ARTICLE
Acute generalized exanthematous pustulosis (AGEP) resembles generalized
pustular psoriasis, but may manifest targetoid lesions, purpura, and blisters
in addition to pustules. We describe a case of AGEP with erythema multiforme
(EM)-like features in a 35-year-old woman who presented with acute onset
of high fever and a strikingly polymorphic eruption consisting of numerous
tiny pustules on erythematous bases, marked facial edema, oral and genital
erosions, targetoid vesicular and purpuric lesions, pustules in string-of-pearl
configuration and ring-like vesicles. The histology revealed, in addition
to subcorneal pustules, vacuolar interface dermatitis with involvement
of eccrine glands, and microabscesses in pilosebaceous structures. Systemic
corticorsteroid and antibiotics were initiated, resulting in rapid resolution
without recurrence. Recognition of EM-like lesions on a background of
generalized pustular eruption could facilitate the diagnosis of AGEP and
the institution of appropriate treatment.
Key words: acute generalized exanthematous pustulosis, eosinophils,
erythema multiforme major, pustular psoriasis.
In the past, most generalized sterile pustular eruptions were classified
as von Zumbusch type generalized pustular psoriasis (GPP). In 1968, Baker
and Ryan identified, from 104 patients with GPP, 5 cases of "exanthematous
pustular psoriasis" which ran short self-limiting courses and were thought
to be precipitated by infections and/or drugs [1]. In 1980, Beylot et
al. termed this disorder "acute generalized exanthematous pustulosis"
(AGEP) [2]. Roujeau et al. analyzed 63 cases of AGEP and proposed
a set of diagnostic criteria [3]. Clinically, AGEP is characterized by
acute onset of fever and a rapidly progressive non-follicular pinhead-sized
sterile pustular eruption on an erythematous background, and a short self-healing
course [3]. Clinically AGEP resembles GPP, but it may be distinguished
from GPP by pseudo-erythema multiforme (pseudo-EM) lesions, purpura, edema,
blisters, and mucosal erosions which were found in 25 to 33% of the cases
of AGEP [3]. Most cases of AGEP were induced by drugs, particularly antibiotics.
But a few cases were related to viral infections or other factors, or
without an identifiable etiology [3]. Histology of AGEP shows pustules
and papillary edema. In addition, eosinophils in the infiltrate, leukocytoclastic
vasculitis and focal necrosis of keratinocytes have been found in 34%,
20% and 25% of the biopsy specimens, respectively [3].
We report a case of AGEP with very polymorphic clinical and pathologic
features that looked like a hybrid of EM major and GPP.
Case report
A 35-year-old woman was admitted for a generalized pruritic eruption
in association with spiking fever and chills for 2 days and oral and genital
erosions for 1 day. The rash was preceded by a sore throat for a few days.
She had a history of drug-induced fulminant hepatitis about 4 years previously
and had since been taking two herbal drugs.
On admission, the patient had a temperature 40.7° C. Physical examination
revealed marked facial swelling, conjunctival congestion (Fig. 1A),
oral and genital erosions, widespread solitary or coalescing pustules
and bean-sized edematous targetoid lesions (Fig. 1B), some of which
were studded with tiny pustules or vesicles in the center or at the periphery
(Fig. 2A, B).
Hemogram revealed a leukocyte count of 12 x 109 L-
1 with 8% band and 84% segments. Urinalysis showed WBC 35 per high
power field, suggestive of a urinary tract infection. A Tzanck smear and
bacterial cultures of a pustule, blood and urine yielded negative results.
Results of other laboratory tests, including routine blood biochemistry,
anti-streptolysin O, C3, C4, ANA, VDRL, cryoprotein, serum electrophoresis
and immunoelectrophoresis, mycoplasma antibody (Ab), anti-herpes simplex
virus 1 and 2 IgM, hepatitis B surface (HBs) antigen, anti-HBs Ab, anti-HB
core IgM, anti-hepatitis C Ab, and anti-HIV Ab were either negative or
within normal limits.
The patient was treated with intravenous methylprednisolone 40 mg daily
for 6 days followed by 20 mg daily for 4 days and 10 mg daily for 2 days.
