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Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis

Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis
Literature review current through: Jan 2024.
This topic last updated: Aug 10, 2022.

INTRODUCTION — Pyoderma gangrenosum (PG) is an uncommon neutrophilic dermatosis that presents as an inflammatory and ulcerative disorder of the skin. In contrast to its name, PG is neither an infectious nor gangrenous condition. The most common presentation of PG is an inflammatory papule or pustule that progresses to a painful ulcer with a violaceous undermined border and a purulent base (picture 1A-E). PG may also present with bullous, vegetative, peristomal, and extracutaneous lesions.

More than half of patients with PG develop the disorder in association with an underlying systemic disease. Inflammatory bowel disease, hematologic disorders, and arthritis represent the most frequent comorbidities.

A diagnosis of PG rests upon the recognition of consistent clinical and histologic findings and the exclusion of other inflammatory or ulcerative cutaneous disorders. There are no pathognomonic, clinical, or histologic findings of PG.

The pathogenesis, clinical manifestations, and diagnosis of PG will be discussed here. The treatment and prognosis of PG and other neutrophilic dermatoses are reviewed separately. (See "Pyoderma gangrenosum: Treatment and prognosis" and "Neutrophilic dermatoses".)

EPIDEMIOLOGY — PG is a rare disorder with an estimated incidence of 3 to 10 cases per million people per year [1]. Individuals of any age may be affected, including children [2-4]. PG most commonly develops in young and middle-aged adults, with an average age of onset between 40 and 60 years [5-8]. Between the sexes, women are more frequently affected [7].

PATHOGENESIS — Consistent with its categorization as a neutrophilic dermatosis, PG is characterized by neutrophil-predominant infiltrates in the skin. Research has begun to elucidate dysregulation in the innate and adaptive immune response, in addition to genetic factors, in the pathogenesis of PG:

Immune dysregulation – Studies have revealed complex gene expression profiles in the skin of patients with PG. Lesional skin of PG has increased expression of interleukin (IL) 1-beta, IL-1-alpha, IL-8, IL-12, IL-15, IL-17, IL-23, IL-36, and tumor necrosis factor (TNF)-alpha [9-11]. This upregulation leads to a proinflammatory state through increased activation of inflammasomes, dysregulation of the innate immune system, and recruitment and activation of neutrophils [9]. PG tissue also has increased expression of pattern recognition receptors (PRRs), JAK2, and STAT1, implicating both adaptive and innate immune response dysfunction [10]. The complement pathway, particularly C5a and its role in neutrophil activation, chemotaxis, and inflammatory signaling, may also contribute to the complex pathogenesis of PG [12].

Genetic factors – Genetic susceptibility also likely contributes to the development of PG. Familial cases of PG have been reported [13-16]. In addition, PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome (OMIM #604416), an autosomal dominant disorder, has been linked to mutations in the PSTPIP1/CD2BP1 gene. This mutation leads to decreased inhibition of the inflammasome and, ultimately, increased production of IL-1-beta and autoinflammation [17]. Mutations of the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, and LPIN2 have been demonstrated in PG, PASH (pyoderma gangrenosum, acne, and suppurative hidradenitis) syndrome, and other inflammatory conditions, including familial Mediterranean fever, cryopyrin-associated periodic syndrome, Crohn disease, and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome [9]. (See "Autoinflammatory diseases mediated by inflammasomes and related IL-1 family cytokines (inflammasomopathies)", section on 'PAPA syndrome'.)

Further elucidation of the molecular pathways in PG have allowed for more targeted treatments, including TNF-alpha, IL-1, IL-17, IL-23, and IL-6 inhibitors. (See "Pyoderma gangrenosum: Treatment and prognosis".)

CLINICAL MANIFESTATIONS — The clinical manifestations of PG are variable and can be divided into four major subtypes: ulcerative (classic) PG (the most common variant), bullous (atypical) PG, pustular PG, and vegetative PG [18].

