PUVA, psoralen and ultraviolet A light; UVL, ultraviolet light; Z, Zumbusch.
Volume 24 Number 2, Part 1 February 1991
Pustular psoriasis in childhood 189
Treatment Precipitating factors
Winter
Sun, otitis, stress
Years of follow-up
39
2
Course
No generalized flares after 12 yr of age; developed localized patches of psoriasis vulgaris and pustular psoriasis Minimal localized pustular psoriasis, yet would break through with a generalized flare when drug tapered Continued flares, 1-2/yr
Tar, sun
17
Tar
17
Developed localized psoriasis vulgaris with a rare flare of
Streptococcal and staphylococcal infections
20
Tar, urinary tract and staphylococcal infections
10
Recurrent flares resembling staphylococcal scalded skin syndrome Continued flares,
Sun, milk
12
Sun, stress, pregnancy, surgery
52
Sun, tar
13
Urinary tract and upper respiratory infections Otitis, winter
27
Aspirin, urinary tract infection
19
3
GPP
1-2/yr
Went on to develop localized pustular psoriasis Recurrent flares, 2-3/yr, with clearing between Cleared at 12 yr of age; subsequently developed annular flares with each of two pregnancies, a cholecystectomy, and removal of ovarian cyst Currently free of disease
Effective
Inelfective
Topical corticosteroids
Sulfapyridine
Topical corticosteroids; etretinate
Systemic steroids; dapsone
Sulfapyridine; topical corticosteroids Topical corticosteroids
Sulfapyridine
Topical corticosteroids; etretinate Topical corticosteroids; PUVA UVL; topical corticosteroids
Dapsone; isotretinoin (Accutane); systemic corticosteroids Dapsone; sulfapyridine
Topical corticosteroids Topical corticosteroids
PUVA
Developed an acral pattern
Etretinate
Developed psoriasis vulgaris
Topical corticosteroids; tar preparations Modest improvement with systemic steroids, methotrexate, erythromycin
Recurrent Zumbusch and annular flares, 5-6/yr, for several years; currently, almost free of disease
I
Systemic corticosteroids; dapsone; UVL Systemic corticosteroids; dapsone UVL
Journal of the American Academy of Derma tology
190 Zelickson and .Muller
Fig. 3. Geographic tongue in a patient with generalized pustular psoriasis.
Laboratory evaluation revealed a leukocyte count of 20,300/mm3 (83% neutrophils) on admission and of 6000/mm3 at discharge. Antistreptolysin 0 titer was 1920 U (normal less than 170 U). Culture of a pustule grew Staphylococcus aureus and tl-hemolytic streptococcus group B. The patient was treated with moderate-strength topical steroids and etretinate (1 mg/kg). This was increased after 1 week (2 mg/kg) for 4 weeks and then tapered (to 1 mg/kg). Hewas also given a course of cefador (Cedor). This therapy controlled his disease for 2 years, but he had an exacerbation each time the dosage of etretinate was lowered.
Case 5 Fig. 4. Case 2. Marked nail dystrophy in a patient with
generalized pustular psoriasis.
SELECTED CASE REPORTS
Case 2 A 6-week-old white male patient developed a pustular eruption that generalized 4 weeks later. He had spontaneous clearing at 3 months of age and was clear until age 21 months, when he developed scaling and pustulation of the scalp associated with nail dystrophy (Fig. 4). Recurrences were precipitated by upper respiratory tract infections, otitis media, allergic reaction to amoxicillin, and sun exposure. He had no family history of psoriasis. Physical examination at age 7 years revealed a generalized pustular eruption with erythema. He had marked scaling and crusting of the scalp and prominent ungual pustulation.
This 7-month-old white male patient had a generalized dermatitis that clinically resembled seborrheic dermatitis. Two biopsy specimens were obtained; one had features of pityriasis rubra pilaris, and in the other there were similarities to psoriasis. The patient did well with moderatestrength topical steroids for the next 3 years, until he developed a generalized eruption that started 5 days after he was given oral penicillin for otitis media. He had complete clearing with moderate-strength topical steroids and antihistamines. Between the ages of 10 and 20 years, the patient had six episodes of generalized erythroderma associated with exfoliation (Fig. 5). The course of each episode was characterized by fever, malaise, headaches, diaphoresis, and skin tenderness, with total exfoliation and resolution within 2 to 3 weeks. The acute episodes were associated with an elevated temperature and a neutrophilia. Between each episode the patient remained completely clear. The patient had no family history of psoriasis or skin disease. On the patient's last admission at age 20 years, he had
Volume 24 Number 2, Part I February 1991
Pustular psoriasis in childhood 191
Fig. 5. Case 5. Exfoliation of axillary skin during an acute flare.