A short course of antibiotics, including amoxicillin/clavulanic acid and
gentamicin was given for the suspected urinary tract infection, and cyproheptadine
4 mg to 8 mg qid and doxepin 25 mg hrs for the severe pruritus. The spiking
fever lasted for 2 days accompanied by rapid progression of the skin lesions
with numerous tiny pustules which appeared on the face (Fig. 1C),
chest and forearms (Fig. 2C). New crops of edematous targetoid
lesions and vesicles appeared on the hands. The targetoid lesions on the
lower extremities became purpuric (Fig. 1D) while some in other
areas became ring-like vesicles (Fig. 2D). Dramatic clinical improvement
was noted starting from day 4. The rash almost completely resolved by
day 10, leaving behind extensive desquamation. The patient was discharged
on day 13 on prednisolone 10 mg bid, which was discontinued later with
no recurrence of skin eruption while she resumed taking previous herbal
drugs.
Biopsy was performed on a targetoid lesion on day 1 and a pustule on
day 3. The targetoid lesion showed vacuolar interface dermatitis with
occasional necrotic keratinocytes and infiltration of lymphocytes in the
lower part of epidermis and edematous papillary dermis. In addition, there
was a moderately dense superficial and deep perivascular and periadnexal
infiltrate of lymphocytes and eosinophils with involvement of hair follicles
and eccrine secretory coils. The second biopsy revealed subcorneal and
intraepidermal pustules, spongiosis, vacuolar alteration of basal cells
and necrotic keratinocytes in the epidermis (Fig. 3). In addition,
microabscesses were noted within some follicles and sebaceous glands.
A moderately dense perivascular and interstitial infiltrate of lymphocytes,
histiocytes, neutrophils and many eosinophils was present in the dermis,
and focally involved sweat coils, ducts and acrosyringia. No evidence
of vasculitis was observed in either biopsy specimen.
Discussion
The clinical and pathologic features of the present case satisfy the
diagnostic criteria of AGEP proposed by Roujeau et al. In addition
to solitary or coalescing pustules on erythematous bases, pseudo-EM targetoid
lesions, purpura and marked edema, there were target lesions of typical
EM type with 3 rings, string-of-pearl pustules, ring-like vesicles and
extensive mucosal erosions. Pseudo-EM lesions have been observed in 24%
of the AGEP cases [3]; they were "atypical" target lesions with only two
rings. Histologically, the findings of intraepidermal and subcorneal pustules,
necrotic keratinocytes, dermal edema and an eosinophil-rich infiltrate
were consistent with AGEP. However, pustules or microabscesses also involved
hair follicles and sebaceous glands. These findings were unusual in AGEP,
but follicular pustules have been described previously by Burrows &
Jones [4] and Gebauer et al. [5].
Although the majority of the cases of AGEP are drug-induced in a large
series, in about 5% of the cases no etiology could be attributed [3].
The cause of AGEP in our patient remained obscure. The laboratory data
failed to substantiate a preceding infection, although an upper respiratory
tract infection could not be completely excluded. The clinical and histologic
findings were rather complex and did not conform to a specific disease,
and thus would favor a drug eruption. However, we could not identify a
suspicious drug. The drugs used during hospitalization were initiated
after onset of AGEP. The two herbal drugs of unknown nature appeared unlikely
to be the culprit because she had been taking them for years and took
them again after AGEP uneventfully.
The clinical and pathologic findings of AGEP should be differentiated
from EM major and GPP. The important differentiating features are listed
in Table I. Although some of the clinical and pathologic changes
in the present case suggested EM, the findings of eosinophil-rich infiltrate
and subcorneal pustules appear inconsistent with that diagnosis. Subcorneal
pustules are very rare in EM, and have been described in only a single
case [6]. However, the histopathologic findings described in that case
lacked basal vacuolar alteration and necrosis of keratinocytes, the characteristic
feature of EM.