Common features — The subtypes of PG share a clinical course characterized by the appearance of an inflammatory papule, pustule, vesicle, or nodule that subsequently expands and breaks down to form an erosion or ulcer. With the exception of vegetative PG, lesion development is often rapid and the level of pain is often greater than expected based upon the appearance of the ulcer [18]. Fever may or may not be present [19].

Pathergy, a term used to describe the induction or exacerbation of PG in sites of incidental or iatrogenic trauma, is frequently mentioned in descriptions of the clinical behavior of PG. However, not all patients with PG exhibit this feature. Data on the proportion of patients with PG who experience pathergy are limited. In a retrospective study of 103 patients with PG, pathergy was documented in the medical records of 31 percent of patients [7]. In a series of 166 patients with PG, 25 (15 percent) experienced 33 episodes of postsurgical recurrence or exacerbation of the disease; factors associated with increased risk of pathergy included open surgical procedures, Mohs surgery, and PG present at the time of procedure [20].

Subtypes — Descriptions of the major variants of PG are provided below:

Ulcerative (classic) pyoderma gangrenosum – The ulcerative variant of PG represents the vast majority of cases of PG. Ulcerative PG typically begins as a tender, inflammatory papule, pustule, or vesicle that develops on normal-appearing skin or at a site of trauma (picture 2A-B). The lower extremities and trunk are the most common sites of involvement, though lesions may occur in other areas [1].

The initial inflammatory lesion subsequently expands peripherally and degenerates centrally, leading to ulcer formation (picture 1A-E). The edge of the ulcer usually exhibits a bluish or violaceous color and demonstrates an undermined quality. Irregular expansion of the involved tissue may lead to a serpiginous configuration. The base of the ulcer is purulent and necrotic, and the depth of the ulcer often extends into subcutaneous fat and occasionally reaches the fascia [1].

Patients may have a single lesion or multiple lesions in various stages of development. Ulcers typically resolve with atrophic, cribriform scars.

Bullous (atypical) pyoderma gangrenosum – Bullous PG is a less common, superficial variant of PG that is most commonly seen in patients with PG related to hematologic disease [6]. Unlike ulcerative PG, the arms and face are the most common sites of involvement [1,6]. Patients typically present with the rapid development of blue-gray, inflammatory bullae in the involved areas [6]. The bullae quickly erode, resulting in superficial ulcers (picture 3).

Due to the strong association between bullous PG and hematologic disease, patients who present without an associated hematologic disorder should be followed closely for the development of a hematologic disorder [21].

Pustular pyoderma gangrenosum – Pustular PG usually occurs in patients with inflammatory bowel disease, and tends to arise during periods of acute exacerbations of bowel disease [18]. Affected patients exhibit the rapid development of painful pustules surrounded by erythema (picture 4). Concomitant fever and arthralgias are common [1]. Pyostomatitis vegetans, which presents with multiple small pustules and erosions on the oral mucosa, may be a variant of pustular PG [1,22].

Vegetative pyoderma gangrenosum – Vegetative PG (also known as superficial granulomatous pyoderma) is a typically localized, solitary, superficial form of PG that presents as an indolent, mildly painful nodule, plaque, or ulcer (picture 5). A verrucous quality is often present. The undermined borders and purulent bases of ulcerative PG are absent. The head, neck, and trunk are the most common sites for vegetative PG [1].

Special sites — In addition to the morphologic subtypes reviewed above, other terms have been used to describe certain presentations of PG. Examples include peristomal PG, genital PG, and extracutaneous PG:

Peristomal pyoderma gangrenosum Peristomal PG is an uncommon manifestation of PG that is characterized by the development of lesions consistent with ulcerative PG adjacent to a stoma (picture 6). This typically occurs in patients with ulcerative colitis or Crohn’s disease and may develop months to a few decades after placement of a stoma. Trauma caused by maintenance of the stoma or irritation from stoma secretions may play a role in the development of peristomal PG [1].