Fig. 6. Case 5. Pinpoint pustules on face.
a painful erythema and edema, most severe on the face, neck, and trunk, with little involvement of the distal extremities. He had a few pustules on his arms and face (Fig. 6). On the second and third days after admission, he developed numerous pustules and exfoliation of the trunk that progressed distally. With the exception of his palms and soles, exfoliation was complete in 4 days. During the acute episode of exfoliation, he was febrile and hypertensive. His leukocyte count was 23,600jmm3, with 85% neutrophils at the time of admission. A nasal culture grew S. aureus. The patient was treated with intravenous vancomycin for 4 days. Blood cultures and urine cultures were negative. A skin biopsy specimen showed subcorneal vesicles with typical spongiform pustular change charac-
teristic of generalized pustular psoriasis. He was almost completely clear 1 week after admission.
Case 6 This white female patient developed infantile eczema at 6 weeks of age. She had an acute onset of Zumbusch generalized pustular psoriasis at age 5 years. She was hospitalized at age 7 years for recurrent flares of generalized pustular psoriasis. She had no family history of psoriasis. Her recurrent flares were precipitated by urinary tract infections and upper respiratory tract infections and were associated with fever, leukocytosis, diffuse alopecia, loss of fingernails and toenails, and joint pains. Physical examination revealed an ill-appearing 7-
192 Zelickson and Muller
Journal of the American Academy of Dermatology
Fig. 7. Case 6. A and B, Generalized pustular psoriasis in a teenage gir1. year-old child with generalized, intense erythema with edema and 1 to 2 mm pustules on the arms, legs, abdomen, and back. The pustules in some areas coalesced to form lakes of pus. She also had scaling of the scalp and pitting of the fingernails. The palms, soles, and oral mucosa were not involved. She was treated with continuous wet dressings and a moderate-strength topical corticosteroid cream. She did not tolerate Goeckerman therapy. She subsequently responded well to moderate-strength topical steroids and ultraviolet B radiation. The patient was free of disease from age 9 until age 15 years, when she began having acute Zumbusch flares once per year (Fig. 7). These flares usually responded well in 2 to 3 weeks with hospitalization, continuous wet dressings, and moderate-strength topical steroid creams. At age 17 years she required prolonged hospitalization (64 days) because of a severe persistent flare of generalized pustular psoriasis. This flare was resistant to highdose systemic steroids, but it resolved completely with isotretinoin (Accutane) plus psoralen and ultraviolet A light (PUVA). The patient remained in remission when contacted 15 months later.
DISCUSSION Generalized pustular psoriasis is rare in childhood. In the largest series of 104 patients with generalized pustular psoriasis, only 5 were children. 7 When this disorder occurs in children, it often begins during the first year oflife,9, 12 but it can begin at any age during childhood. Unlike psoriasis vulgaris in childhood 13 and generalized pustular psoriasis in
adults,? childhood generalized pustular psoriasis affects male more than female children (ratio 3:2).9,14 Also, unlike the adult forms, childhood generalized pustular psoriasis tends to have a more benign course. 9 Psoriasis vulgaris occurs in more than 59% of patients with generalized pustular psoriasis, and 25% have a positive family history.9 In a report of 27 children with generalized pustular psoriasis, Beylot et a1. 9 classified their patients clinically into three groups: Zumbusch, annular, or mixed. The classic features of Zumbusch generalized pustular psoriasis consist of acute intermittent bouts of fever and toxicity associated with generalized flares of sterile pustules that resolve within 3 to 4 days, with recurrent waves of inflammation. 1, 4, 13 Most children with this pattern are between 2 and 10 years of age,4, 9, 14 yet the four infants described by Beylot et a1. 9 all had the Zumbusch type. These patients tend to develop psoriasis vulgaris. 9 In most cases of Zumbusch generalized pustular psoriasis the diagnosis can be made readily by clinical and histologic examination. The histology of pustular psoriasis is distinctive and may include the changes seen in psoriasis vulgaris: parakeratosis, elongation of the ridges, and deep, enlarged, spongiform pustules and Munro abscesses. 4 The diagnosis may not be so obvious, however, as exemplified by two of our patients (cases 2 and 5). The differential diagnosis of childhood generalized pustular psoriasis includes staphylococcal scalded skin syndrome,
Volume 24 Number 2, Part I February 1991
