Article

A Case of Chronic Cutaneous Graft Versus Host Disease with the Clinical Features of Exfoliative Dermatitis

Department of Dermatology, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Annals of Dermatology (Impact Factor: 1.39). 08/2009; 21(3):319-22. DOI: 10.5021/ad.2009.21.3.319
Source: PubMed

ABSTRACT

Graft versus host disease (GVHD) has traditionally been divided into acute GVHD and chronic GVHD based on the period it occurs after transplantation. Chronic cutaneous GVHD has traditionally been classified into the lichenoid and scleroderma-like forms. However, unusual clinical forms have been reported such as dermatomyositis, lupus erythematosus and exfoliative dermatitis. A 35-year-old woman presented with a 2 week history of a pruritic maculopapular rash on the whole body. The rash rapidly progressed to confluent erythematous scaly patches and plaques with micaceous scales and this finally led to a generalized exfoliative dermatitis in a 1 month period. Here we present an unusual case of chronic cutaneous GVHD with the clinical features of exfoliative dermatitis. The histopathologic examination demonstrated the lichenoid features of chronic cutaneous GVHD.

Full-text

Available from: Hyun Jeong Park, Aug 14, 2014
Vol. 21, No. 3, 2009 319
Received October 9, 2008, Accepted for publication March 5, 2009
Reprint request to: Hyun Jeong Park, M.D., Department of Derma-
tology, St. Mary's Hospital, College of Medicine, The Catholic Uni-
versity of Korea, 62, Yeouido-dong, Yeongdeungpo-gu, Seoul 150-
713, Korea. Tel: 82-2-3779-1230, Fax: 82-2-783-7604, E-mail:
hjpark@catholic.ac.kr
Ann Dermatol Vol. 21, No. 3, 2009
CASE REPORT
Fig. 1. Disseminated maculopapular exanthema on the uppe
r
extremities.
A Case of Chronic Cutaneous Graft Versus Host Disease
with the Clinical Features of Exfoliative Dermatitis
Hyo Sang Ahn, M.D., Hyun Jeong Park, M.D., Jun Young Lee, M.D., Baik Kee Cho, M.D.
Department of Dermatology, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Graft versus host disease (GVHD) has traditionally been
divided into acute GVHD and chronic GVHD based on the
period it occurs after transplantation. Chronic cutaneous
GVHD has traditionally been classified into the lichenoid
and scleroderma-like forms. However, unusual clinical
forms have been reported such as dermatomyositis, lupus
erythematosus and exfoliative dermatitis. A 35-year-old
woman presented with a 2 week history of a pruritic
maculopapular rash on the whole body. The rash rapidly
progressed to confluent erythematous scaly patches and
plaques with micaceous scales and this finally led to a
generalized exfoliative dermatitis in a 1 month period. Here
we present an unusual case of chronic cutaneous GVHD
with the clinical features of exfoliative dermatitis. The
histopathologic examination demonstrated the lichenoid
features of chronic cutaneous GVHD. (Ann Dermatol 21(3)
319322, 2009)
-Keywords-
Chronic graft versus host disease, Exfoliative dermatitis
INTRODUCTION
Graft versus host disease (GVHD) is a frequent complica-
tion that occurs in 23% to 80% of the patients who
undergo allogenic bone marrow transplantation
1
. GVHD
has traditionally been divided into acute GVHD and
chronic GVHD based on the time period it occurs after
transplantation
2
. Chronic cutaneous GVHD has traditionally
been classified into the lichenoid and scleroderma-like
forms
3
. As the incidence of GVHD has recently increased
and new, less intensive preparative regimens have been
developed, chronic cutaneous GVHD is now appearing in
pleomorphic and unusual clinical forms such as derma-
tomyositis, lupus erythematosus and exfoliative derma-
titis
4-6
. We report here on a patient who developed
chronic cutaneous GVHD with the clinical features of
exfoliative dermatitis.
CASE REPORT
A 35-year-old woman presented with a 4 day history of
myalgia. The initial laboratory test showed a WBC of
79,390/mm
3
and a PLT of 21,000/mm
3