Genital pyoderma gangrenosum – Genital PG may involve the vulva, penis, or scrotum. Lesions resemble those of ulcerative PG (picture 7).

Extracutaneous pyoderma gangrenosum – Rarely, PG involves extracutaneous sites. In such cases, sterile neutrophilic infiltration develops in sites such as the lungs, intestine, cornea, liver, spleen, heart, bones, muscle, and central nervous system [23-35].

Postoperative pyoderma gangrenosum – Postoperative PG is the development of PG in a surgical site, usually within two weeks after surgery [36]. The initial symptoms are surgical-site erythema and extreme pain out of proportion to the physical examination followed by wound dehiscence or the development of punctate ulcerations that coalesce into larger ulcers. Postoperative PG appears to be more common in women than in men. Common sites of involvement are the breasts and abdomen [36].

ASSOCIATED DISORDERS — More than 50 percent of patients with PG have an associated systemic disease, most commonly inflammatory bowel disease, arthritis, and hematologic disease or hematologic malignancy [5-7]. The proportion of patients with specific comorbidities varies among studies [5-7,37]. In one of the largest studies, a retrospective cohort study of 356 adults with PG, 161 (45 percent) had associated comorbidities, including [37]:

146 patients (41 percent) with inflammatory bowel disease

73 patients (21 percent) with inflammatory arthritis

23 patients (7 percent) with solid organ malignant neoplasms

21 patients (6 percent) with hematologic malignant neoplasms

17 patients (5 percent) with hematologic disorders (monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, or polycythemia vera)

Additional findings of this study suggest that patient age influences risk for specific comorbidities. Patients aged 65 years or older were more likely to have associated rheumatoid arthritis, ankylosing spondylitis, solid organ malignant neoplasms, hematologic malignant neoplasms, and hematologic disorders than younger patients. Inflammatory bowel disease was more common in patients under the age of 65 years.

PG may precede or follow the diagnosis of an associated disorder and may or may not parallel the clinical course of the associated disease [21,38].

PG may occur as a feature of autoinflammatory syndromes, such as PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome, PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, and suppurative hidradenitis [hidradenitis suppurativa]) syndrome, and PASH (pyoderma gangrenosum, acne, and suppurative hidradenitis) syndrome [39-42]. PAPA syndrome is an autosomal dominant disorder and occurs secondary to a defect in the PSTPIP1/CD2BP1 gene. PAPASH syndrome has been described in an adolescent in whom a novel mutation in the PSTPIP1 gene was detected [39]. PG has also been described in a patient with dissecting cellulitis of the scalp, hidradenitis suppurativa, and inflammatory acne [43]. (See 'Pathogenesis' above and "Autoinflammatory diseases mediated by inflammasomes and related IL-1 family cytokines (inflammasomopathies)", section on 'PAPA syndrome'.)

Examples of additional disorders that have been infrequently linked to PG include pulmonary disease, systemic lupus erythematosus, thyroid disease, solid organ cancers, viral and autoimmune hepatitis, sarcoidosis, major depression, and diabetes [7,38,44]. In addition, PG has also been reported in patients exposed to levamisole [45]. Further study is necessary to validate a relationship between these disorders and PG.

DIAGNOSIS — The clinical, histopathologic, and laboratory findings in PG are nonspecific, and a diagnosis of PG can only be made once other diagnostic possibilities have been excluded. At least a clinical history, physical examination, and skin biopsy should be performed in all patients [38]. In patients known to have diseases associated with PG, the development of an ulcer should raise suspicion for this diagnosis. In addition, once PG has been diagnosed, patients should be evaluated for the presence of an associated underlying disease. (See 'Associated disorders' above and 'Laboratory studies' below.)

