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Pyoderma gangrenosum in association with undifferentiated seronegative spondylarthropathy.

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Val. 39, No. 6, June 1996, pp 1062-1065
0 1995, American College of Rheumatology
The cases of 2 women with pyoderma gangrenosum (PG) and undifferentiated seronegative spondylarthropathy (SPA) are described. These 2 cases, together
with the recently reported case of PG and B27-positive
psoriatic spondylarthropathy, suggest that PG may also
occur in association with forms of seronegative SPA that
are different from primary ankylosing spondylitis (AS)
and AS associated with inflammatory bowel disease.
Pyoderma gangrenosum (PG) is a rare, chronic,
ulcerating, inflammatory cutaneous lesion of unknown
etiology (1-3). It starts as a painful nodule or sterile
pustule that breaks down to form a progressively enlarging ulcer with a necrotic base and raised, rugged, violaceous, undermined edges, surrounded by a peripheral
zone of intense erythema. The lesions may be solitary or
multiple and may develop anywhere, but are most
frequently located on the legs. Often, they develop at
sites of skin injury (pathergic phenomenon). Despite
distinctive clinical features, the histopathology is not
PG has been found in association with systemic
diseases, including inflammatory bowel diseases (IBD),
a variety of hematologic disorders, and arthritis (1-3).
Both rheumatoid arthritis and ankylosing spondylitis
(AS) have been reported in patients who have PG, with
or without IBD (1-4). Recently, Smith and White
reported the case of a B27-positive man with PG and
psoriatic arthritis, which suggests that PG may also occur
Supported in part by a research grant from the AISpA
(Associazione Italiana Spondiloktrite).
Ignazio Olivieri, MD, Angela Maria Costa, MD, Raffaela
Marini, MD, Silvio Ferri, MD: S. Orsola-Malpighi Hospital, University
of Bologna, Bologna, Italy; Fabrizio Cantini, MD, Laura Niccoli, MD:
Hospital of Prato, Prato, Italy.
Address reprint requests to Ignazio Olivieri, MD, Servizio di
Reumatologia, Policlinico S. Orsola-Malpighi, Via Massarenti 9, Bologna 40138, Italy.
Submitted for publication April 27, 1995; accepted in revised
form February 12, 1996.
in association with other forms of seronegative spondylarthropathy (SPA) (5). We describe here the cases of 2
B27-positive women with PG and undifferentiated SPA.
Patient 1. The patient, a 66-year-old woman, was
referred to the Rheumatic Disease Unit of Prato Hospital in July 1990 for evaluation of arthritis of the left
wrist and metacarpophalangeal (MCP) joints, which had
begun 2 months before.
Her medical history revealed that she had had a
painful, large, skin ulcer of her right leg for 35 years that
was attributed to venous insufficiency. The lesion did not
respond to various topical treatments, including fullthickness skin grafting. In the previous 10 years, she had
experienced short episodes of mechanical low back pain.
Her family history revealed that her son had
ulcerative colitis and that a sister living in a different city
had been diagnosed as having a rheumatic inflammatory
Physical examination showed soft tissue swelling,
tenderness, and warmth of the left wrist and MCP joints.
Spine movement and chest expansion were normal. On
the distal part of her left lower leg, there was a large
cutaneous ulceration that extended almost the entire
circumference. The base of the ulcer was covered with
necrotic material and purulent exudate, and was studded
with multiple small abscesses. Its border was elevated,
edematous, 3 mm wide, violaceous, and undermined.
Laboratory evaluation revealed an erythrocyte
sedimentation rate (ESR; Westergren) of 66 mm/hour, a
C-reactive protein level of 48 mg/liter (normal <5), and
a fibrinogen level of 6.58 gm/liter (normal 2-4). Results
of tests for rheumatoid factor and antinuclear antibodies
were negative. HLA typing showed A24,A25;B8,B27;
C W ~ , C W ~ ; D R ~ , D R W ~ ~ ;antigens.