. After bone
marrow biopsy, she was diagnosed with acute myeloid
leukemia in December 2006. She was treated with
induction chemotherapy and achieved a complete
Page 1
HS Ahn, et al
320 Ann Dermatol
Fig. 2. The histological findings of the lesion showed basal vacuolization, necrotic epidermal cells and lymphocytes in the dermis,
and this was all consistent with the diagnosis of acute cutaneous GVHD, grade II (H&E, A: ×100, B: ×200).
Fig. 3. Widespread, pruritic confluent
erythematous scaly patches and
plaques with micaceous scales on
the extremities.
response (CR) state. After consolidation chemotherapy,
she underwent allogenic BMT. She received GVHD
prophylaxis with cyclosporin and methotrexate. On the
day 23 after transplantation, she developed acute
cutaneous (demonstrated in a skin biopsy) and gut GVHD,
which resolved completely after a short course of
prednisone (Fig. 1, 2). The cyclosporin was gradually
tapered until suspension on day 115 after transplantation,
and then the patient developed oral mucositis and a
pruritic measle-like papulosquamous rash on the whole
body including the palms and soles.
There was no evidence of a leukemia relapse on the bone
marrow biopsy. She was treated with a mild topical
corticosteroid agent and oral agents (prednisone 10 mg
daily and antihistamines), but she showed no response.
Two weeks later, the rash had rapidly progressed to
confluent erythematous scaly patches and plaques with
micaceous scales and this finally led to a generalized
exfoliative dermatitis during a 2 month period (Fig. 3). The
laboratory tests showed high levels of AST 49 U/L and
ALT 99 U/L. No serologic evidence of reactivation or
recent infection by hepatitis viruses was found. The histo-
pathological examination revealed hypergranulosis, acan-
thosis, mild spongiosis, many dyskeratotic cells of the
epidermis and a mild perivascular inflammatory infiltrate
that was mainly composed of lymphocytes in the papillary
dermis (Fig. 4). These findings were consistent with the
diagnosis of chronic cutaneous GVHD. With the help of
topical agents (an emollient and a potent topical cortico-
steroid ointment) and immunosupressant agents (cyclo-
Page 2
A Case of Chronic Cutaneous Graft Versus Host Disease with the Clinical Features of Exfoliative Dermatitis
Vol. 21, No. 3, 2009
321
Fig. 4. The histological finding of the lesion showed hypergranulosis, acanthosis, necrotic keratinocytes, vacuolar alteration of the
basal layer and perivascular inflammatory cell infiltration with a faint band-like pattern (H&E, A: ×40, B: ×100).
sporine 200 mg and prednisone 20 mg daily), she finally
showed clinical improvement.
DISCUSSION
The erythematous rash and fine scaling on our patient
involved more than 90% of the body surface area and this
was clinically consistent with the diagnosis of exfoliative
dermatitis
7
. Exfoliative dermatitis may be caused by a
variety of underlying dermatoses, drug reactions and
malignancies such as lymphoma, leukemia and solid
tumors
7-9
.
Acute cutaneous GVHD usually presents as a pruritic or
burning erythematous eruption of the palms, soles, neck
and trunk. More severe reactions may progress to exfo-
liative dermatitis or total epidermal sloughing that resem-
bles toxic epidermal necrolysis
2
. Chronic cutaneous GVHD
has traditionally been classified into the lichenoid and
scleroderma-like forms
3
. However, the initial presentation
is sometimes subtle and a variety of less common cuta-
neous manifestations may be prevalent such as marked
xerosis, ichthyosis, morbilliform rash, psoriasiform plaques
and exfoliative dermatitis
10
.
Creamer et al.
6
anecdotally reported on cases of chronic
cutaneous GVHD with the clinical features of exfoliative
dermatitis. In their study, out of 254 patients who had
undergone allogenic hematopoietic stem cell transplan-
tations (HSCT), 10 patients developed exfoliative derma-
titis. The histopathologic examination revealed the com-