Diagnostic criteria — Historically, universally accepted and validated diagnostic criteria for PG have been lacking. Diagnostic criteria published in 2004 require the exclusion of all other diagnoses, which can be challenging or impractical in the clinical setting (table 1) [46]. Newer diagnostic criteria for ulcerative PG developed through a Delphi consensus of international experts provide greater structure to the diagnostic process and are our preferred tool for diagnosis [47]. These criteria include a single major criterion and eight minor criteria, including histologic, history, clinical examination, and treatment findings (algorithm 1).

Major criterion:

Biopsy of ulcer edge demonstrating a neutrophilic infiltrate

Minor criteria:

Exclusion of infection

Pathergy

Personal history of inflammatory bowel disease or inflammatory arthritis

History of papule, pustule, or vesicle that rapidly ulcerated

Peripheral erythema, undermining border, and tenderness at site of ulceration

Multiple ulcerations (at least one occurring on an anterior lower leg)

Cribriform or "wrinkled paper" scar(s) at sites of healed ulcers

Decrease in ulcer size within one month of initiating immunosuppressive medications

At least the major criterion and four minor criteria are necessary for diagnosis.

A third diagnostic criteria, the PARACELSUS score, utilizes a point system with slightly different major and minor criteria [48]. This system was designed specifically for the purpose of differentiating venous leg ulcers from PG.

Diagnostic criteria are used predominantly for clinical studies but may offer a framework for diagnosis in daily practice.

Clinical assessment — The clinical assessment of the patient with a lesion suspicious for PG should include a thorough history and physical examination. Patients should be questioned regarding the history of lesion development, associated symptoms, and personal medical history. Examples of findings attainable via a patient history that support a diagnosis of PG include:

Rapid course of lesion development

Initial lesion consistent with papule, pustule, or vesicle

Pain out of proportion to lesion

History of preceding trauma (pathergy)

History of disorders associated with PG (see 'Associated disorders' above)

The physical examination is useful for identifying the extent of disease, narrowing the differential diagnosis, and detecting clinical signs of PG-associated disorders.

Biopsy — Since the histopathologic findings of PG are nonspecific, biopsies are most useful for excluding other disorders that may present with similar clinical findings. A biopsy is indicated in patients without a preceding history of PG and in patients with established PG who present with lesions with atypical features or lesions that fail to respond as expected to therapy. Although clinicians are often concerned about biopsy-induced pathergy, the need to rule out other disorders and ensure proper treatment supersedes concern for the induction of an exacerbation of PG.

Procedure — The optimal procedure for biopsy is an elliptical incisional biopsy that incorporates both the inflamed lesion border and ulcer edge and extends vertically into the subcutaneous fat [46]. A tissue specimen that includes the inflamed border should be sent for routine histopathologic examination and microbial stains. In addition, a specimen from the ulcer should be sent for culture to evaluate for bacterial, fungal, and atypical mycobacterial infections.

Pathology — Specimens taken from the earliest lesions of PG demonstrate perifollicular inflammation and intradermal abscess formation (picture 8A-B) [49]. Once lesions progress to ulceration, epidermal and superficial dermal necrosis with an underlying mixed inflammatory cell infiltrate and abscess formation are typically detected. Giant cells may be found, and tissue from the edge of the lesion may demonstrate vascular changes suggestive of lymphocytic vasculitis. Leukocytoclastic vasculitis may also be present [49].

Additional findings may be identified based upon the subtype of PG. Specimens from bullous PG demonstrate subepidermal bullae. Pseudoepitheliomatous hyperplasia, sinus tracts, and palisading granulomas are features consistent with vegetative PG.

Direct immunofluorescence studies yield nonspecific findings in PG. Deposition of IgM, C3, and fibrin in vessel walls may be detected [38]. Because of the nonspecific nature of the results, direct immunofluorescence is usually only conducted when additional clinical findings indicate a need to exclude autoimmune bullous disease, lupus, or vasculitis as a cause of ulceration [46]. (See "Approach to the patient with cutaneous blisters", section on 'Direct immunofluorescence'.)

