ARTICLE
Auteur(s) : Margarete Niebuhr, Bernward
Völker, Alexander Kapp, Bettina Wedi
Department of Dermatology and Allergology, Hannover Medical
University, Ricklinger Str. 5, D-30449 Hannover, Germany
accepté le 5 Septembre 2006
A woman of Greek ancestry, born in 1950, was seen in our inpatient
department in November 2004 for the evaluation of subcutaneous
nodules which appeared on the lower legs, accompanied with fever
and arthralgia. Her medical history was significant for a HLA-B27
negative spondarthritis and normochrome normocyte anemia. In
January 2002 she had been admitted to the Department of
Rheumatology of another hospital with similar complaints. Thorough
investigations had led to the diagnosis of erythema nodosum after
cystitis with Enterococcus faecalis. After antibiotic treatment her
symptoms had resolved slowly.Further interviewing revealed that she
had had 3-4 of these above described episodes per year for many
years and that the appearance of subcutaneous nodules on her legs
was always secondary to cystitis. The last cystitis with
enterobacter, treated successfully with antibiotics, had been three
weeks prior to admission to our Department.Clinical examination
revealed a reduced general status with fever up to 38.5 °C.
Between 5 and 10 nodules were present on her lower legs ( (figure 1) ). They
were red, inflammatory, tender, painful and subcutaneous on
palpation, each nodule tended to last about two weeks and resolved
with residual pigmentation. The rest of her clinical examination
was normal; no other cutaneous abnormality or lymphadenopathy was
found. Lung and heart examination and palpation of liver and spleen
were normal; there were no neurologic symptoms and no superficial
bleeding.A skin biopsy was performed. The specimen showed a lobular
neutrophilic infiltrate with fat necrosis, histiocytes and
epitheloid cells (figures 3 and 4). There was no vasculitis
and no significant dermal involvement. Stains and cultures for
bacteria and fungi were negative. The histologic picture led to the
diagnosis of neutrophilic panniculitis.Laboratory investigations
revealed leucocytosis, 13 × 103/mm3 with 79%
neutrophils and 20% lymphocytes in the differential count; 11.5 g%
haemoglobin as indicator for the previous known anemia and a
20-fold increase in C-reactive protein. Bacterial urine culture was
sterile. Liver and kidney enzymes, alkaline phosphatase, amylase,
lipase, alpha-1 antitrypsin and serology for streptococci,
staphylococci, hepatitis B and C were normal. Cryoglobulin,
Cryofibrinogen, antinuclear antibodies and rheumatoid factor were
negative. Electrophoresis of serum proteins showed no increase in
immune globulins or monoclonal abnormalities. For further
investigations a chest x-ray and an abdominal and lymph node
ultrasound scan were performed. The abdominal ultrasound scan
showed spleen tumors of an unknown nature which could not been
characterized even by additional CT-scan. We transferred her to the
Department of Internal medicine where thorough investigations led
to the diagnosis of old spleen ischemia and excluded neoplasia and
hematologic malignancies. Myelogram was normal.The final diagnosis
was NP associated with bacterial cystitis.The nodules were painful
and required effective therapy. Initially, our patient received a
nonsteroidal anti-inflammatory treatment with diclofenac. She
experienced a slight improvement with less pain, but found this
improvement dissatisfying. She then received oral
methylprednisolone (60 mg per day) and improved within three days (
(figure 2) ).A
few months later she was seen in our inpatient Department again
with similar subcutaneous nodules on the lower legs. The patient
told us about having had cystitis a few weeks previously, which had
been treated with antibiotics. An abdominal ultrasound scan showed
that the spleen changes had disappeared meanwhile. Again treatment
with methylprednisolone (initially 40 mg per day with gradual
reduction) for 7 days resolved the symptoms. She was recommended to
consult a specialist for further investigations, e.g. cystoscopy,
to exclude a functional abnormality and to take methylprednisolone
as stand-by-medication secondary to the next episode of
successfully treated bacterial cystitis to prevent the eruption of
NP.
Discussion
As described previously, NP is an inflammatory disorder of the
subcutaneous fat. The diagnosis and proper classification of
panniculitis relies on histologic features, mainly the location of
the subcutaneous inflammation (septal, lobular, mixed or vascular).
