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Background
This disease has a more characteristic clinical appearance than a microscopic appearance. It classically presents as an erythematous pustule or nodule which progresses to become a necrotic ulcer with an undermined and violaceous edge. These ulcer may grow to be as large as 20 cm and may have satellite lesions and multiple ulcers associated with it. It tends to occur on the lower extremities, trunk, and occasionally on the head and neck. A characteristic feature is the phenomenon known as pathergy, where minor trauma initiates new lesions. This phenomenon is not unique to this disease and may be seen in other disorders such as Wegener's granulomatosis. The pathologist is called upon to exclude other conditions which PG may mimic. Most importantly, a malignancy or granulomatous process can be easily excluded by microscopic examination.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS PG AGE RANGE-MEDIAN Usually mid adult life
Childhood cases have been reported
DISEASE ASSOCIATIONS CHARACTERIZATION Systemic illness associated in 50% of cases Ulcerative colitis
Crohn's disease
Rheumatoid arthritis
Seronegative polyarthritis
Monoclonal gammopathy (usually IgA)Rare associations Chronic active and persistent hepatitis
Thyroid disease
Sarcoidosis
SLE
Hidradenitis suppurativa
Behcet's disease
Subcorneal pustular dermatosis
Isoretinoin therapy
Internal malignancies
Diabetes mellitus
Polycythemia vera
Paroxysmal noctural hemoglobinuria
Postop states
Immunocompromised states
HIV infection
Wegener's granulomatosisPULMONARY DISEASE
Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangwangmiao Rd 12, Nanjing, China.
Pyoderma gangrenosum is a rare, painful, noninfectious, ulcerative, reactive neutrophilic skin condition. It is characterized by ulcers that can spread quickly showing undermined violaceous borders. Since there is no single diagnostic test, early diagnosis is always challenging. The aggressive nature of classical pyoderma gangrenosum may become apparent only with time. Pulmonary involvement of pyoderma gangrenosum maybe underreported.
We describe a case of classical pyoderma gangrenosum in a 65-year-old man with pulmonary involvement, who presented with a painful fluctuate nodule and ulcer with mucopurulent and hemorrhagic exudates, and with a monoclonal gammopathy, IgA type. One month later the ulcer and hemoptysis all disappeared after treatment with glucocorticosteroids.
The pulmonary manifestations of pyoderma gangrenosum were also reviewed.
Department of Dermatology, Mater Misericordiae Hospital, Dublin, Ireland.
We present a case of pyoderma gangrenosum (PG) mimicking a lung carcinoma. A 52-year-old woman presented with an unremitting cough. Computed tomography revealed a cavitating lung lesion. Bronchoscopy and biopsy were interpreted as squamous cell carcinoma. Following a staging mediastinoscopy, a sleeve lobectomy and chest-wall resection was performed. The pulmonary histopathological features suggested Wegener's granulomatosis; no malignancy was found. Three months postoperatively, wound breakdown led to dermatological review. A clinical diagnosis of cutaneous PG was made on the basis of the classic appearance of the surgical wounds and an ulcer on the upper back that had been present before surgery. The patient has been consistently negative for cytoplasmic-staining antineutrophil cytoplasmic antibodies, which supports the diagnosis of PG with cutaneous and pulmonary involvement. Lung manifestations of PG are rare. PG is amenable to systemic therapy.
Pulmonary PG is a rare but important differential diagnosis that is not familiar to many physicians and surgeons in this type of presentation.SUBCORNEAL PUSTULAR DERMATOSIS
Mid-Western Regional Hospital, Dooradoyle, Limerick, Ireland.
We report a 57-year-old woman with a 12-year history of ulcerative pyoderma gangrenosum (PG). Five years after the onset of PG, she developed subcorneal pustular dermatosis (SPD) and biclonal IgA and IgG gammopathy. She developed PG at two bone-marrow biopsy sites, showing pathergy. Finally, she developed multiple myeloma.
Although PG and SPD may occur without associated underlying malignancy, these patients should be followed up for any prospective malignancy because of the association between these disorders.SWEET'S SYNDROME
- The relationship between neutrophilic dermatosis of the dorsal hands and sweet syndrome: report of 9 cases and comparison to atypical pyoderma gangrenosum.
Walling HW, Snipes CJ, Gerami P, Piette WW.
Department of Dermatology, University of Iowa, Iowa City, USA.
Arch Dermatol. 2006 Jan;142(1):57-63. Abstract quote
BACKGROUND: Neutrophilic dermatoses are a collection of diseases with varying presentation unified by clinical and histologic features. Neutrophilic dermatosis of the dorsal hands is a recently described clinical entity and an evolving disease concept. Its relationship to acute febrile neutrophilic dermatosis (Sweet syndrome), pyoderma gangrenosum, and a primary vasculitis has been debated.
