index finger of a healthy woman showing intraepidermal
blisters [5]. Histopathologically, the lesion shows intraepi-
dermal blisters containing degenerated keratinocytes and
multinucleated giant cells. Another case is herpetic syco-
sis without epidermal damage in a Burkitt lymphoma
patient [6]. In our case, atypical herpes zoster presented
as a solitary vesicular lesion, and histopathologically,
VZV infection was observed both in epithelial cells and
hair follicles. It was also interesting that the skin lesion in
our case was persistent in spite of antiviral treatment and
that the anti-VZV antibody titer was not elevated.
Hematopoietic disorder and anti-CD20 antibody therapy
might be the reason why such an atypical lesion occurred
in this case.
■
Acknowledgements. Funding sources: none. Conflicts of
interest: none.
Department of Dermatology, Aichi
medical University, Nagakute,
Aichi, 480-1195 Japan D. Watanabe
<dwatanab@aichi-med-u.ac.jp>
Natsuko ISHIDA
Daisuke WATANABE
Tomoe KUHARA
Hiromichi TAKAMA
Yasuhiko TAMADA
Yoshinari
MATSUMOTO
1.Dı
´
az-Ramo
´
n JL, Dı
´
az-Pe
´
rez JL. Herpes simplex and zoster. Eur
J Dermatol 2008; 18: 108-11.
2. Ahmed AM, Brantley JS, Madkan V, Mendoza N, Tyring SK. Man-
aging herpes zoster in immunocompromised patients. Herpes 2007;
14: 32-6.
3.Bo
¨
er A, Herder N, Winter K, Falk T. Herpes folliculitis: clinical,
histopathological, and molecular pathologic observations. Br J Der-
matol 2006; 154: 743-6.
4. Sangueza OP, Gordon MD, White Jr. CR. Subtle clues to the diag-
nosis of the herpesvirus by light microscopy. Herpetic syringitis. Am
J Dermatopathol 1995; 17: 163-8.
5. Izu K, Yamamoto O, Yasumoto S, Hashimoto T, Sata T, Tokura Y.
Herpes zoster occurring as a solitary nodule on the index finger. Br
J Dermatol 2004; 150: 365-6.
6. Alonso-Pe
´
rez A, Fraga J, Delgado Y, Aragu
¨
e
´
s M, Nam-Cha S,
Garcı
´
a-Dı
´
ez A. Nodular herpes zoster with herpetic syringitis and
no epidermal involvement in a patient with Burkitt lymphoma. Am
J Dermatopathol 2006; 28: 194-6.
doi:10.1684/ejd.2009.0655
Patch-type granuloma annulare
A 74-year-old white woman was referred to our depart-
ment with a 1-year history of four large asymptomatic
lesions on her thighs. The lesions began as small erythe-
matous patches and subsequently increased in diameter.
She had a history of arthritis, treated for the preceding 3
years with naproxen.
Examination of the posterior thighs revealed four large
(between 3 × 2 cm and 17 × 14 cm) erythematous, mini-
mally scaly, oval patches, with no induration. One of the
lesions had light central clearing (figure 1). Physical exa-
mination was otherwise unremarkable. The initial clinical
impression was parapsoriasis, and a biopsy specimen was
obtained. Histopathological examination revealed a mode-
rate superficial and mid-dermal interstitial infiltrate of
lymphocytes and histiocytes, and mucin between collagen
fibers; these findings are consistent with the interstitial
variant of granuloma annulare. Further investigations
were unremarkable. The diagnosis of patch-type granulo-
ma annulare was made, and the patient was treated with
betamethasone ointment twice daily for 4 weeks with no
improvement. We did not find any regression of the lesion
after biopsy. Because the lesions were asymptomatic and
caused no anxiety to the patient, topical medication was
discontinued.