pityriasis rubra pilaris, toxic epidermal necrolysis, erythrodermic psoriasis, generalized seborrheic dermatitis, Reiter's disease, generalized candidiasis, and generalized atopic or seborrheic dermatitis. We recommend that children with generalized pustular psoriasis be treated with mild measures initially.9 The disease may not remit to mild temporizing measures, however, and more potent treatment may be necessary. Ryan and Baker l5 reported that systemic steroids were responsible for many of the serious long-term complications, whereas methotrexate was responsible for many of the minor short-term complications. The use of etretinate in eight children with widespread pustular psoriasis has previously been reported. 16-18 The ages of these children ranged from 8 months to 12.5 years, and the duration of treatment was up to 1 year. One patient had intermittent therapy for 2.3 years during a 4-year period. Generally these authors noted excellent results with no skeletal hyperostosis, early closure of epiphyses, or retardation in growth or development. Until more data are available, however, etretinate should be used cautiously in children. The teratogenicity, along with the prolonged half-life of etretinate, must be stressed when treating female patients who are of, or near, childbearing potential. Of our seven patients with Zumbusch-type flares, none treated with systemic steroids or dapsone improved. One of three patients treated with sulfapyridine had an initial response, and the condition was then controlled by hospitalization and treatment with topical steroids and wet dressings. This latter treatment was helpful in all cases. The one patient who did receive methotrexate did well for several years, yet had flares despite continued treatment. Three patients were given vitamin A derivatives orally: one had almost complete clearing with etretmate, one was given this medication recently and no follow-up data are available, and one had an initial favorable response to isotretinoin (Accutane) after systemic steroids and methotrexate failed. This patient then did well with PUVA. Annular generalized pustular psoriasis is less symptomatic and has a mild subacute to chronic course consisting of gyrate, annular lesions with an erythematous, scaly, pustular margin. 7 All children with the annular pattern described by Beylot et al. 9 were ages 2 to 10 years. They noted that generalized pustular psoriasis was of this pattern in approximately 30% of children. All the children described
Pustular psoriasis in childhood 193 by Baker and Ryan 7, 15 who had onset ofgeneralized pustular psoriasis before age 11 years had the annular pattern. In the report by Khan et al.,19 however, only 3 of 17 children had the annular pattern. Systemic symptoms may accompany flares of annular generalized pustular psoriasis,20 yet they tend to be milder than those accompanying the Zumbusch form. Three of our 13 patients (one male and two female) had the annular pattern. The average age was 11 years; only one patient developed it before 1 year of age. These patients generally had a preceding rash. Only one patient had documented systemic symptoms, yet she had a staphylococcal septicemia in conjunction with her documented fever and elevated leukocyte count. As with the Zumbusch group, most ofthese patients had similar precipitating factors. These patients tended to have a good response to soothing topical therapies. One patient had a good response to PUVA. Two of three patients treated with dapsone or sulfapyridine did not have benefit from this therapy. The patients tended to have fewer generalized flares with adolescence. The mixed type has both Zumbusch and annular patterns. This pattern can be seen in all age groups. In the series reported by Beylot et al., 9 all children younger than 1 year had this pattern-an initial Zumbusch flare that began with a seborrheic pattern and then became annular. In the series reported by Khan et al.,19 7 of 17 patients had this type, and more had onset before 1 year of age. Mild therapy is recommended in these patients. Three of our patients fit into this category. One had preceding psoriasis vulgaris until age 17 years, when she developed an acute Zumbusch flare with subsequent annular flares. The second patient is similar to one described by Leibiger and J acobi21 in that they were both male and had the Zumbusch type mixed with the acral form of pustular psoriasis. Our patient had a positive family history of generalized pustular psoriasis, and her disease was difficult to control with systemic steroids, dapsone, and etretinate. The third patient had one episode of generalized pustular psoriasis that developed from an annular pattern and then developed psoriasis vulgaris, which responded to conventional therapies. Although there were no deaths, four of our patients had complications during their hospitalization: three developed gram-positive septicemia, and one developed herpes simplex conjunctivitis.
Journal of the American Academy of Dermatology
194 Zelickson and Muller REFERENCES 1. von Zumbusch LR. Psoriasis und pustuloses Exanthem. Arch Dermatol Syph 1910;99:335-46. 2. Moslein P. Impetigo herpetiformis-psoriasis pustulosaacrodermatitis continua HalJopeau. Arch Klin Exp DermatoI1959;208:41O-58. 3. Kingery FA], Chinn HD, Saunders TS. Generalized pustular psoriasis. Arch DermatolI961;84:912-9. 4. Muller SA, Kitzmiller KW. Generalized pustular psoriasis: report of two cases. Acta Derm Venereol (Stockh) 1962; 42:504-12. 5. Lindgren S, Groth O. Generalized pustular psoriasis: a report on thirteen patients. Acta Derm Venereol (Stockh) 1976;56:139-47. 6. Murphy FR, Stolman LP. Generalized pustular psoriasis. Arch Dermatol 1979;115:1215-6. 7. Baker H, Ryan TJ. Generalized pustular psoriasis: a clinical and epidemiological study of 104 cases. Br J Dermatol 1968;80:771-93. 8. Baker H. Generalized pustular psoriasis. In: Roenigk HH Jr, Maibach HI, eds. Psoriasis. New York: Marcel Dekker, 1985:15. 9. Beylot C, Bioulac P, Grupper C, et aI. Generalized pustular psoriasis in infants and children: report of 27 cases. In: Farber EM, Cox AJ, Jacobs PH, et aI, eds. Psoriasis. New York: Yorke Medical Books, 1977:17I. 10. Hubler WR Jr. Familial juvenile generalized pustular psoriasis. Arch DermatoI1984;120:1174-8. II. Muller SA. Pustular psoriasis in children: report of I I cases.