AGEP can usually be differentiated from GPP by its polymorphic eruption
which is characterized by generalized pustular eruptions with targetoid,
vesicular, purpuric or/and mucosal lesions, and a short, self-limited
course clinically. Histologically, GPP does not exhibit vacuolar interface
change, necrotic keratinocytes or inflammation of sweat glands or/and
sebaceous glands. Targetoid lesions are occasionally observed in linear
IgA bullous dermatosis [7], Behçet's disease [8], neutrophilic
dermatoses [9], and Kawasaki's disease [10]. Subcorneal pustules are seen
in staphylococcal scalded skin syndrome, Sneddon-Wilkinson syndrome [11],
IgA pemphigus [12], and impetigo contagiosum. However, the combination
of clinical and histopathologic findings makes these dermatoses unlikely
in the present case.
In conclusion, we report an interesting case of AGEP with prominent
EM-like features. Recognition of EM-like lesions in a background of generalized
pustular eruption would facilitate the diagnosis of AGEP and institution
of appropriate treatment.
References
1. Baker H, Ryan TJ. Generalized pustular psoriasis: a clinical
and epidemiological study of 104 cases. Br J Dermatol 1968; 80:
771-93.
2. Beylot C, Bioulac P, Doutre MS. Pustuloses exanthématiques
aiguës généralisées: à propos de 4 cas.
Ann Dermatol Venereol 1980; 107: 37-48.
3. Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard
P, Lok C, Plantin P, Claudy A, Delavierre C, Vaillant L, Wechsler J, Danan
G, Bénichou C, Beylot C. Acute generalized exanthematous pustulosis.
Analysis of 63 cases. Arch Dermatol 1991; 127: 1333-8.
4. Burrows NP, Jones RR. Pustular drug eruptions: a histopathological
spectrum. Histopathology 1993; 22: 569-73.
5. Gebauer K, Holgate C, Navaratnam A. Toxic pustuloderma: a
drug induced pustulating glandular fever-like syndrome. Australas J
Dermatol 1990; 31: 89-93.
6. Sneddon IB. Subcorneal pustules in erythema multiforme. Br
J Dermatol 1973; 88: 605-7.
7. Argenyi ZB, Bergfeld WF, Valenzuela R, Mcmahon JT, Tomecki
KJ. Linear IgA bullous dermatosis mimicking erythema multiforme in adult.
Int J Dermatol 1987; 26: 513-7.
8. Lee ES, Band D, Lee S. Dermatologic manifestation of Behçet's
disease. Yonsei Med J 1997; 38: 380-9.
9. Vignon-Pennamen MD, Wallach D. Cutaneous manifestation of
neutrophilic disease: a study of seven cases. Dermatologica 1991;
183: 255-64.
10. Bitter JJ, Friedman SA, Paltzik RL, Mofenson HC. Kawasaki's
disease appearing as erythema multiforme. Arch Dermatol 1979; 115:
71-2.
11. Sneddon IB, Wilkinson DS. Subcorneal pustular dermatosis.
Br J Dermatol 1956; 68: 385-94.
12. Robinson ND, Hashimoto T, Amagai M, Chan LS. The new pemphigus
variants. J Am Acad Dermatol 1999; 40: 649-71.
Article accepted on 27/5/02
|
|
|
|
Figure 1. Polymorphous
eruption of AGEP. On day 1, the patient presented with marked facial
swelling with some pustules, and injected conjunctivae (A),
and numerous edematous targetoid lesions on the legs (B). One
day 3, numerous pustules were noted on the face (C), and purpuric
change of targetoid lesions on the legs (D). |
|
|
|
|
|
Figure 2. Some target
lesions were studded with tiny vesicles (A), or pustules (B)
on day 1. One day 3, some lesions developed string-of-pearl like pustules
(C), or ring-like vesicles (D). |
|
|
|
|
|
Figure 3. The histopathology
of a pustule revealed subcorneal and intraepidermal pustules and a
moderately dense perivascular and interstitial infiltrate of lymphocytes,
histiocytes, neutrophils and many eosinophils in the upper dermis
(A). A close-up view showed spongiosis and vacuolar alteration
of basal cells in the epidermis (B) (HE stain, A x 40, B x
200). |
|
|
Version imprimable