bined features of both eczema, as indicated by epidermal
spongiosis, and GVHD, as indicated by satellite cell
necrosis. Creamer et al.
6
named this cutaneous manifes-
tation as an eczematoid GVHD. In addition, Hymes et
al.
10
also suggested that exfoliative dermatitis is a clinical
variant of chronic cutaneous GVHD. On the other hand,
Cook-Norris and Weenig
11
commented on the article of
Creamer et al. that the eczematoid presentation may be
more accurately classified as a variant of acute GVHD.
When acute cutaneous GVHD is progressing unfavorably,
it can present as an exfoliative dermatitis or widespread
epidermal necrolysis
2
. Hence, the possibility of late onset
acute GVHD
12
, which develops during the period of
chronic GVHD, must be considered in our case.
However, our patient had classic exanthematous acute
GVHD earlier, and this resolved completely after a short
course of prednisone. On the day 115 after transplan-
tation, she developed a measle-like papulosquamous rash
that was different from the previous skin lesions and it was
not easily controlled with administering systemic
immunosuppressive therapy. The oral mucositis and the
high levels of liver enzymes in our case may be suggestive
of acute GVHD, but chronic GVHD is also accompanied
by oral involvement in 90% of the cases and by extra-
cutaneous involvement such as liver disease
13
. Moreover,
histopathological examination showed hypergranulosis,
acanthosis and mild spongiosis, which excluded the
possible diagnosis of acute cutaneous GVHD. Therefore,
we suggest that in our patient, the exfoliative dermatitis
Page 3
HS Ahn, et al
322 Ann Dermatol
that was observed both clinically and histopathologically
was expressed as a manifestation of chronic GVHD.
REFERENCES
1. Andrews ML, Robertson I, Weedon D. Cutaneous
manifestations of chronic graft-versus-host disease. Australas
J Dermatol 1997;38:53-62.
2. Johnson ML, Farmer ER. Graft-versus-host reactions in
dermatology. J Am Acad Dermatol 1998;38:369-392.
3. Hood AF, Soter NA, Rappeport J, Gigli I. Graft-versus-host
reaction. Cutaneous manifestations following bone marrow
transplantation. Arch Dermatol 1977;113:1087-1091.
4. Ollivier I, Wolkenstein P, Gherardi R, Wechsler J, Kuentz M,
Cosnes A, et al. Dermatomyositis-like graft-versus-host dis-
ease. Br J Dermatol 1998;138:558-559.
5. Girardi M, Herreid P, Tigelaar RE. Specific suppression of
lupus-like graft-versus-host disease using extracorporeal
photochemical attenuation of effector lymphocytes. J Invest
Dermatol 1995;104:177-182.
6. Creamer D, Martyn-Simmons CL, Osborne G, Kenyon M,
Salisbury JR, Devereux S, et al. Eczematoid graft-vs-host
disease: a novel form of chronic cutaneous graft-vs-host
disease and its response to psoralen UV-A therapy. Arch
Dermatol 2007;143:1157-1162.
7. Sehgal VN, Srivastava G, Sardana K. Erythroderma/
exfoliative dermatitis: a synopsis. Int J Dermatol 2004;43:
39-47.
8. Jih MH, Kimyai-Asadi A, Freedberg IM. Exfoliative derma-
titis. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller
AS, Leffell DJ, editors. Fitzpatrick’s dermatology in general
medicine. 7th ed. New York: McGraw-Hill, 2008:225-232.
9. Rym BM, Mourad M, Bechir Z, Dalenda E, Faika C, Iadh
AM, et al. Erythroderma in adults: a report of 80 cases. Int J
Dermatol 2005;44:731-735.
10. Hymes SR, Turner ML, Champlin RE, Couriel DR. Cutaneous
manifestations of chronic graft-versus-host disease. Biol
Blood Marrow Transplant 2006;12:1101-1113.
11. Cook-Norris RH, Weenig RH. Eczematoid graft-vs-host
disease. Arch Dermatol 2008;144:1066; author reply 1066-
1067.
12. Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney
DG, Sandmaier BM, et al. Graft-versus-host disease after
nonmyeloablative versus conventional hematopoietic stem
cell transplantation. Blood 2003;102:756-762.
13. Aractingi S, Chosidow O. Cutaneous graft-versus-host dis-
ease. Arch Dermatol 1998;134:602-612.
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