12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
In: Farber EM, Nail ML, Morhenn V, et aI, eds. Psoriasis: Proceedings of the Fourth International Symposium, New York: Elsevier, 1987:410. Beylot C, Puissant A, Bioulac P, et aI. Particular clinical features of psoriasis in infants and children. Acta Derm Venereal [Suppl] (Stockh) 1979;87:95-7. Ogawa M, Baughman RD, Clendenning WE. Generalized pustular psoriasis: induction by topical use of coal tar. Arch DermatoI1969;99:671-3. Nyfors A. Psoriasis in children: characteristics, prognosis and therapy. A review. Acta Derm Venereal [Suppl] (Stockh) 1981 ;95:47-53. Ryan TJ, Baker H. The prognosis of generalized pustular psoriasis. Br J Dermatol 1971;85:407-11. Rosinska D, Wolska H, Jablonska S, et aI. Etretinate in severe psoriasis of children. Pediatr DermatoI1988;5:266-72. Shelnitz LS, Esterly NB, Honig PJ. Etretinate therapy for generalized pustular psoriasis in children. Arch Dermatol 1987;123:230-3. van de Kerkhof PCM. Generalized pustular psoriasis in a child. Dermatologica 1985;170:244-8. Khan SA, Peterkin GAG, Mitchell Pc. Juvenile generaljzed pustular psoriasis: a report of five cases and a review of the literature. Arch Dermatol 1972;105:67-72. Adler DJ, Rower JM, Hashimoto K. Annular pustular psoriasis. Arch Dermatol 1981;1I7:313. Leibiger C, Jacobi H. Psoriasis pustulosa vom Typ Zumbusch 1m Kindesalter. Hautarzt ]967;18:168.
BOUND VOLUMES AVAILABLE TO SUBSCRIBERS Bound volumes of the JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY are available to subscribers (only) for the 1991 issues from the Publisher ata cost of $60.00 ($78.00 international) for volume 24 (January-June) and volume 25 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Drive, S1. Louis, MO 63146-3318. USA: phone (800) 325-4177, ext. 4351. Subscriptions must be in force to qualify. Bound volumes are not available in place ofa regular journal subscription.
Generalized pustular psoriasis is a rare form of psoriasis that is characterized by a widespread eruption of sterile pustules. Since its first description by von Zumbusch, l the clinical aspects of this disorder have been described in many case reports. 2·6 Several subgroups have been described, that is, acute generalized pustular psoriasis, circinate or annular pustular psoriasis, juvenile and infantile pustular psoriasis, and localized forms (not acral or palmoplantar).7 Of these subgroups, the juvenile and infantile variety is reported with the least frequency.8 Fewer than 100 cases of generalized pustular psoriasis in children have been reported, 9 and fewer than 50 cases have occurred within the first decade of life. 10 Generalized pustular psoriasis in this group differs from the adult-onset type in that it has no preceding psoriasis vulgaris. In approximately 30% ofinfantile cases a previous diagnosis of seborrheic or diaper dermatitis 9 has been made. We have identified 13 children with generalized pustular psoriasis younger than 18 years who were seen at the Mayo Clinic. A brief summary has been reported previously. 11
From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication July 5, 1990. Reprint requests: 8. A. Muller, MD, Mayo Clinic, 200 First 81. SW, Rochester, MN 55905.
16/1/23679
186
METHODS
The records of all patients with generalized pustular psoriasis who were seen at the Mayo Clinic during the 27 years from 1961 to 1988 were reviewed. Diagnostic criteria for selection included at least one well-documented episode of widespread macroscopic, noninfective, subcorneal pustulation before the age of 18 years. The data included patient identification, date of first and subsequent admissions for hospitalization, family history of psoriasis vulgaris and pustular psoriasis, past medical history, pattern of generalized flare (i.e., Zumbusch, annular, and mixed, according to the classification of Beylot et a1.9), history of previous psoriasis, precipitating factors, associated laboratory findings, symptoms, treatment, and complications. Biopsy specimens obtained from lesional skin were reviewed in each case.
