Introduction
Although pyoderma gangrenosum (PG) was once considered pathognomonic of idiopathic ulcerative colitis, it
has since been described in association with a wide variety of disorders including Crohn's disease,
hematological and rheumatological conditions, hepatopathies, visceral carcinomata, and states of
immunocompromise such as human immunodeficiency (HIV) infection. The hematological disorders include acute
lymphoid and myeloid leukemia, myeloproliferative diseases (where Sweet's syndrome may co-exist with PG),
paraproteinemia, particularly of IgA class, and myeloma. Bullae may be seen in lesions associated with
myelodysplasia; myeloproliferative disease-associated cases classically prododuce an 'oystracious' scale.
The associated rheumatological diseases are rheumatoid arthritis, lupus erythematosus, seronegative
symmetrical small-joint polyarthritis and seronegative spondyloarthropathy. There are four prototypic forms
of PG : ulcerative, pustular, bullous and vegetative, only the last of which has no typical association
with underlying systemic illness. Pyoderma gangrenosum may be seen in the setting of chronic active
hepatitis, primary biliary cirhosis, and sclerosing cholangitis. A vesiculopustular variant, comprising
disseminated vesicles and necrotizing pustules, some follicular-based, has been observed in patients with
ulcerative colitis or liver disease. Ther is an overlap between the abortive pustular form of PG and a
group of sterile neutrophilic dermatoses seen in patients with underlying inflammatory bowel disease, in
patients who have gone jejunoileal bypass procedures for morbid obesity, and in patients with gastroduodenal
ulceration or Crohn's disease (ie the 'bowel dermatitis/arthritis syndrome). The acute febrile neutrophilic
dermatosis of Sweet may also be seen in these settings and likely has a similar pathophysiologic basis.
Another proptypic form of neutrophilic dermatosis, erythema elevatum diutinum, is considered by us to
represent a form of fibrosing vasculitic syndrome and can also be seen in the presence of HIV infection,
leukemia or inflammatory bowel disease.
Clinical Features
The original descriptions of PG were that of skin lesions manifesting as one or more ulcers which begin as
tender, folliculocentric pustules or fluctuant nodules with sharply circumscribed violaceous, raised edges
in which necrotic pustules may be seen. The most commonly-afflicted age group is 30-50-year olds, in whom
lesions typically affect the lower extremities and trunk. In children, buttocks, perineal region, and head
and neck area may be affected. Genitalia may be involved. A persistent and sometimes lethal ulceronecrotic
form involving the head and neck, termed malignant pyoderma, is seen in some patients who have underlying
Wegener's granulomatosis. Koebnerization occurs at sites of trauma. Roughly 50-70% of cases are associated
with systemic diseases.
Multifocal recurrent osteomyelitis and PG occuring simultaneously in a patient with ulcerative colitis has
been described. Pyoderma gangrenosum has been associated with the administration of interferon (IFN)a in
the setting of chronic granulocytic leukemia whereby discontinuation of IFN and the administration of
cyclosporin A and prednisone resulted in skin lesion resolution. Other drugs are also rarely reported to be
associated with PG, such as the antipsychotic agent sulpride.
Histopathology
Skin biopsies show a central zone of necrotizing suppurative inflammation and a peripheral "Sweet's-like"
vascular reaction defined by perivascular and intramural lymphocytic infiltrates usually without fibrinoid
necrosis.
Incipient lesions may also demonstrate papillary dermal edema and a neutrophilic interface dermatitis
mimicking dermatitis herpitiformis. Ulceration often eventuates. In some cases, a necrotizing pustular
follicular reaction may be the central nidus of tissue pathergy. The bullous variant shows epidermal
necrosis, while the superficial granulomatous variant manifests florid pseudoepitheliomatous hyperplasia
with intraepithelial and superficial dermal suppurative granulomata, plasmacytosis and prominant tissue
eosinophilia. Cases associated with Crohn's disease may exhibit granulomatous inflammation.
Differential Diagnosis
The histomorphology of an incipient lesion of pyoderma gangrenosum may closely mimic Sweet's syndrome,
although the latter is rarely folliculocentric, and clinical features often make distinction possible. As
the lesions of pyoderma gangrenosum are frequently follicular-based, the differential diagnosis should also
include other causes of necrotizing pustular follicular reactions with an accompaning vasculopathy such as
mixed cryoglobulinemia, Behcet's disease, and rheumatoid vasculitis, rare cases of eosinophilic
folliculitis, pustular drug reactions and Herpetic folliculitis. Such cases should not be misinterpreted as
bacterial folliculitis. With the exception of pustular drug reactions and eosinophilic folliculitis, these
other conditions have a necrotizing mononuclear cell or neutrophil predominant vasculitis in contrast to the
non-necrotizing mononuclear cell predominat vascular reaction seen in pyoderma gangrenosum. Other causes of
a Sweet's like vascular reaction should be considered such as the bowel-arthrosis dermatosis syndrome,
Behcet's disease, idiopathic pustular vasculitis, and Sweet's syndrome.
A vesiculopustuar eruption typically showing follicular involvement has been described in patients with
hepatobiliary disease including autoimmune hepatitis, primary biliary cirrhosis, and hepatitis C; it is felt
to closely resemble if not represent the same entity as "vesiculopustular pyoderma gangrenosum". It is
perhaps however most common in patients with ulcerative colitis. The lesions are multiple and are typically
pustular in morphology. There are two morphologies. One is characterised by superficial neutrophilic
dermolysis with subepidermal bulla formation and the other by a nonulcerating destructive suppurative
folliculitis and perifollicular neutrophilic dermolysis. Both are frequently accompanied by a neutrophilic
and lymphotic eccrine hidradermitis and a Sweet's syndrome-like vascular reaction. The perifollicular
vessels show injurious alterations which in some instances represents frank leukocytoclastic or
granulomatous vasculitis. This sterile neutrophiic folliculitis pattern can be seen in other disorders
namely collagen vascular disease especially rheumatoid arthritis, the reactive arthropathy associated
syndromes, underlying hematologic dyscrasia (IgA and IgM paraproteinemia and cutaneous T cell lymphoma).
Further corroborative evidence that sterile neutrophilic folliculitis ia a potential manfiestation of an
underlying systemic disorder is the recent description of PAPA syndrome which is the triad of pyoderma
gangrenosum, pyogeneic arthritis, and cystic acne. This pleiotropic condition is felt to be an autosomally
dominantly inherited condition.
Pathogenesis
Direct immunofluorescence testing supports a vasculopathy by virtue of perivascular deposition of
immunoreactants, mainly IgM and C3 in most patients. A humoral-based pathogenesis cannot be inferred from
this finding, as non-specific vessel injury will cause the same result; defective cell-mediated immunity
without humoral abnormalities has been implicated in some patients.
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