Granuloma annulare is a benign, self-limited condition;
the cause is unknown and the pathogenesis is poorly un-
derstood. There are several clinical variants of granuloma
annulare: localized, generalized, subcutaneous, perfora-
ting, linear, and patch types. There is an overlap between
variants, and more than one morphological type may exist
in the same patient. This patient had a rare, recently de-
scribed granuloma annular variant named patch granulo-
ma annulare [1]. It appears as asymptomatic erythema-
tous to brown patches, with or without minimal scale,
that may have an annular configuration on the trunk or
proximal extremities. There is no evidence of papules,
scales, or induration [2]. As with other forms of granulo-
ma annulare, there is a female predominance. There is
also a possible association with drug reaction (which
may have been present in our patient) [1-3].
A high index of suspicion is necessary to make the diag-
nosis. The differential diagnosis of patch-type granuloma
annulare includes morphea, erythema annulare centrifu-
gum, and parapsoriasis. Pathologically, this entity is cha-
racterized by an interstitial pattern of mononuclear cellular
infiltration with scattered histiocytes between collagen fi-
bers; there is mucin deposition between collagen bundles
that can be highlighted by Alcian blue and colloidal iron
stains [4]. Necrobiotic areas are usually absent. In cases
related to drug reactions, eosinophils and some lichenoid
changes at the dermal-epidermal interface are present.
Histological differential diagnosis includes necrobiosis li-
poidica and interstitial granulomatous dermatitis. Syste-
mic therapy is unnecessary because of the relatively limi-
ted involvement and asymptomatic nature of the lesions.
It is reported that patch granuloma annulare will respond
to the same therapy as other types of granuloma annulare:
cryotherapy, topical and intralesional corticosteroids for
A
DC
B
Figure 1. A) One oval lesion on the lateral portion of the
right thigh. B) Three oval violaceous patches on the posterior
left thigh. C-D) Superficial and mid-dermal interstitial infil-
trate of lymphocytes and histiocytes; there is mucin deposi-
tion between collagen bundles. HE × 50 (C), HE× 100 (D).
EJD, vol. 19, n° 3, May-June 2009 285
localized disease, and photochemotherapy, isotretinoin,
dapsone, or antimalarials for generalized disease. Resolu-
tion of patch-type granuloma annulare after biopsy has
been reported [5].
In conclusion, we present a rare and recently described
variant of granuloma annulare characterized by patches
of erythema on the extremities and trunk that lack the
usual clinical findings but display the classic histopatho-
logical findings of interstitial granuloma annulare.
■
Acknowledgements. Financial support: none. Conflict of
interest: none.
1
Dermatology Department, Hospital
de Faro
2
Dermatology Department, Hospital
de Curry Cabral
3
Pathology Department, Hospital
de Curry Cabral
<ricardolaocoelho@yahoo.com>
Ricardo COELHO
1
Rodrigo C ARVALHO
2
Ana R ODRI GUES
2
Ana AFONSO
3
Jorge CARDOSO
2
1. Mutasim DF, Bridges AG. Patch granuloma annulare: clinicopatho-
logic study of 6 patients. J Am Acad Dermatol 2000; 42: 417-21.
2.Sa
`
bat M, Bielsa I, Ribera M, Mangas C, Ferna
´
ndez-Chico N, Fer-
ra
´
ndiz C. Granuloma anular macular. Estudio de cinco casos. Actas
Dermosifiliogr 2003; 94: 524-7.
3. Font M, Botargues N, Bonilla X, Vila
´
P. Granuloma anulare macu-
loso. Siete nuevos casos. Med Cutan Iber Lat Am 2004; 32: 23-6.
4. Victor F, Mengden S. Granuloma annulare, patch type. Dermatol
online J 2008; 14: 21.
