Transcript Pyoderma Gangrenosum -A review

• Pyoderma Gangrenosum
• A Review
• Abdel –Hamid M. Abdel-Aziz
• Professor of Dermatology & Venereology
• Al-Azhar University
Pyoderma Gangrenosum
Pyoderma gangrenosum
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Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis.
Clinically it starts with sterile pustules that rapidly progress and turn into painful ulcers
of variable depth and size with undermined violaceous borders. The legs are most
commonly affected but other parts of the skin and mucous membranes may also be
involved. Course can be mild or malignant, chronic or relapsing with remarkable
morbidity. In many cases PG is associated with an underlying disease, most
commonly inflammatory bowel disease, rheumatic or haematological disease and
malignancy. Diagnosis of PG is based on history of an underlying disease, typical
clinical presentation, histopathology, and exclusion of other diseases that would lead
to a similar appearance. The peak of incidence occurs between the ages of 20 to 50
years with women being more often affected than men. Aetiology has not been clearly
determined yet.
The treatment of PG is a challenge. Randomized, double-blinded prospective
multicenter trials for PG are not available. The best documented treatments are
systemic corticosteroids and ciclosporin A. Combinations of steroids with cytotoxic
drugs are used in resistant cases. The combination of steroids with sulfa drugs or
immunosuppressants has been used as steroid-sparing modalities. Anti-tumor
necrosis alpha therapy in Crohn's disease showed a rapid response of PG. Skin
transplants and the application of bioengineered skin is useful in selected cases as a
complement to the immunosuppressive treatment. Topical therapy with modern
wound dressings is useful to minimize pain and the risk of secondary infections.
Despite recent advances in therapy, the prognosis of PG remains unpredictable.
Clinical features of pyoderma gangrenosa
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Types
Pyoderma gangrenosum
There are two main types of pyoderma gangrenosum:
the 'typical' ulcerative form, which occurs in the legs
an 'atypical' form that is more superficial and occurs in
the hands and other parts of the body
Other variations are:
Peristomal pyoderma gangrenosum is 15% of all cases
of pyoderma
Bullous pyoderma gangrenosum
Pustular pyoderma gangrenosum
Vegetative pyoderma gangrenosum
Criteria for clinical diagnosis of P.G.
• Major criteria:
• 1. Rapid progression of painful necrolytic cutaneous ulcer with
irregular violaceous & undermined border.
• 2. Exclusion of other causes of cutaneous ulceration.
• Minor criteria:
• 1. History suggestive of pathergy or clijnical finding of cribriform
scarring.
• 2. Systemic disease associated with P.G.
• 3. Histological findings(sterile dermal neutrophil+ mixed
inflammation+ lymphocytic vasculitis.
• 4. Treatment response( rapid response to systemic glucocorticoid
treatment)
P.G.
The diagnosis is essentially clinical
• @P.G. is a neutrophilic dermatoses.
• @ Etio-pathogenesis is not yet well understood. P.G. is frequently
associated with auto-immune disease. Chlamydia pneumoniae is
considered as potential factor in the development & chronicity of the
disease.
• @ Histopathologic changes are not specific.
• Pyoderma gangrenosa is a destructive inflammatory disease . Its
rapid progression makes it at times a medical emergency.
• Surgery may exacerbate the lesion.
• Early diagnosis is important to prevent disfigurement
• P.G. is a non infectious neutrophilic dermatosis..
Causes
• Causes
• Though the etiology is not well understood, the disease is thought to
be due to immune system dysfunction, and particularly improper
functioning of neutrophils. In support of an immune etiology, a
variety of immune mediators such as IL-8, IL-1β, IL-6, interferon
(IFN)-γ, G-CSF, TNF, matrix metallopaptidase (MMP)-9, MMP-10,
and Elafin have all been reported to be elevated in patients with
pyoderma gangrenosum.
• Also in support of an immune etiology is the finding that at least half
of all pyoderma gangrenous patients suffer from immune-mediated
diseases. For instance, ulcerative colitis, rheumatoid arthritis,
and multiple myeloma (MM) have all been associated with
pyoderma gangrenosum. It can also be part of a syndromes such
as PAPA syndrome.
• One hallmark of pyoderma gangrenosum is pathergy, which is the
appearance of new lesions at sites of trauma
Histologic Findings
• Histologic Findings
• The histopathologic findings in pyoderma gangrenosum are not
specific. However, a biopsy is suggested in almost all instances
because it is useful in the exclusion of other diseases, such as
infections and malignancy. Microscopic features include massive
neutrophilic infiltration, hemorrhage, and necrosis of the overlying
epidermis. Histologically, this finding may simulate an abscess or
cellulitis. Neutrophils are often around and within the vessel walls,
but the full picture of vasculitis is generally absent.
• In early disease, a mixed cell infiltrate may be present. Late in the
process, granulation tissue may be present, but granuloma
formation is generally believed to be incompatible with the diagnosis
of pyoderma gangrenosum.
Low power of right anterior proximal thigh skin biopsy showing changes of pyoderma
gangrenosum. The center of the lesion (denoted by long blue arrows) shows a dense
neutrophilic infiltrate with leukocytoclasia and dermolysis (inset: high power image of
inflammatory infiltrate). Short green arrows point to undermining of epidermis by
inflammatory infiltrate to the left and cutaneous ulceration to the center and right.