OBSERVATIONS: We present 9 cases (8 women and 1 man) of neutrophilic dermatosis of the dorsal hands, all with consistent histologic features. Two cases had histologic evidence of vasculitis, and 3 had clinical extension of lesions onto the forearms. Most showed fever, leukocytosis, and/or elevated erythrocyte sedimentation rate. Individual cases were associated with leukemia, lung carcinoma, and inflammatory bowel disease. All 9 patients responded to systemic corticosteroid therapy, with additional response to dapsone, methotrexate, and potassium iodide therapies in several cases. Of the 9 patients, 5 showed complete resolution of their skin disease, whereas 4 required ongoing therapy. We assessed the 43 cases previously reported in the literature.
CONCLUSION: The clinical presentation, laboratory data, histologic features, and response to corticosteroid therapy offer strong evidence that neutrophilic dermatosis of the dorsal hands is a localized variant of Sweet syndrome and is also identical to atypical pyoderma gangrenosum when that condition presents on the hands.
PATHOGENESIS CHARACTERIZATION CLONALITY
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, NY, USA.
Background: The neutrophilic dermatoses encompass, among others, Sweet's syndrome (SS) and pyoderma gangrenosum (PG), which are associated with underlying systemic diseases including myeloid dyscrasias.
Methods: On skin biopsies from 16 patients with biopsy-proven SS and/or PG, we performed an X-inactivation assay to detect clonal restriction of neutrophils. There were two patient categories based on known diseases at the time of diagnosis: patients with myeloproliferative disease and patients without myeloproliferative disease.
Results: Among seven patients with acute myelogenous leukemia and two with myelodysplastic syndrome, clonal restriction was found in five; three were homozygous, precluding analysis. Among the seven control patients, infiltrates were clonally restricted in five; one was polyclonal and the other was homozygous for the allele, precluding analysis. Of the five patients with clonally restricted infiltrates, one was subsequently diagnosed with myelodysplasia, one had unexplained neutropenia and an additional patient developed breast cancer. Overall, the incidence of clonality in both groups was the same, averaging 81%.
Conclusion: These findings suggest that clonality in neutrophilic dermatoses, while characteristic of underlying myeloid dyscrasia, is not observed exclusively in the setting of myeloproliferative diseases. The significance of clonal neutrophilic infiltrates unassociated with myeloproliferative disease is unclear, but it may have some implications regarding the pathogenesis of sterile neutrophilic infiltrates. Clonality is well described in the setting of lymphomatoid hypersensitivity, reflecting an overzealous response to antigenic stimuli. One could speculate a similar mechanism operational in cases of apparently reactive SS/PG associated with monoclonality; a localized form of cutaneous neutrophilic dyscrasia is also possible.IMMUNE SYSTEM DEFECTS Possible defects in humoral, cell mediated, and neutrophil function Unclear if a vasculitis plays a role
CLINICAL VARIANTS CHARACTERIZATION GENERAL
Pyoderma gangrenosum: a review.Neil Crowson A, C Mihm Jr M, Magro C.
Departments of Dermatology and Pathology, University of Oklahoma and Regional Medical Laboratory, St John Medical Center, Tulsa, OK, USA; Departments of Dermatology and Pathology, Harvard Medical School, Massachusetts General Hospital, Boston, MA; and Division of Dermatopathology, Department of Pathology, Ohio State University, Columbus, OH.
J Cutan Pathol 2003 Feb;30(2):97-107 Abstract quote Since its first description in 1930, the pathogenesis of pyoderma gangrenosum (PG) has remained obscure even as an ever-widening array of systemic diseases has been described in association with it.
The histopathologic distinction of PG from other ulcerative processes with dermal neutrophilia is challenging and at times impossible. In consequence, when confronted with a biopsy from such a lesion, the pathologist has an obligation to obtain a full and detailed clinical history.
In short, as a diagnosis of PG does not hinge exclusively upon the biopsy findings in isolation from other studies, a solid knowledge of the clinical features, the systemic disease associations and the differential diagnosis will help the pathologist to avoid diagnostic pitfalls or the generation of a report which is non-contributory to patient care.
In this review, we describe in detail the different clinicopathologic forms of PG, summarize the diseases associated with this process in the literature and in our experience, and briefly review the treatment options.
PENIS
First Department of Dermatology and Venereology, University of Athens School of Medicine, “Andreas Sygros” Hospital, Kesariani, Athens, Greece.
We report the case of a 17-year-old boy who presented with penile ulceration and a urethral fistula that had failed to heal after plastic reconstructions with skin grafts. The patient had a history of pathergy, because the initial lesion was an ulcer that deteriorated and led to the development of the fistula after surgical interventions for its repair.
