Eosinophilic Cellulitis (Wells’ Syndrome) in Association with Angioimmunoblastic Lymphadenopathy

Abstract

Eosinophilic cellulitis (Wells' syndrome) is an uncommon inflammatory disease with clinical polymorphism. It is often associated with infectious, allergic or myeloproliferative diseases; however, the exact aetiology is unknown. This report describes a rare case of eosinophilic cellulitis in association with angioimmunoblastic lymphadenopathy. The typical skin findings of Wells' syndrome disappeared completely following chemotherapy and autologous stem cell transplantation.

Full text

© 2007 Acta Dermato-Venereologica. ISSN 0001-5555
doi: 10.2340/00015555-0317
Acta Derm Venereol 87
CLINICAL REPORT
Acta Derm Venereol 2007; 87: 525–528
Eosinophilic cellulitis (Wells’ syndrome) is an uncommon
inammatory disease with clinical polymorphism. It is
often associated with infectious, allergic or myeloprolife-
rative diseases; however, the exact aetiology is unknown.
This report describes a rare case of eosinophilic cellulitis
in association with angioimmunoblastic lymphadenopa-
thy. The typical skin ndings of Wells‘ syndrome disap-
peared completely following chemotherapy and autolo-
gous stem cell transplantation. Key words: eosinophilic
cellulitis; Wells‘ syndrome; ame gures; T-cell lymphoma;
AILD.
(Accepted March 29, 2007.)
Acta Derm Venereol 2007; 87: 525–528.
Regina Renner, Ph.-Rosenthalstr. 23–25, DE-04103 Leipzig,
Germany. E-mail: Regina.renner@medizin.uni-leipzig.de
Eosinophilic cellulitis was rst described by Georg
Crichton Wells in 1971 under the name “recurrent
granulomatous dermatitis with eosinophilia” (1). In
1979, the name was simplified to the present term
“eosinophilic cellulitis” or Wells’ syndrome. It is an
uncommon inammatory dermatosis with suggestive
but unspecic histopathological ndings and clinical
polymorphism. It is often associated with infectious,
allergic or myeloproliferative diseases; however, the
exact aetiology is unknown. This report is the rst to
describe a case of eosinophilic cellulitis in association
with angioimmunoblastic lymphadenopathy (AILD).
CASE REPORT
Clinical and histopathological ndings
A 48-year-old man was referred to our clinic with recur-
rent oedema and swelling of the face and neck, which
had occurred during the last 3 months. In addition, he
reported generalized itching and erythema. Oral anti-
histamines had been given on suspicion of Quincke’s
oedema with chronic urticaria, but they did not control
the symptoms. He presented with inltrated erythemas
and multiple livid-erythematous papules and plaques
on the integument (Fig. 1a) including the extremities
(Fig. 1b) and the soles of his feet. There was generalized
lymphadenopathy.
Eosinophilic Cellulitis (Wells’ Syndrome) in Association with
Angioimmunoblastic Lymphadenopathy
Regina RENNER
1
, Friederike KAUER
1
, Regina TREUDLER
1
, Dietger NIEDERWIESER
2
and Jan C. SIMON
1
1
Klinik für Dermatologie, Venerologie und Allergologie, and
2
Zentrum für Innere Medizin, Medizinische Klinik und Poliklinik II, Abteilung Hämatologie
und Internistische Onkologie, Universitätsklinikum Leipzig, Germany
Fig. 1. Inltrated erythemas and multiple livid-erythematous papules and
plaques on (a) the integument and (b) the hand.