RESULTS Thirteen patients with generalized pustular psoriasis were identified who fit the criteria for inclusion in this study (Table I). Ofthe thirteen patients, eight were examined at this institution before they were 13 years old. The average age at onset was 3.5 months (range 1 week to 8 months) in the six male patients and 8 years (range 8 months to 17 years) in the seven female patients. Seven of the patients (four male and three female), with an average age of 1 year (range 1 week to 15 years), had the Zumbusch pattern of generalized pustular psoriasis (Fig. I). Three of the patients (one male and two female), with an average age of 11 years (range 8 months to 17 years), had the annular type of generalized pustular psoriasis (Fig. 2). The three remaining patients (one male and two
Volume 24
Number2, Part 1 February 1991
Pustular psoriasis in childhood 187
Fig. 1. Case 4. A and B, Acute Zumbusch's flare occurring in an infant.
Fig. 2. Annular type of generalized pustular psoriasis with collarette scale and pustules at advancing edge.
female), age 2 months to 17 years, had a mixed type of generalized pustular psoriasis; patient 13 had an annular type of onset with episodes of acute Zumbusch-type flares, whereas patient 11 had Zumbusch flares at the age of 2 months that evolved into an acral variant by age 12 years. Three patients (cases 3, 8, and 10) had geographic tongue (Fig. 3). Biopsy specimens from lesional skin (stained with hematoxylin and eosin) of each patient had changes
consistent with pustular psoriasis, Alterations included acanthosis with elongation of rete ridges, parakeratosis, and spongiosis, with subcorneal and intraepidermal collections of neutrophils. During the acute flares, the patients were often ill, with high fever, malaise, anorexia, and pain secondary to their exfoliating skin. Despite this significant morbidity, however, each of the patients had a relatively benign course, and no deaths occurred.
Journal of the American Academy of Dermatology
188 Zelickson and Muller
Table I. Clinical data far 13 children (age 1 week ta 17 years) with generalized pustular psoriasis (GPP) Age at onset
Of preceding dermatitis
Systemic features
Case
Pattern ofGPP
Sex
OfGPP
1
z
M
1 wk
+
2
z
M
6 wk
+
+
I
M
2mo
4
z z
F
8mo
2wk
+
5
z
M
8mo
7mo
+
6
z
F
5 yr
6wk
+
7
z
F
15 yr
1 yr
+
8
A
M
8 mo
9
A
F
9 yr
10
A
F
17 yr
11
M
M
2mo
12
M
F
2.5 yr
13
M
F
3
17 yr
Family history of psoriasis
+
+ +
1 wk
8 yr (psoriasis vulgaris)
+
+
2wk 5 yr
+
A, Annular; GPP, generalized pustular psoriasis; M, mixed; PUVA, psoralen and ultraviolet A light; UVL, ultraviolet light; Z, Zumbusch.
Volume 24 Number 2, Part 1 February 1991
Pustular psoriasis in childhood 189
Treatment Precipitating factors
Winter
Sun, otitis, stress
Years of follow-up
39
2
Course
No generalized flares after 12 yr of age; developed localized patches of psoriasis vulgaris and pustular psoriasis Minimal localized pustular psoriasis, yet would break through with a generalized flare when drug tapered Continued flares, 1-2/yr
Tar, sun
17
Tar
17
Developed localized psoriasis vulgaris with a rare flare of
Streptococcal and staphylococcal infections
20
Tar, urinary tract and staphylococcal infections
10
Recurrent flares resembling staphylococcal scalded skin syndrome Continued flares,
Sun, milk
12
Sun, stress, pregnancy, surgery
52
Sun, tar
13
Urinary tract and upper respiratory infections Otitis, winter
27
Aspirin, urinary tract infection
19
3
GPP
1-2/yr
Went on to develop localized pustular psoriasis Recurrent flares, 2-3/yr, with clearing between Cleared at 12 yr of age; subsequently developed annular flares with each of two pregnancies, a cholecystectomy, and removal of ovarian cyst Currently free of disease
Effective
Inelfective
Topical corticosteroids
Sulfapyridine
Topical corticosteroids; etretinate
Systemic steroids; dapsone
Sulfapyridine; topical corticosteroids Topical corticosteroids
Sulfapyridine
Topical corticosteroids; etretinate Topical corticosteroids; PUVA UVL; topical corticosteroids
Dapsone; isotretinoin (Accutane); systemic corticosteroids Dapsone; sulfapyridine
Topical corticosteroids Topical corticosteroids
PUVA
Developed an acral pattern
Etretinate
Developed psoriasis vulgaris
Topical corticosteroids; tar preparations Modest improvement with systemic steroids, methotrexate, erythromycin
Recurrent Zumbusch and annular flares, 5-6/yr, for several years; currently, almost free of disease
I
Systemic corticosteroids; dapsone; UVL Systemic corticosteroids; dapsone UVL
Journal of the American Academy of Derma tology
190 Zelickson and .Muller
Fig. 3. Geographic tongue in a patient with generalized pustular psoriasis.