On the basis of the patient's history and normal laboratory evaluation findings, the diagnosis of penile pyoderma gangrenosum was made, and the patient began corticosteroids and cyclosporine. Four months after treatment initiation, the penile area was free of inflammation and ulceration.VARIANTS BULLOUS Bullae at advancing edges
Associated with hematologic malignancies
Histologically resembles Sweet's syndromeFAMILIAL Rare MALIGNANT PYODERMA Ulcerating destructive condition of the head and neck and upper trunk SUPERFICAL GRANULOMATOUS PYODERMA J Am Acad Dermatol 1988;18:511-521
Mayo Clini Proc 1989;64:37-43
Br J Dermatol 1993;129:718-722
Superficial ulcer
Solitary on trunk or upper extremities
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES BEHCET'S SYNDROME
Department of Dermatology, National Hospital Organization, Yokohama Medical Center, Kanagawa, Japan.
It is occasionally difficult to distinguish between Behcet's disease (BD) and pyoderma gangrenous (PG).
Our case showed ulcers of the oral, vaginal and perineal areas, and in the ileum, thus resulting in our initial diagnosis of BD. However, the patient showed a continued leukopenia, and she was subsequently diagnosed by bone marrow biopsy as having a myelodysplastic syndrome, which will sometimes accompany PG. In addition, following a hysterectomy, the ulcers of the stump in the vagina and the perineum showed the characteristic findings of a PG-like destructive ulceration.
Based on these findings, we finally diagnosed our case to have PG.Sweet's syndrome Bullous variant may have dermal neutrophilia, indistinguishable from Sweet's syndrome
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Lesions may either pursue an acute progressive course or chronic course with slow extension
Heal with scar
- Poor prognosis of arthritis-associated pyoderma gangrenosum.
Charles CA, Bialy TL, Falabella AF, Eaglstein WH, Kerdel FA, Kirsner RS.
Departments of Dermatology and Cutaneous Surgery and Epidemiology and Public Health, University of Miami School of Medicine, Miami, Fla.
Arch Dermatol. 2004 Jul;140(7):861-4. Abstract quote
BACKGROUND: The association between pyoderma gangrenosum (PG) and arthritis is well established. We have observed a refractory population of patients with arthritis-associated PG (PGA). We, therefore, tested the hypothesis that differences exist in response to treatment in patients with PGA compared with patients with PG without arthritis.
OBSERVATIONS: We performed a review of patients with PG during a 2-year period. Patients had noninfectious chronic ulcerations clinically typical for PG, exclusion of relevant differential diagnoses, and consistent histopathological features. Outcomes compared between patients with arthritis (PGA) and without arthritis (PG) included complete healing, percentage change in wound size, and duration of therapy. Of 10 PG ulcers, 7 healed, compared with 2 of 8 PGA ulcers. There was a greater mean percentage decrease in wound size in the PG vs the PGA ulcers (78.9% vs 23.4%; P =.10) and a shorter mean duration of treatment (8.7 vs 14.8 months; P =.18).
CONCLUSIONS: The ulcers of patients with PGA seem more refractory to treatment than the ulcers of patients with PG alone. Those with PGA ulcers represent a refractory subset of patients, and the ulcers are possibly secondary to unique pathophysiological features.TREATMENT Dapsone
Sulfapyridine
Minocycline
Tetracycline
Aggressive lesions may require steroids
GENERAL
- Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients.
Reichrath J, Bens G, Bonowitz A, Tilgen W.
Dermatology Clinic, The Saarland University Hospital, Homburg/Saar, Germany.
J Am Acad Dermatol. 2005 Aug;53(2):273-83. Abstract quote
Because the incidence of pyoderma gangrenosum (PG) is low, no prospective randomized controlled trials and only a few studies with case numbers of more than 15 patients have been published. To date no guidelines for treatment of PG have been established far. The aim of the study was to provide an evidence-based review of the literature and an evaluation of recommendations for PG treatment.
We performed an electronic search using the PubMed database and the term "pyoderma-gangrenosum." Literature published in the English language during the past two decades was reviewed. All relevant studies that could be obtained regardless of the study design were evaluated for grades of recommendation and levels of evidence. Data on patient characteristics including severity of the disease, localization of lesions, associated diseases, and treatment procedures were abstracted and evaluated for therapeutic outcome.
We conclude that therapeutic efficacy of systemic treatment with corticosteroids and cyclosporine is best documented in the literature for disseminated as well as for localized disease and should be considered first-line therapy. In cases that do not respond to this treatment, we recommend alternative therapeutic procedures (eg, systemic treatment with corticosteroids and mycophenolate mofetil; mycophenolate mofetil and cyclosporine; tacrolimus; infliximab; or plasmapheresis), considering additional factors including associated diseases.ALEFACEPT
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Background Pyoderma gangrenosum (PG) is a chronic inflammatory disease that causes painful cutaneous ulcers that are difficult to treat. Currently, systemic immunosuppressants, often including prednisone, are the mainstay of therapy. Long-term therapy with these agents is often required which exposes patients to possible adverse effects. An alternative treatment that is safe and effective is truly needed.