Laboratory studies — Similar to tissue biopsies, there are no laboratory studies that provide a definitive diagnosis of PG. Nonspecific findings such as leukocytosis, elevation of the erythrocyte sedimentation rate, and elevation of C-reactive protein levels may be present [19].

Laboratory tests are most useful for narrowing the differential diagnosis and identifying the presence of PG-associated diseases. Recommendations for the work-up of these patients vary. We typically obtain the following studies in patients with clinical and histopathologic findings consistent with PG:

Complete blood count (to evaluate for underlying hematologic disorders)

Comprehensive metabolic panel (to evaluate for hepatic or renal dysfunction and glucose abnormalities prior to initiation of systemic glucocorticoids or immunosuppressive agents)

Antinuclear antibody titer (to evaluate for the presence of systemic lupus erythematosus or collagen vascular disorders in association with PG)

Antineutrophilic cytoplasmic antibodies (to evaluate for granulomatous vasculitis as a cause of ulceration)

Hypercoagulability studies (antiphospholipid antibody screen to evaluate for antiphospholipid syndrome as a cause of ulceration; based upon clinical suspicion, other tests to evaluate for thrombotic states [eg, cryoglobulins, Factor V Leiden, methylene tetrahydrofolate reductase])

Hepatitis panel (to evaluate for associated hepatitis B or C, particularly for patients in whom immunomodulatory therapy is considered)

Rheumatoid factor (as a component of the evaluation for cryoglobulinemia and rheumatoid arthritis)

Serum immunofixation electrophoresis (to evaluate for paraproteins)

Chest radiography (to evaluate for presence of extracutaneous involvement and for possible infection prior to the initiation of immunosuppressive therapy)

Colonoscopy (to evaluate for underlying inflammatory bowel disease unless another cause of PG is identified)

Additional tests to evaluate for associated disorders and disorders in the differential diagnosis are ordered based upon clinical suspicion for specific diseases.

Differential diagnosis — Due to the lack of a definitive test for PG, misdiagnosis can occur. In one retrospective study, 15 of 157 consecutive patients seen at an academic institution and given a diagnosis of PG (10 percent) were subsequently found to have an alternative diagnosis [50].

Vascular occlusion disorders, venous disease, vasculitis, malignancy, cutaneous infection, drugs, exogenous tissue injury, and ulcerative inflammatory disorders (eg, cutaneous Crohn’s disease and ulcerative necrobiosis lipoidica) may be mistaken for PG (table 2) [50]. Antiphospholipid-antibody syndrome is one of the most common disorders mistaken for PG; other more commonly confused disorders include venous stasis ulcers, granulomatosis with polyangiitis, factitial ulcers, sporotrichosis, polyarteritis nodosa, livedoid vasculopathy, angiocentric T cell lymphoma, and cryoglobulinemia [50]. Necrotizing fasciitis is an additional potential misdiagnosis [51]. Aggressive debridement for this presumed diagnosis can lead to significant morbidity and deformity [52-54]. (See "Neutrophilic dermatoses", section on 'Necrotizing neutrophilic dermatoses' and "Necrotizing soft tissue infections".)

The clinical history, biopsy, and directed laboratory studies attained during patient evaluation aid in distinguishing PG from other diseases. Reassessment of a diagnosis of PG is indicated if the disease fails to respond as expected to therapy. (See "Pyoderma gangrenosum: Treatment and prognosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pyoderma gangrenosum".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Pyoderma gangrenosum (The Basics)")

SUMMARY AND RECOMMENDATIONS

Epidemiology – Pyoderma gangrenosum is an uncommon neutrophilic dermatosis that most commonly presents with inflammatory ulcers on the skin. Although PG may occur at any age, there is a predilection for young and middle-aged adults and women. (See 'Epidemiology' above.)