Laboratory evaluation revealed a leukocyte count of 20,300/mm3 (83% neutrophils) on admission and of 6000/mm3 at discharge. Antistreptolysin 0 titer was 1920 U (normal less than 170 U). Culture of a pustule grew Staphylococcus aureus and tl-hemolytic streptococcus group B. The patient was treated with moderate-strength topical steroids and etretinate (1 mg/kg). This was increased after 1 week (2 mg/kg) for 4 weeks and then tapered (to 1 mg/kg). Hewas also given a course of cefador (Cedor). This therapy controlled his disease for 2 years, but he had an exacerbation each time the dosage of etretinate was lowered.
Case 5 Fig. 4. Case 2. Marked nail dystrophy in a patient with
generalized pustular psoriasis.
SELECTED CASE REPORTS
Case 2 A 6-week-old white male patient developed a pustular eruption that generalized 4 weeks later. He had spontaneous clearing at 3 months of age and was clear until age 21 months, when he developed scaling and pustulation of the scalp associated with nail dystrophy (Fig. 4). Recurrences were precipitated by upper respiratory tract infections, otitis media, allergic reaction to amoxicillin, and sun exposure. He had no family history of psoriasis. Physical examination at age 7 years revealed a generalized pustular eruption with erythema. He had marked scaling and crusting of the scalp and prominent ungual pustulation.
This 7-month-old white male patient had a generalized dermatitis that clinically resembled seborrheic dermatitis. Two biopsy specimens were obtained; one had features of pityriasis rubra pilaris, and in the other there were similarities to psoriasis. The patient did well with moderatestrength topical steroids for the next 3 years, until he developed a generalized eruption that started 5 days after he was given oral penicillin for otitis media. He had complete clearing with moderate-strength topical steroids and antihistamines. Between the ages of 10 and 20 years, the patient had six episodes of generalized erythroderma associated with exfoliation (Fig. 5). The course of each episode was characterized by fever, malaise, headaches, diaphoresis, and skin tenderness, with total exfoliation and resolution within 2 to 3 weeks. The acute episodes were associated with an elevated temperature and a neutrophilia. Between each episode the patient remained completely clear. The patient had no family history of psoriasis or skin disease. On the patient's last admission at age 20 years, he had
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Pustular psoriasis in childhood 191
Fig. 5. Case 5. Exfoliation of axillary skin during an acute flare.
Fig. 6. Case 5. Pinpoint pustules on face.
a painful erythema and edema, most severe on the face, neck, and trunk, with little involvement of the distal extremities. He had a few pustules on his arms and face (Fig. 6). On the second and third days after admission, he developed numerous pustules and exfoliation of the trunk that progressed distally. With the exception of his palms and soles, exfoliation was complete in 4 days. During the acute episode of exfoliation, he was febrile and hypertensive. His leukocyte count was 23,600jmm3, with 85% neutrophils at the time of admission. A nasal culture grew S. aureus. The patient was treated with intravenous vancomycin for 4 days. Blood cultures and urine cultures were negative. A skin biopsy specimen showed subcorneal vesicles with typical spongiform pustular change charac-
teristic of generalized pustular psoriasis. He was almost completely clear 1 week after admission.
Case 6 This white female patient developed infantile eczema at 6 weeks of age. She had an acute onset of Zumbusch generalized pustular psoriasis at age 5 years. She was hospitalized at age 7 years for recurrent flares of generalized pustular psoriasis. She had no family history of psoriasis. Her recurrent flares were precipitated by urinary tract infections and upper respiratory tract infections and were associated with fever, leukocytosis, diffuse alopecia, loss of fingernails and toenails, and joint pains. Physical examination revealed an ill-appearing 7-
192 Zelickson and Muller
Journal of the American Academy of Dermatology
Fig. 7. Case 6. A and B, Generalized pustular psoriasis in a teenage gir1. year-old child with generalized, intense erythema with edema and 1 to 2 mm pustules on the arms, legs, abdomen, and back. The pustules in some areas coalesced to form lakes of pus. She also had scaling of the scalp and pitting of the fingernails. The palms, soles, and oral mucosa were not involved. She was treated with continuous wet dressings and a moderate-strength topical corticosteroid cream. She did not tolerate Goeckerman therapy. She subsequently responded well to moderate-strength topical steroids and ultraviolet B radiation. The patient was free of disease from age 9 until age 15 years, when she began having acute Zumbusch flares once per year (Fig. 7). These flares usually responded well in 2 to 3 weeks with hospitalization, continuous wet dressings, and moderate-strength topical steroid creams. At age 17 years she required prolonged hospitalization (64 days) because of a severe persistent flare of generalized pustular psoriasis. This flare was resistant to highdose systemic steroids, but it resolved completely with isotretinoin (Accutane) plus psoralen and ultraviolet A light (PUVA). The patient remained in remission when contacted 15 months later.