Objective To study the efficacy and safety of alefacept, which inhibits T-cell activation and selectively reduces the T-cell population, for treatment of PG.
Method In this prospective open-label pilot study, four patients diagnosed with PG received weekly doses of 15 mg alefacept intramuscularly for 20 weeks with 12-week treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving remission as defined by a Physician Global Assessment (PGA) of 'clear' or 'almost clear.' Secondary endpoints included proportion of patients achieving 50% improvement in PG lesion size (measured in mm) and proportion of patients achieving resolution of inflammation (an erythema score of 0 and a border thickness of 0 on scales of 0-4). Results By week 20, one (25%) of the four patients achieved remission, two showed marked improvement in severity on PGA, and one had slight improvement. One patient showed a 98% decrease in lesion size; two other patients evidenced a decrease in the number of small lesions as well as improvements in primary lesion sizes, but did not surpass the 50% criterion. All four patients showed improved erythema scores during treatment, though only one patient showed a complete resolution of inflammation.
Limitations It may be difficult to generalize the results of this study to a larger population of patients with PG due to the small sample size and lack of a control group. A longer treatment interval might have been required. Safety and efficacy of long-term therapy is unknown.
Conclusion In this pilot study it appears that alefacept treatment may significantly reduce PG severity levels as evidenced by improvement in PGA, Subject Global Assessment, and inflammation scores in all patients. Alefacept may be a safe and effective alternative to current systemic immunosuppressants used to treat PG. Double-blinded, controlled trials are necessary to further evaluate the safety and effectiveness of this treatment.ETANERCEPT
Department of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, UK.
Pyoderma gangrenosum (PG) is a rare and painful skin condition of uncertain aetiology characterised by one or more areas of chronic ulceration with well demarcated and undermined borders. The exact pathogenesis of PG is poorly understood but an abnormality in the regulation of the immune system or its effectors is suspected. Pathergy (the development of lesions in areas of trauma) may also play a role in the development of PG. This implies that PG may be the result of an uncontrolled and exaggerated/altered inflammatory response to nonspecific stimuli. Patients of any age may be affected by PG but it occurs predominantly in the fourth or fifth decades of life. Patients with PG present with recurrent and destructive ulcers which may begin as pustules and eventually resolve as crater-like scars. As there are currently no diagnostic tests for PG the diagnosis must be made by exclusion.
We now report the successful treatment of a patient with pyoderma gangrenosum, resistant to standard steroid therapy, using the anti-TNFalpha drug Etanercept. We believe that this is the first such report in the plastic surgery literature.ANTI-TUMOR NECROSIS FACTOR MONOCLONAL ANTIBODY Improvement of Pyoderma Gangrenosum and Psoriasis Associated With Crohn Disease With Anti–Tumor Necrosis Factor [alpha] Monoclonal Antibody
Mei-Heng Tan, MD; Marsha Gordon, MD; Oscar Lebwohl, MD; James George, MD; Mark G. Lebwohl, MD
Arch Dermatol. 2001;137:930-933 Abstract quote
Background Infliximab is an anti–tumor necrosis factor [alpha] monoclonal antibody IgG effective in the treatment and maintenance of remission of active refractory Crohn disease and associated draining enterocutaneous fistulae. Multiple infusions of infliximab show promising results in patients with rheumatoid arthritis. Currently, there is limited clinical experience with infliximab, and no published reports exist on its use in cutaneous disorders.
Observations We describe 2 patients with Crohn disease and pyoderma gangrenosum and 1 patient with Crohn disease and psoriasis who were treated with infliximab for recalcitrant Crohn fistulae, with concurrent improvement in their skin diseases.
Conclusions These cases suggest that infliximab, a promising therapeutic agent for refractory Crohn disease and fistulae, may also be effective in the treatment of pyoderma gangrenosum and psoriasis associated with Crohn disease.
IMMUNOGLOBULIN, INTRAVENOUS
Superficial granulomatous pyoderma treated with intravenous immunoglobulin.Dobson CM, Parslew RA, Evans S.
Department of Dermatology, Royal Liverpool University Hospital, United Kingdom.
J Am Acad Dermatol 2003 Mar;48(3):456-60 Abstract quote Superficial granulomatous pyoderma is a rare variant of pyoderma gangrenosum. The superficial ulceration and vegetative margins are clinically distinctive; the suppurative and granulomatous histology is characteristic, though not pathognomonic.
The condition is said to be relatively benign and more responsive to treatment than classic pyoderma gangrenosum, though published evidence of this is not always convincing.
We present a case of superficial granulomatous pyoderma that was unusually aggressive, but that underwent dramatic and lasting resolution after intravenous immunoglobulin therapy.
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