Pathogenesis – The factors that contribute to the development of PG are not well understood. Factors that are postulated to contribute to PG include dysregulation of the immune system and genetic susceptibility. (See 'Pathogenesis' above.)

Clinical manifestations – The clinical manifestations of PG vary. The most common presentation is ulcerative (classic) PG, which typically presents as a rapidly developing, painful purulent ulcer with a violaceous and undermined border (picture 1A-E). Other variants of PG include bullous, pustular, and vegetative presentations. PG may also develop in peristomal, genital, and extracutaneous locations. (See 'Clinical manifestations' above.)

Associated disorders – More than 50 percent of patients with PG have an associated systemic disease. The strongest associations are between PG and inflammatory bowel disease, hematologic disorders, and arthritis. (See 'Associated disorders' above.)

Diagnosis – Since the clinical and histologic findings of PG are nonspecific, PG is a diagnosis of exclusion (table 2). At a minimum, the patient evaluation should include a patient history, physical examination, and biopsy to detect findings consistent with PG and to rule out other diseases. (See 'Diagnosis' above.)

  1. Ruocco E, Sangiuliano S, Gravina AG, et al. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 2009; 23:1008.
  2. Allen CP, Hull J, Wilkison N, Burge SM. Pediatric pyoderma gangrenosum with splenic and pulmonary involvement. Pediatr Dermatol 2013; 30:497.
  3. Bhat RM, Shetty SS, Kamath GH. Pyoderma Gangrenosum in childhood. Int J Dermatol 2004; 43:205.
  4. Torrelo A, Colmenero I, Serrano C, et al. Pyoderma gangrenosum in an infant. Pediatr Dermatol 2006; 23:338.
  5. von den Driesch P. Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol 1997; 137:1000.
  6. Bennett ML, Jackson JM, Jorizzo JL, et al. Pyoderma gangrenosum. A comparison of typical and atypical forms with an emphasis on time to remission. Case review of 86 patients from 2 institutions. Medicine (Baltimore) 2000; 79:37.
  7. Binus AM, Qureshi AA, Li VW, Winterfield LS. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients. Br J Dermatol 2011; 165:1244.
  8. Saracino A, Kelly R, Liew D, Chong A. Pyoderma gangrenosum requiring inpatient management: a report of 26 cases with follow up. Australas J Dermatol 2011; 52:218.
  9. Marzano AV, Damiani G, Ceccherini I, et al. Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis). Br J Dermatol 2017; 176:1588.
  10. Ortega-Loayza AG, Nugent WH, Lucero OM, et al. Dysregulation of inflammatory gene expression in lesional and nonlesional skin of patients with pyoderma gangrenosum. Br J Dermatol 2018; 178:e35.
  11. Ortega-Loayza AG, Friedman MA, Reese AM, et al. Molecular and Cellular Characterization of Pyoderma Gangrenosum: Implications for the Use of Gene Expression. J Invest Dermatol 2022; 142:1217.
  12. Lu JD, Milakovic M, Ortega-Loayza AG, et al. Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1. Expert Opin Investig Drugs 2020; 29:1179.
  13. Alberts JH, Sams HH, Miller JL, King LE Jr. Familial ulcerative pyoderma gangrenosum: a report of 2 kindred. Cutis 2002; 69:427.
  14. Khandpur S, Mehta S, Reddy BS. Pyoderma gangrenosum in two siblings: a familial predisposition. Pediatr Dermatol 2001; 18:308.
  15. al-Rimawi HS, Abuekteish FM, Daoud AS, Oboosi MM. Familial pyoderma gangrenosum presenting in infancy. Eur J Pediatr 1996; 155:759.