DISCUSSION Generalized pustular psoriasis is rare in childhood. In the largest series of 104 patients with generalized pustular psoriasis, only 5 were children. 7 When this disorder occurs in children, it often begins during the first year oflife,9, 12 but it can begin at any age during childhood. Unlike psoriasis vulgaris in childhood 13 and generalized pustular psoriasis in
adults,? childhood generalized pustular psoriasis affects male more than female children (ratio 3:2).9,14 Also, unlike the adult forms, childhood generalized pustular psoriasis tends to have a more benign course. 9 Psoriasis vulgaris occurs in more than 59% of patients with generalized pustular psoriasis, and 25% have a positive family history.9 In a report of 27 children with generalized pustular psoriasis, Beylot et a1. 9 classified their patients clinically into three groups: Zumbusch, annular, or mixed. The classic features of Zumbusch generalized pustular psoriasis consist of acute intermittent bouts of fever and toxicity associated with generalized flares of sterile pustules that resolve within 3 to 4 days, with recurrent waves of inflammation. 1, 4, 13 Most children with this pattern are between 2 and 10 years of age,4, 9, 14 yet the four infants described by Beylot et a1. 9 all had the Zumbusch type. These patients tend to develop psoriasis vulgaris. 9 In most cases of Zumbusch generalized pustular psoriasis the diagnosis can be made readily by clinical and histologic examination. The histology of pustular psoriasis is distinctive and may include the changes seen in psoriasis vulgaris: parakeratosis, elongation of the ridges, and deep, enlarged, spongiform pustules and Munro abscesses. 4 The diagnosis may not be so obvious, however, as exemplified by two of our patients (cases 2 and 5). The differential diagnosis of childhood generalized pustular psoriasis includes staphylococcal scalded skin syndrome,
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pityriasis rubra pilaris, toxic epidermal necrolysis, erythrodermic psoriasis, generalized seborrheic dermatitis, Reiter's disease, generalized candidiasis, and generalized atopic or seborrheic dermatitis. We recommend that children with generalized pustular psoriasis be treated with mild measures initially.9 The disease may not remit to mild temporizing measures, however, and more potent treatment may be necessary. Ryan and Baker l5 reported that systemic steroids were responsible for many of the serious long-term complications, whereas methotrexate was responsible for many of the minor short-term complications. The use of etretinate in eight children with widespread pustular psoriasis has previously been reported. 16-18 The ages of these children ranged from 8 months to 12.5 years, and the duration of treatment was up to 1 year. One patient had intermittent therapy for 2.3 years during a 4-year period. Generally these authors noted excellent results with no skeletal hyperostosis, early closure of epiphyses, or retardation in growth or development. Until more data are available, however, etretinate should be used cautiously in children. The teratogenicity, along with the prolonged half-life of etretinate, must be stressed when treating female patients who are of, or near, childbearing potential. Of our seven patients with Zumbusch-type flares, none treated with systemic steroids or dapsone improved. One of three patients treated with sulfapyridine had an initial response, and the condition was then controlled by hospitalization and treatment with topical steroids and wet dressings. This latter treatment was helpful in all cases. The one patient who did receive methotrexate did well for several years, yet had flares despite continued treatment. Three patients were given vitamin A derivatives orally: one had almost complete clearing with etretmate, one was given this medication recently and no follow-up data are available, and one had an initial favorable response to isotretinoin (Accutane) after systemic steroids and methotrexate failed. This patient then did well with PUVA. Annular generalized pustular psoriasis is less symptomatic and has a mild subacute to chronic course consisting of gyrate, annular lesions with an erythematous, scaly, pustular margin. 7 All children with the annular pattern described by Beylot et al. 9 were ages 2 to 10 years. They noted that generalized pustular psoriasis was of this pattern in approximately 30% of children. All the children described
Pustular psoriasis in childhood 193 by Baker and Ryan 7, 15 who had onset ofgeneralized pustular psoriasis before age 11 years had the annular pattern. In the report by Khan et al.,19 however, only 3 of 17 children had the annular pattern. Systemic symptoms may accompany flares of annular generalized pustular psoriasis,20 yet they tend to be milder than those accompanying the Zumbusch form. Three of our 13 patients (one male and two female) had the annular pattern. The average age was 11 years; only one patient developed it before 1 year of age. These patients generally had a preceding rash. Only one patient had documented systemic symptoms, yet she had a staphylococcal septicemia in conjunction with her documented fever and elevated leukocyte count. As with the Zumbusch group, most ofthese patients had similar precipitating factors. These patients tended to have a good response to soothing topical therapies. One patient had a good response to PUVA. Two of three patients treated with dapsone or sulfapyridine did not have benefit from this therapy. The patients tended to have fewer generalized flares with adolescence. The mixed type has both Zumbusch and annular patterns. This pattern can be seen in all age groups. In the series reported by Beylot et al., 9 all children younger than 1 year had this pattern-an initial Zumbusch flare that began with a seborrheic pattern and then became annular. In the series reported by Khan et al.,19 7 of 17 patients had this type, and more had onset before 1 year of age. Mild therapy is recommended in these patients. Three of our patients fit into this category. One had preceding psoriasis vulgaris until age 17 years, when she developed an acute Zumbusch flare with subsequent annular flares. The second patient is similar to one described by Leibiger and J acobi21 in that they were both male and had the Zumbusch type mixed with the acral form of pustular psoriasis. Our patient had a positive family history of generalized pustular psoriasis, and her disease was difficult to control with systemic steroids, dapsone, and etretinate. The third patient had one episode of generalized pustular psoriasis that developed from an annular pattern and then developed psoriasis vulgaris, which responded to conventional therapies. Although there were no deaths, four of our patients had complications during their hospitalization: three developed gram-positive septicemia, and one developed herpes simplex conjunctivitis.