5. Levin NA, Patterson JW, Yao LL, Wilson B. Resolution of patch-type
granuloma annulare lesions after biopsy. J Am Acad Dermatol 2002;
46: 426-9.
doi:10.1684/ejd.2009.0656
A missense mutation in exon 1 of
the keratin 9 gene in a Japanese patient
with “Vörner type ” hereditary
palmoplantar keratoderma
Epidermolytic hereditary palmoplantar keratoderma
(EHPPK; OMIM: 144200) or Vörner type PPK is charac-
terized by hyperkeratotic lesions confined to the palms
and soles, histological granular degeneration and muta-
tions in keratin 9 gene (KRT9; NCBI: NM000226) [1-5].
Here, we report a Japanese patient with EHPPK showing
a missense mutation (R162Q) in KRT9 located in the 1A
rod domain, the highly conserved helix initiation motif of
keratin 9.
A 28-year-old Japanese man was referred to us for evalu-
ation of palmar and plantar hyperkeratotic lesions. The
condition had developed within the first year of life and
progressed until 20 years of age. He sometimes shaved
the hyperkeratotic surface of the soles, but the cornified
lesion recovered within a few weeks. On examination,
there was a markedly thick cornified layer on the soles
and palms (figures 1A,B). The dorsal aspects of the
hands and feet were not affected, and the borderline
between the lesional and normal skin was clear. Hyperhi-
drosis was unremarkable. The patient was otherwise
healthy. His one-year-old daughter had the same hyper-
keratotic lesions on the bilateral palms and soles, but to
a lesser degree. The family history was otherwise negative
for similar disorders as his parents had no palmoplantar
hyperkeratosis.
A skin biopsy specimen was taken from the inner aspect
of his right foot. There was epidermolytic hyperkeratosis
exhibiting coarse keratohyaline granules and granular
degeneration (figure 1C). Thus, we diagnosed the patient
as having EHPPK.
Genomic DNA was extracted from peripheral blood
leukocytes. As previously reported [6], the genomic
regions of the KRT9 gene exon1 were amplified via poly-
merase chain reaction (PCR), using a forward : K9.E1F :
5’-GGAGGTGACTCTGCTCTTGG-3’ and a reverse:
K9.E1R : 5’-AGGTGGATTCCCTGGCTATT-3’ primer
pair. A direct sequencing analysis identified a G to
A transversion at nucleotide (nt) position 551, resulting
in the substitution of glutamine (Q) for arginine (R), in
the patient, as compared with the normal sequence
(figure 1D).
The R162Q missense mutation identified in our case was
not novel, since the mutation was located within codon
R162, in which the most common mutations, R162W
and R162P, have been reported. However this is the sec-
ond report of the R162Q missense mutation in Japanese
patients with EHPPK. This mutation has frequently been
seen in non-Japanese patients, as approximately 20%
Western cases had this mutation [1-3]. The result confirms
the previous reports of KRT9 mutation underlying EHPPK
and re-emphasizes the importance of codon R162 for
maintenance of the intermediate keratin filament network.
Since keratin 9 is confirmed to the volar skin, the abnor-
mality of keratin 9 induces palmoplantar lesions. This
dominant-negative effect on keratin network formation
led to the disruption of keratin filament formation, and
development of epidermolytic hyperkeratosis [4].
■
Acknowledgments. Financial support: none. Conflict of
interest: none.
A
B
DC
Normal
A
ATTCTCGGCTGGCCTCTT
A
ATTCTCG
A
R162Q
Patient
(Heterozygous)
GCTGGCCTCTT
Figure 1. A, B) Clinical appearance. Bilateral palmoplantar
hyperkeratotic lesions on the palms and soles. C) Histological
findings (hematoxylin-eosin, original magnification × 20).
The epidermis of the hyperkeratotic lesional skin shows epi-
dermolytic hyperkeratosis with coarse keratohyaline granules.
D) Sequence analysis of KRT9 gene exon1. Sequencing of the
Vörner type EHPPK patient’s PCR products demonstrates
heterozygous G to A substitution at nt position 551, resulting
in substitution of an arginine codon (CGG) by a codon for
glutamine (CAG), a mutation designated R162Q.
286 EJD, vol. 19, n° 3, May-June 2009