  16. Shands JW Jr, Flowers FP, Hill HM, Smith JO. Pyoderma gangrenosum in a kindred. Precipitation by surgery or mild physical trauma. J Am Acad Dermatol 1987; 16:931.
  17. Yeon HB, Lindor NM, Seidman JG, Seidman CE. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome maps to chromosome 15q. Am J Hum Genet 2000; 66:1443.
  18. Powell FC, Hackett BC, Wallach D. Pyoderma gangrenosum. In: Fitzpatrick's Dermatology in General Medicine, 8th ed, Goldsmith LA, Katz SI, Gilchrest BA, et al (Eds), McGraw-Hill Companies, Inc., 2012. Vol 1, p.371.
  19. Wong WW, Machado GR, Hill ME. Pyoderma gangrenosum: the great pretender and a challenging diagnosis. J Cutan Med Surg 2011; 15:322.
  20. Xia FD, Liu K, Lockwood S, et al. Risk of developing pyoderma gangrenosum after procedures in patients with a known history of pyoderma gangrenosum-A retrospective analysis. J Am Acad Dermatol 2018; 78:310.
  21. Callen JP, Jackson JM. Pyoderma gangrenosum: an update. Rheum Dis Clin North Am 2007; 33:787.
  22. Nico MM, Hussein TP, Aoki V, Lourenço SV. Pyostomatitis vegetans and its relation to inflammatory bowel disease, pyoderma gangrenosum, pyodermatitis vegetans, and pemphigus. J Oral Pathol Med 2012; 41:584.
  23. Brown TS, Marshall GS, Callen JP. Cavitating pulmonary infiltrate in an adolescent with pyoderma gangrenosum: a rarely recognized extracutaneous manifestation of a neutrophilic dermatosis. J Am Acad Dermatol 2000; 43:108.
  24. Fukuhara K, Urano Y, Kimura S, et al. Pyoderma gangrenosum with rheumatoid arthritis and pulmonary aseptic abscess responding to treatment with dapsone. Br J Dermatol 1998; 139:556.
  25. Abdelrazeq AS, Lund JN, Leveson SH. Pouchitis-associated pyoderma gangrenosum following restorative proctocolectomy for ulcerative colitis. Eur J Gastroenterol Hepatol 2004; 16:1057.
  26. Nurre LD, Rabalais GP, Callen JP. Neutrophilic dermatosis-associated sterile chronic multifocal osteomyelitis in pediatric patients: case report and review. Pediatr Dermatol 1999; 16:214.
  27. East-Innis A, Desnoes R, Thame K, et al. Pyoderma gangrenosum associated with osteomyelitis in a paediatric patient: a case report. West Indian Med J 2005; 54:207.
  28. Goldshmid O, Dovorish Z, Zehavi T, et al. Coexistent pyoderma gangrenosum and tibialis anterior myositis as presenting manifestations of Crohn's disease: case report and review of the literature. Rheumatol Int 2011; 31:525.
  29. Wilson DM, John GR, Callen JP. Peripheral ulcerative keratitis--an extracutaneous neutrophilic disorder: report of a patient with rheumatoid arthritis, pustular vasculitis, pyoderma gangrenosum, and Sweet's syndrome with an excellent response to cyclosporine therapy. J Am Acad Dermatol 1999; 40:331.
  30. Brown BA, Parker CT, Bower KS. Effective steroid-sparing treatment for peripheral ulcerative keratitis and pyoderma gangrenosum. Cornea 2001; 20:117.
  31. Teasley LA, Foster CS, Baltatzis S. Sclerokeratitis and facial skin lesions: a case report of pyoderma gangrenosum and its response to dapsone therapy. Cornea 2007; 26:215.
  32. Vadillo M, Jucgla A, Podzamczer D, et al. Pyoderma gangrenosum with liver, spleen and bone involvement in a patient with chronic myelomonocytic leukaemia. Br J Dermatol 1999; 141:541.
  33. Chanson P, Timsit J, Kujas M, et al. Pituitary granuloma and pyoderma gangrenosum. J Endocrinol Invest 1990; 13:677.
  34. Koester G, Tarnower A, Levisohn D, Burgdorf W. Bullous pyoderma gangrenosum. J Am Acad Dermatol 1993; 29:875.