Hand radiographs showed only soft tissue swelling. Spine radiographic findings were normal, and an
Figure 1. Biopsy specimen from the undermined edge of the lesion
from patient 1, showing a nonspecific mixed inflammatory cell infiltrate.
anteroposterior view of her pelvis showed bilateral grade
2 sacroiliitis.
Skin biopsy revealed findings consistent with the
diagnosis of PG: necrosis of the dermis, massive cellular
infiltrates, mainly neutrophils (Figure I), and fibrinoid
necrosis of the vessel walls.
The patient was given indomethacin at a dosage
of 100 mglday and 20 mg of methylprednisolone daily.
The wrist was injected with triamcinolone hexacetonide.
The dosage of methylprednisolone was gradually tapered to 6 mglday. One month later, the arthritis had
subsided, and considerable healing of the PG was observed. Azathioprine (2 mglkglday) was then added to
the drug regimen. Both systemic corticosteroids and
cytotoxic agents are part of the standard therapy of PG.
Over the following 10 months of therapy, the PG
healed completely, leaving an atrophic and cribriform
scar. The PG has not reappeared so far. As late as March
1996, the patient has not developed symptoms suggestive
of IBD.
Patient 2. The patient, a 32-year-old woman, was
admitted to the Institute of Dermatology of the University of Bologna in June 1993, for evaluation of multiple
ulcerative skin lesions which had appeared 5 months
Her medical history revealed that at the beginning of the skin disease, she had also had arthritis of her
left ankle for about 1 month, which was diagnosed by her
general practitioner. At the age of 29, she had lumbar
spine surgery for persistent low back pain. In the 6 years
before the present admission, she had experienced numerous episodes of symptomatic intermittent Mobitz
type I1 second-degree atrioventricular block.
Her family history was negative for IBD and SPA.
Physical examination revealed multiple ulcerative
lesions 2-6 cm in diameter (Figure 2) on the trunk,
abdomen, and upper and lower extremities. One lesion
developed on the scarred area over the lumbar spine.
Most of the lesions began as a sterile abscess that broke
down to form a superficial, slowly progressive ulcer with
vegetative border. There was tenderness over the calcaneal insertion of both plantar aponeuroses, both Achilles tendons, the adductor muscles of the right thigh, and
the levator muscles of the right scapula. Spine movement and chest expansion were normal.
The only aspect of the laboratory results worth
noting was an ESR of 40 mm/hour. Tests for antinuclear
antibodies and the rheumatoid factor were negative.
HLA typing showed Al,A28;B17,B27;DRwl1(5),DRw8;
DQw3,DQw4 antigens.
Multiple cutaneous biopsy specimens demonstrated a diffuse, nonspecific, chronic inflammation.
Spine, sacroiliac joint, and foot radiographs showed
normal results. Two-dimensional echocardiography and
continuous 24-hour ambulatory electrocardiography results were negative.
The patient was given clofazimine at a dosage of
200 mglday and diclofenac at a dosage of 100 mglday.
In October 1993, she experienced persistent,
steady abdominal pain localized to the lower quadrants
and was again admitted to the hospital. Results of
air-contrast barium enema and small bowel radiography,
fiberoptic colonoscopy, and ileal and colonic biopsy were
negative. Due to the worsening of the PG, clofazimine
was discontinued and cyclosporine (3 mglkglday) was
begun. After about 30 days, the abdominal pain subsided. In November 1993, the patient had a gynecologic
intervention for what was considered to be the cause of
the pain referred to the abdomen. In the following
Figure 2. Disseminated lesions of pyoderma gangrenosum affecting
the abdomen in patient 2.
Figure 3. A pyoderma gangrenosum lesion developed where a catheter had been inserted in the external jugular of patient 2.
weeks, a PG lesion developed on the skin of her neck
where a catheter had been inserted into the external
jugular (Figure 3).