In contrast to erythema nodosum, where the inflammation
predominates in the fat septa, it is localized in the fat lobules
[1].
However, NP is not a well-known condition. Women seem to be more
frequently affected than men. The painful nodules appear
predominantly on the legs. Patients always have general symptoms
such as fever, sometimes additionally pain and arthralgia. A
significant association of NP with myelodysplasia has been
described [1-3].
Sutra-Loubet et al. found five positive diagnostic criteria in
all or almost all reported cases [1]:
- 1. the elementary lesion is a nodule or plaque
- 2. general symptoms as fever, arthralgia and malaise are
present
- 3. histology shows a lobular infiltrate of
neutrophils
- 4. disease is associated with myelodysplasia
- 5. disease is highly sensitive to oral steroids
Additionally Sutra-Soubet described three negative criteria
[1]:
- 1. neutrophilic infiltrate does not predominate in the
septa
- 2. there is no vasculitis
- 3. no other known cause of panniculitis
We report a 54-year-old woman presenting with recurrent NP
secondary to several episodes of bacterial cystitis. Our patient
perfectly fits in the positive and negative diagnostic criteria of
NP described by Sutra-Loubet et al. as the elementary lesion was a
nodule, it was accompanied by general symptoms as fever and
arthralgia and was highly sensitive to oral steroids. However, it
was not associated with myelodysplasia as excluded by thorough
investigations, but secondary to bacterial cystitis. Tran et al.
[4] described a 42-year-old woman with seropositive rheumatoid
arthritis who presented a 2-month history of lower leg panniculitis
which histologically demonstrated the picture of NP. Also, a case
of NP has been described in two children with idiopathic
neutropenia following administration of G-CSF (granulocyte
colony-stimulating factor) [5]. It seems, that NP can be induced or
aggravated by G-CSF therapy. This implicates that an association
between NP and myelodysplasia is not strictly required when other
diagnostic criteria are fulfilled. As described in our patient, it
seems that NP can occur secondary to bacterial infections, too.
In our patient, NP was initially misdiagnosed as erythema
nodosum since a skin biopsy had not been performed. Maybe this
disease is more common than described in the literature, especially
in patients with M. Crohn and Colitis ulcerosa but often
misdiagnosed, as skin biopsies that would show characteristic
histologic features are not usually performed by
gastroenterologists in erythema nodosum-like skin lesions in
Crohn’s patients [6]. This hypothesis is supported by a review of
30 cases initially diagnosed as Weber-Christian panniculitis where
it was possible to make a more specific diagnosis on the basis of
pathogenesis or cause and performance of histologic examination,
e.g. erythema nodosum, phlebitis or postphlebitic syndrome and
factitial panniculitis, and therefore it was argued that the eponym
of Weber-Christian paniculitis should be abandoned [7]. As the
lesions were lobular in almost all cases and neutrophilic changes
were present in nine cases, maybe there was an undiagnosed NP,
too.
Currently it is debated whether NP is a distinct entity or a
pathologic description of specific changes in the subcutaneous fat,
especially a subcutaneous Sweet’s syndrome [8]. Rohen [8] describes
subcutaneous Sweet’s syndrome as a variant of acute febrile
neutrophilic dermatosis in which the pathologic changes are
localized within the dermis and the subcutaneous fat and the
inflammatory infiltrate can be found in either the lobules, or the
septae or both. In fact, Sweet’s syndrome should be included in the
histopathologic differential diagnosis of neutrophilic panniculitis
due to its association with myelodysplasia and high sensitivity to
oral steroids.
Sutra-Loubet et al. [1] pointed out that in Sweet’s syndrome
neutrophils invade the whole dermis, albeit that an extension to
the subcutis may be observed. They clearly differentiate NP from
Sweet’s syndrome.
However, our case demonstrating leucocytosis with increased
neutrophils in the differential count and post-infectious
occurrence in addition to highly sensitive response to oral
steroids further enhances the discussion as to whether neutrophilic
panniculitis should be considered as a new entity or as a deep
seated form of Sweet’s syndrome.
Nevertheless, our case for the first time describes an infective
aetiology of NP and thus implicates that in recurrent NP prevention
may be possible. Further reporting of cases, considering
post-infectious occurrence of the disease should establish a
correct classification.
Acknowledgements
Financial support: None. Conflict of interest: None.
References
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