intensive topical regimen of corticosteroid ointment and
greasy emollient. Over the next 2 days, the pustules
resolved with pinpoint desquamation. The renal function
followed a parallel course and returned to baseline after
AGEP is a severe cutaneous adverse reaction caused by
drug hypersensitivity, the most common culprits being
antibiotics, especially aminopenicillins.
In contrast to
Stevens–Johnson syndrome/toxic epidermal necrolysis
and drug reaction with eosinophilia and systemic symp-
toms, systemic involvement in AGEP is usually not prom-
inent. In a retrospective study of 58 cases of AGEP
collected over a 10-year period, 17% had internal organ
involvement, including liver, kidney, bone marrow and
In that study, 6 of the 58 patients developed renal
impairment, but with only mild and transient renal
insufﬁciency, ranging from 1.5 to 2.3 fold increase in
creatinine from baseline. In our patient, AGEP was
accompanied by severe renal impairment, classiﬁed by
stage 3 AKI.
During the ﬁrst 72 hours of the acute illness, our
patient’s blood pressure was well-maintained despite the
deteriorating renal function, which would argue against
a pre-renal insult. The absence of signiﬁcant proteinuria,
along with an eosinophilia, indicates interstitial nephritis
would explain the renal injury.
It is recognized that T helper 17 cells have a contribu-
tory role in the development of AGEP via the release of
interleukin (IL)-22, leading to CXCL8 upregulation and
IL-22 receptors are expressed in
the kidney, and activation of this pathway may explain
renal involvement in AGEP.
Internal organ involvement in AGEP is perhaps more
prominent than has been recognized in the past. Poten-
tially life-threatening renal injury needs to be considered
in patients presenting with drug-induced pustuloderma.
, S. Walsh
, T. Basu
and D. Creamer
Department of Dermatology, King’s College Hospital, Denmark Hill,
London, SE5 9RS, UK
Conﬂict of interest: the authors declare that they have no conﬂicts of
Accepted for publication 8 April 2017
1 Sidoroff A, Dunant A, Viboud C et al. Risk factors for
acute generalized exanthematous pustulosis (AGEP)—
results of a multinational case-control study (EuroSCAR).
Br J Dermatol 2007; 157: 989–96.
2 Hotz C, Valeyrie-Allanore L, Haddad C et al. Systemic
involvement of acute generalized exanthematous
pustulosis: a retrospective study on 58 patients. Br J
Dermatol 2013; 169: 1223–32.
3 Kabashima R, Sugita K, Sawada Y et al. Increased
circulating Th17 frequencies and serum IL-22 levels in
patients with acute generalized exanthematous pustulosis.
J Eur Acad Dermatol Venereol 2011; 25: 485–8.
Coexistence of pemphigus herpetiformis with
extramammary Paget disease
Few clinical cases of pemphigus herpetiformis (PH) associ-
ated with neoplasia have been reported.
We describe the
ﬁrst case, to our knowledge, of simultaneous PH and
extramammary Paget disease (EMPD).
A 72-year-old man presented with a 6-month history
of diffuse erythema, papules, vesicles and bullae, some
of which were annular in shape (Fig. 1a), and an
erythematous skin rash with exudation and ulcers on
the scrotum and base of the penis (Fig. 2a). All lesions
were severely pruritic. Nikolsky sign was negative.
The mucous membranes were clear, and no lym-
phadenopathy was found. Radiographs of the chest
were clear, and colonoscopy and ultrasonography
ﬁndings of the abdominal and uropoietic systems were
Histopathological examination of a biopsy specimen
taken from the right thigh revealed neutrophilic and
eosinophilic spongiosis, and an intraepidermal vesicle
containing neutrophils and eosinophils (Fig. 1). A biopsy
specimen from the scrotum revealed large, round cells
with ample amphophilic cytoplasm (Fig. 2).
Immunohistochemically, the cells were positive for
cytokeratin (CK)7, epithelial membrane antigen and
HER-2, and negative for CK20 and gross cystic disease
ﬂuid protein (GCDFP)-15 (Fig. 2). Direct immunoﬂuores-
cence of the thigh biopsy specimen showed deposition of
IgG and C3 on the surface of the keratinocytes (Fig. 1).
Indirect immunoﬂuorescence showed a positive desmo-
glein (Dsg)1 titre of 232.0 IU/mL (normal < 20 IU/mL),
and that the Dsg3 titre was negative (positive: ≥ 20 IU/
Based on the clinical features and histopathological
ﬁndings, a diagnosis of the coexistence of PH with
EMPD was made. Because dapsone is not available in
our hospital, methylprednisolone was started at 56 mg/
day and gradually reduced according to the patient’s
symptoms. Wide surgical excision of the lesion on the
scrotum and base of the penis was advised, but the
patient refused further treatment. He has been followed
up over a period of 16 months, and during this time,
no relapse of the PH or invasion of the EMPD have
PH is an uncommon autoimmune vesiculobullous
disease. Jablonska et al.
ﬁrst established the diagnostic
criteria of PH in 1975. All clinical and pathological
features in the present case met the diagnostic criteria
ª 2017 British Association of Dermatologists
Clinical and Experimental Dermatology (2018) 43, pp319–335