  35. Scherlinger M, Guillet S, Doutre MS, et al. Pyoderma gangrenosum with extensive pulmonary involvement. J Eur Acad Dermatol Venereol 2017; 31:e214.
  36. Tolkachjov SN, Fahy AS, Wetter DA, et al. Postoperative pyoderma gangrenosum (PG): the Mayo Clinic experience of 20 years from 1994 through 2014. J Am Acad Dermatol 2015; 73:615.
  37. Ashchyan HJ, Butler DC, Nelson CA, et al. The Association of Age With Clinical Presentation and Comorbidities of Pyoderma Gangrenosum. JAMA Dermatol 2018; 154:409.
  38. Ahronowitz I, Harp J, Shinkai K. Etiology and management of pyoderma gangrenosum: a comprehensive review. Am J Clin Dermatol 2012; 13:191.
  39. Marzano AV, Trevisan V, Gattorno M, et al. Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene. JAMA Dermatol 2013; 149:762.
  40. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)--a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol 2012; 66:409.
  41. Marzano AV, Ishak RS, Colombo A, et al. Pyoderma gangrenosum, acne and suppurative hidradenitis syndrome following bowel bypass surgery. Dermatology 2012; 225:215.
  42. Marzano AV, Ceccherini I, Gattorno M, et al. Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases. Medicine (Baltimore) 2014; 93:e187.
  43. Koshelev MV, Garrison PA, Wright TS. Concurrent hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of the scalp, and pyoderma gangrenosum in a 16-year-old boy. Pediatr Dermatol 2014; 31:e20.
  44. Al Ghazal P, Herberger K, Schaller J, et al. Associated factors and comorbidities in patients with pyoderma gangrenosum in Germany: a retrospective multicentric analysis in 259 patients. Orphanet J Rare Dis 2013; 8:136.
  45. Jeong HS, Layher H, Cao L, et al. Pyoderma gangrenosum (PG) associated with levamisole-adulterated cocaine: Clinical, serologic, and histopathologic findings in a cohort of patients. J Am Acad Dermatol 2016; 74:892.
  46. Su WP, Davis MD, Weenig RH, et al. Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. Int J Dermatol 2004; 43:790.
  47. Maverakis E, Ma C, Shinkai K, et al. Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of International Experts. JAMA Dermatol 2018; 154:461.
  48. Jockenhöfer F, Wollina U, Salva KA, et al. The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum. Br J Dermatol 2019; 180:615.
  49. Weedon D. The vasculopathic reaction pattern. In: Weedon's Skin Pathology, 3rd ed, Elsevier Limited, 2010. p.195.
  50. Weenig RH, Davis MD, Dahl PR, Su WP. Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med 2002; 347:1412.
  51. Sanchez IM, Lowenstein S, Johnson KA, et al. Clinical Features of Neutrophilic Dermatosis Variants Resembling Necrotizing Fasciitis. JAMA Dermatol 2019; 155:79.
  52. Touil LL, Gurusinghe DA, Sadri A, et al. Postsurgical Pyoderma Gangrenosum Versus Necrotizing Fasciitis: Can We Spot the Difference? Ann Plast Surg 2017; 78:582.
  53. Hradil E, Jeppsson C, Hamnerius N, Svensson Å. The diagnosis you wish you had never operated on: Pyoderma gangrenosum misdiagnosed as necrotizing fasciitis-a case report. Acta Orthop 2017; 88:231.
  54. Berger N, Ebenhoch M, Salzmann M. Postoperative Pyoderma Gangrenosum in Children: The Case Report of a 13-Year-Old Boy With Pyoderma Gangrenosum After Hip Reconstruction Surgery and a Review of the Literature. J Pediatr Orthop 2017; 37:e379.
Topic 13782 Version 18.0

References

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