Associations
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Associations
The following are conditions commonly associated with pyoderma gangrenosum:[7]
Inflammatory bowel disease:
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Arthritides:
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Myelocytic leukemia
Hairy cell leukemia
Myelofibrosis
Myeloid metaplasia
Monoclonal gammopathy
Autoinflammatory Disease:
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Rheumatoid arthritis
Seronegative arthritis
Hematological disease:
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Ulcerative colitis
Crohn's Disease
Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)
Also granulomatosis with polyangiitis
Differential diagnosis
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Differential diagnosis
Six disease categories may imitate the clinical appearance of PG :
(a) Vascular occulusive or venous disease including calciphylaxis which is particular
painful and rapidly evolving.
(b) Vasculitis. That is a particular challenge when PG develops in a patient with
vasculitic rheumatoid arthritis. Differential diagnoses of this topic include Wegener's
disease, antiphospholipid antibody syndrome, or in Adamantiades-Behcet's disease
etc.
(c) Cancer. Again the differential diagnosis is most complicated in patients with
lymphomas or leukaemia. Where the specific cutaneous lesions may present as
suppurative ulcers.
(d) Infectious disease. Ecthymata and deep [tropical] mycoses like sporotrichosis &
blastomycosis may resemble PG. The rapid onset of post-surgical PG often reminds
of acute deep skin infection such as erysipelas or gangrene . Late syphilis has
become more common again and may develop suppurative ulcerations. Deep viral
herpetic infections can resemble PG.
(e) Exogenous tissue injury. Facticious panniculitis as a part of the Münchhausen
syndrome may masquerading as PG . Insect or spider bites can cause necrotizing
skin ulcers.
(f) Drug reactions. Pustular drug reactions may masquerade as pustular PG
P.G.
Ulcerative type
Ulcerative type of P.G.
Ulcerative lesion of P.G.
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1- Site
2. Size
3. Number
4- Edge: Usually violet or blue
Ulcer edge: usually undermined & surrounding skin is erythematous
& indurated.
@ No lymphadenopathy or lymphangitis
@ On healing it leaves atrophic scar or often cribriform
@ Recurrence may occur.
@ Pain is common
Ulcer starts as small papules that break down
Cat paw appearance
Pyoderma gangrenosa
Pyoderma Gangrenosum
Deep purulent ulcerations due to pyoderma gangraenosum. In this patient later
on a lower limb amputation was necessary, since he did not response to drug
therapy.
Pyoderma gangrenosum: extensive ulcer in the anteriormedial part of the left leg, with
muscular tissue exposure, and areas of necrosis and purulent secretion; wound borders
were altered by a recent surgical intervention
Pyoderma gangrenosum. Histology showing occluded vessel (A) and necrosis
adjacent to a granuloma (B) (HE, 100x). Detail of the granuloma: showing
multinuclear giant cell, histiocytes (C) and neutrophilic abscedation (D).
Pyoderma gangrenosum, 45 days after corticosteroid therapy, azathioprine and
hyperbaric oxygen therapy: granular tissue with superficial neovascularization and
partial re-epithelization
Pyoderma gangrenosum, autologous skin graft over the wound, showing good
vascularization
Pyoderma gangrenosum: excellent final result after immunosuppression, hyperbaric
oxygen therapy and partial skin grafting
Pyoderma gangrenosa
P.G. ulcerative type
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P.G. ulcerative type :
-Violaceous border
-Overhangs over the ulcer bed
-heal with scar
Pyoderma gangrenosum
A medical condition which the body attacks itself in painful ulcers seen in
Crohn's patients. This is a picture of the lower half of the left leg.
P.G. in a case of inflammatory bowel Disease
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Pustular type of P.G.
Ecthyma-like pyoderma gangraenosum.
Erosive Pustular Dermatosis of the Arm Following Burn Injury
Confluent erosions with pustules and hyperkeratotic debris on (a) the upper
arm and (b) the forearm. (c) Close-up of pustules.
Histological appearance of biopsy from the patient’s left arm. (a) Scanning
magnification (b) Medium-power magnification. Subcorneal and intraepidermal
pustules filled with neutrophils, spongiosis at the epidermis, and diffuse dermal
inflammatory infiltrate consisting of neutrophils, lymphocytes, and erythrocytes were
noted. No sign of granuloma or vasculitis was observed.
pyoderma gangrenosa
Vesiculo-pustular type
pyoderma gangrenosa
Vesiculo-pustular type
Pustular type of P.G.
Abdominal P.G.
Bullous type of P.G.
Bullous type of pyoderma gangrenosa
patient post-initiation of steroids
Histopathology shows mixed cellular infiltrate
Penile pyoderma gangrenosum
Vegetative type of P.G.
Peristomal P. G. after ileostomy
Peristomal pyoderma gangraenosum in ulcerative colitis.
Peristomal P.G.
• Bridges of normal epithelium
may traverse the ulcer
P.G. with cribriform scar
Cribriform scaring in pyoderma gangrenosa