During the first months of 1994, the daily dose of
cyclosporine was increased, first to 4 mg/kg/day and then
to 5 mg/kg/day, which was successful in producing considerable improvement of the skin lesions. During 1994,
the patient continued to experience symptomatic Mobitz
type I1 second-degree atrioventricular block, peripheral
enthesopathy, and inflammatory low back pain, which
did not respond to nonsteroidal antiinflammatory drugs.
Findings of spine and sacroiliac joint radiographs performed in November 1994 were normal.
The 2 patients presented here were unquestionably affected by SPA. Both were B27-positive and
showed typical clinical and radiographic features of SPA.
Both met the Amor (6) and the European Spondylarthropathy Study Group (7) classification criteria. Patient l developed a self-limiting peripheral arthritis and
showed a bilateral grade 2 sacroiliitis. Patient 2 developed arthritis of the left ankle, enthesitis of the heel, the
adductor longus, and the levator scapulae muscles, inflammatory low back pain, and a B27-associated atrioventricular block. Both patients cannot be classified into
any of the definite clinical entities of the SPA complex
and can be considered to have undifferentiated seronegative SPA.
The clinical spectrum of SPA has been broadened
in the last few years. In addition to AS, psoriatic
arthritis. Reiter’s syndrome, reactive arthritis, and SPA
associated with IBD, there are forms that fail to meet
any of these criteria and are designated as undifferentiated SPA (7-10). Their clinical spectrum is wide, resulting from the various combinations of the clinical and
radiologic manifestations of SPA, such as peripheral
arthritis, dactylitis, peripheral enthesitis, chest wall pain,
inflammatory spinal pain, aortic regurgitation with conduction defects, sacroiliitis, uveitis, and conjunctivitis,
each of which may also occur alone (6-15). The frequency of undifferentiated SPA is not exactly known
because, due to the lack of classification criteria, they
have been excluded by most epidemiologic studies performed in the past. Some recent studies suggest that
their frequency is higher than that of AS and that of
Reiter’s syndrome (16-18). According tQ Zeidler et al,
undifferentiated SPA is not a subtype or a new distinct
entity of the SpA complex, but rather a provisional
diagnosis for differentiating such patients from those
with other rheumatic inflammatory diseases. According
to those authors, undifferentiated SPA includes the early
stages of definite disorders of SPA, abortive forms
(fruste forms) of SPA not developing into any traditionally accepted entities, overlap syndromes combining
features of more than one disease, and etiologically
unknown entities of SPA that may be differentiated in
the future (9). Recently, classification criteria have been
proposed for the entire group of SPA including undifferentiated SPA (6,7).
Arthritis is one of the diseases most frequently
associated with PG (1-3). It is more frequent in patients
with coexisting IBD (1). In these patients, 3 forms of
arthritis have been described (1-3). The first is “entheropathic arthritis,” characterized by asymmetric involvement of a few peripheral joints, usually the large joints of
the lower limbs, short duration, a nondestructive and
self-limiting course, and close temporal association with
flares of IBD. The second is an inflammatory disease
indistinguishable from uncomplicated AS. The third is a
seropositive or seronegative symmetric, erosive polyarthritis resembling RA. The same 3 types of arthritis
have also been described in patients with PG without gut
involvement (1-4). Recently, Smith and White have
reported the case of a man with PG and a B27-positive
psoriatic spondylarthropathy, which suggests that P G
may also occur in association with forms of SpA that
are different from both primary AS and SPA associ-
ated with IBD ( 5 ) . Our two cases of coexisting PG and
undifferentiated seronegative SPA support this hypothesis. It is possible that some of the reported cases
of PG and peripheral arthritis without IBD had
undifferentiated seronegative SPA. Our report suggests that the full spectrum of SPA must be kept in
mind when assessing patients with PG for associated
rheumatic inflammatory diseases.
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spondylarthropathy, associations, seronegative, pyoderma, gangrenosum, undifferentiated
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