Journal of the American Academy of Dermatology
194 Zelickson and Muller REFERENCES 1. von Zumbusch LR. Psoriasis und pustuloses Exanthem. Arch Dermatol Syph 1910;99:335-46. 2. Moslein P. Impetigo herpetiformis-psoriasis pustulosaacrodermatitis continua HalJopeau. Arch Klin Exp DermatoI1959;208:41O-58. 3. Kingery FA], Chinn HD, Saunders TS. Generalized pustular psoriasis. Arch DermatolI961;84:912-9. 4. Muller SA, Kitzmiller KW. Generalized pustular psoriasis: report of two cases. Acta Derm Venereol (Stockh) 1962; 42:504-12. 5. Lindgren S, Groth O. Generalized pustular psoriasis: a report on thirteen patients. Acta Derm Venereol (Stockh) 1976;56:139-47. 6. Murphy FR, Stolman LP. Generalized pustular psoriasis. Arch Dermatol 1979;115:1215-6. 7. Baker H, Ryan TJ. Generalized pustular psoriasis: a clinical and epidemiological study of 104 cases. Br J Dermatol 1968;80:771-93. 8. Baker H. Generalized pustular psoriasis. In: Roenigk HH Jr, Maibach HI, eds. Psoriasis. New York: Marcel Dekker, 1985:15. 9. Beylot C, Bioulac P, Grupper C, et aI. Generalized pustular psoriasis in infants and children: report of 27 cases. In: Farber EM, Cox AJ, Jacobs PH, et aI, eds. Psoriasis. New York: Yorke Medical Books, 1977:17I. 10. Hubler WR Jr. Familial juvenile generalized pustular psoriasis. Arch DermatoI1984;120:1174-8. II. Muller SA. Pustular psoriasis in children: report of I I cases.
12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
In: Farber EM, Nail ML, Morhenn V, et aI, eds. Psoriasis: Proceedings of the Fourth International Symposium, New York: Elsevier, 1987:410. Beylot C, Puissant A, Bioulac P, et aI. Particular clinical features of psoriasis in infants and children. Acta Derm Venereal [Suppl] (Stockh) 1979;87:95-7. Ogawa M, Baughman RD, Clendenning WE. Generalized pustular psoriasis: induction by topical use of coal tar. Arch DermatoI1969;99:671-3. Nyfors A. Psoriasis in children: characteristics, prognosis and therapy. A review. Acta Derm Venereal [Suppl] (Stockh) 1981 ;95:47-53. Ryan TJ, Baker H. The prognosis of generalized pustular psoriasis. Br J Dermatol 1971;85:407-11. Rosinska D, Wolska H, Jablonska S, et aI. Etretinate in severe psoriasis of children. Pediatr DermatoI1988;5:266-72. Shelnitz LS, Esterly NB, Honig PJ. Etretinate therapy for generalized pustular psoriasis in children. Arch Dermatol 1987;123:230-3. van de Kerkhof PCM. Generalized pustular psoriasis in a child. Dermatologica 1985;170:244-8. Khan SA, Peterkin GAG, Mitchell Pc. Juvenile generaljzed pustular psoriasis: a report of five cases and a review of the literature. Arch Dermatol 1972;105:67-72. Adler DJ, Rower JM, Hashimoto K. Annular pustular psoriasis. Arch Dermatol 1981;1I7:313. Leibiger C, Jacobi H. Psoriasis pustulosa vom Typ Zumbusch 1m Kindesalter. Hautarzt ]967;18:168.
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