526
R. Renner et al.
Acta Derm Venereol 87
Histopathology from the skin of the thigh showed
perivascular and periadnexal as well as diffuse
eosinophilic inltration in the dermis and degenerated
basophilic collagen bres surrounded by eosinophils
and eosinophilic granules and histiocytes, the so-
called ame gures (Fig. 2). There was no evidence of
leukaemic inltration in the skin.
Lymph node biopsy revealed an inltration of a low
malignant non-Hodgkin’s lymphoma (angioimmuno-
blastic T-cell lymphoma, CD3+, CD5+, CD7-AILD).
Bone marrow puncture also showed this inltration,
in addition to a reactive increase in eosinophils. Dif-
ferential blood count showed eosinophilia of 25.5%.
Sonography of the abdomen indicated homogenous
splenomegaly. Echocardiography, chest X-ray, oto-
rhinolaryngological control, faecal occult blood test,
viral serologies (parvovirus B19, HHV 6, CMV, EBV),
Borrelia serology, and syphilis serology showed no
signicant changes.
Treatment
Therapy was initiated with dapsone 100 mg/day and
prednisolone 0.7 mg/kg with decreasing dosage, which
led to decreased inltration and erythema. When the
diagnosis of AILD was established, the therapy was
switched to chemotherapy. Meanwhile, the patient
had received multiple cycles of either vincristine,
CHOP (cyclophosphamide, doxorubicin, vincristine,
prednisolone) or ESHAP chemotherapy (etoposide,
methylprednisolone, cytarabine and cisplatin). Due to
an inadequate response of the AILD to this therapy,
autologous stem cell transplantation was carried out.
After this procedure, the typical skin ndings of Wells’
syndrome disappeared completely, leaving post-inam-
matory hypopigmentation.
DISCUSSION
Wells’ syndrome is a chronic recurring inammatory
and pruritic dermatosis of unknown pathogenesis and
aetiology. Characteristic, but not specic, are the clini-
cal ndings of erythematous-livid plaques, sometimes
oedematous or urticaria-like, that may be accompanied
by fever, myalgia and (in about 50% of all cases) ele-
vated eosinophilic cells in the blood during the active
phase of the disease (1–3). In addition, histological
ndings show so-called ame gures and further gra-
nulomatous inltration. Our patient showed typical
erythematous to urticaria-like plaques accompanied
with slight fever, elevated eosinophils in the peripheral
blood and histological typical ame gures.
Histopathological features have recently been clas-
sied into: (i) an acute stage with oedematous dermis
and dense inltration of eosinophils and histiocytes; (ii)
a subacute stage with adherent eosinophils to collagen
bres with degranulation forming the characteristic
ame gures as seen in our patient; and (iii) a resolution
stage with foreign body type giant cells, histiocytes and
few eosinophils (4).
The following diseases or trigger factors have been
described to be associated with Wells’ syndrome: insect
bites, parasites, viral infections or mycosis, immuni-
zation (5), drug eruptions, haemato-oncological diseases
or solid neoplasms (6, 7) and TNF-α-inhibitors, such as
etanercept or adalimumab (8, 9). Most haemato-oncolo-
gical diseases associated with eosinophilic cellulitis are
mantle cell lymphomas. In our case, triggering factor
might have been the additional diagnosed AILD. To our
knowledge this is the rst time that an AILD associated
with Wells’ syndrome has been reported.
A similar course of resolution of the skin lesion
following successful treatment of the haematological
disease has been described in a case of mantle-zone
lymphoma (10).
Wells’ syndrome is thought to be a hypersensitivity
reaction to divergent antigens with an eosinophilic
reaction (11). Increased interleukin-5 levels have been
observed, which mobilizes eosinophils from the bone
marrow and facilitates their homing to the skin (12–14).
Interleukin (IL)-5 also increases CD25, part of the
IL-2 receptor, which promotes degranulation of the
eosinophils. This degranulation leads to toxic damage of
the tissue and histamine release from basophils (12, 14).
Eosinophilic major basic protein (MBP) can be found
surrounding collagen bres (15); this provokes the
so-called ame gures. Vasculitis is absent, and direct
immunouorescence ndings are negative (3).
The lack of specic or unique symptoms, and an as-
sociation with different diseases, has formerly led to the
identity of Wells’ syndrome being doubted. Aberer et al.
(16) postulated it as a distinctive clinical and histological
reaction and not just an unspecic symptom of different
Fig. 2. Histopathology (H&E ×20) showed perivascular and periadnexal
as well as diffuse eosinophilic inltration in the dermis and the so-called
ame gures.

527
Wells’ syndrome with angioimmunoblastic lymphadenopathy
Acta Derm Venereol 87
diseases (17). In contrast, other authors (18) postulated
that Wells’ syndrome may be an exclusive cutaneous
manifestation of hypereosinophilic syndrome (HES).
There are, however, some factors that cast doubt on this
hypothesis. In HES, an elevated serum level of MBP can
be observed, but there is a lack of typical ame gures,
maybe because there is insufcient degranulation of
eosinophils in the skin. The pathology of skin lesion in
HES is more non-specic than in Wells’ syndrome, with
variable eosinophil inltration. In contrast, systemic
involvement or organ damage is untypical for Wells’
syndrome, but this is one important characteristic in
the denition for HES. Clinical and histopathological
ndings of both syndromes may overlap up to the fact
that cutaneous manifestations of eosinophilic cellulitis
can be part of HES (19–21).
Therapy normally relies on topical or systemic corti-
costeroids, dapsone or systemic antihistamines (2, 16,
22). In our case, the combination of systemic cortico-
steroids and dapsone seemed to be effective. It has been
described that the anti-oxidative additives of dapsone can
suppress free radicals in eosinophils (18). If a causative
agent can be identied, it may be useful to treat the un-
derlying condition (7, 10). In our case, chemotherapy
of the AILD and afterwards autologous stem cell trans-
plantation led to regression of the skin lesions.
Other therapeutic options include antimicrobial
agents (11, 16), colchicines (23), interferon-α (24),
antimalarial drugs or immunosuppressive agents,
such as cyclosporine or azathioprine (3, 25, 26). New
therapeutic options may be tyrosine kinase inhibitors,
such as imatinib. This treatment has been shown sig-
nicantly to decrease blood eosinophil cell counts in
patients who carry the FIP1L1-PDGFRA fusion gene.
This therapy was successfully carried out in a patient
with eosinophilic cellulitis in association with chronic
eosinophilic leukaemia (27).
In conclusion, depending on the clinical ndings,
Wells’ syndrome is an important differential diagnosis
to erysipelas, urticaria or drug eruption, and should be
considered in particular in patients with neoplasms and/
or elevated cell counts of eosinophilic cells in the blood
or bone marrow. It is probable that Wells’ syndrome oc-
curs more frequently than is currently assumed.
Conflict of interest: None to declare.
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