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Granulomatosis con poliangeítis y úlceras cutáneas simuladoras de pioderma gangrenoso: reporte de caso de un reto diagnóstico
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The aim of this study was to determine the prevalence and type of cutaneous manifestations which occur in patients with granulomatosis with polyangiitis and to explore the potential association between cutaneous and systemic involvement in these patients. A retrospective case series study was designed, including all granulomatosis with polyangiitis cases diagnosed between 2010 and 2018 at the Hospital Universitario Virgen de las Nieves. Thirty-nine patients with granulomatosis with polyangiitis were identified, of which 53.85% presented cutaneous manifestations. In decreasing order of frequency, the types of cutaneous problems observed included: palpable purpura, mucocutaneous ulcers, subcutaneous nodules, pyoderma gangrenosum-like ulcers, digital necrosis, papulonecrotic lesions and livedo reticularis. Patients with palpable purpura presented a higher frequency of renal involvement (p = 0.008). Cutaneous manifestations of granulomatosis with polyangiitis may facilitate early disease diagnosis. Likewise, a manifestation such as palpable purpura may be a predictor of kidney damage.
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing small vessel vasculitis associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Skin manifestations, mostly represented by palpable purpura, papulonodular lesions and livedo reticularis, are present in up to 50% of the cases. Ulcerations with undermined, raised erythematous–violaceous border resembling pyoderma gangrenosum (PG) have rarely been reported as skin involvement in GPA. The presence of circulating ANCAs with a cytoplasmic labelling pattern, the involvement of internal organs, particularly of the lung, and the absence on histology of a mainly neutrophilic infiltrate in early phases of the cutaneous lesions may be regarded as clues to rule out true PG and confirm the diagnosis of GPA skin ulcerations simulating PG. Herein, we describe two paradigmatic cases of such a unique presentation of GPA and a literature review focusing on clinicopathological features of GPA presenting with PG-like ulcerations in the skin has been provided. Moreover, referring to the scenario observed in these two cases, an easy-to-use working approach for the differential diagnosis between the two conditions has also been proposed.
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), is a rare systemic vasculitis that classically manifests as necrotizing granulomas of the upper and lower respiratory tract, kidneys, and blood vessels; however, it may affect any organ system, including the skin. Cutaneous manifestations occur in up to 45% of patients during the disease course, and are the presenting feature in 9% to 14% of patients. The most common skin lesion specific to GPA is palpable purpura, with the histopathologic correlate of leukocytoclastic vasculitis. However, a wide range of clinical and histologic features may be seen. We herein report a case of a previously healthy 52-year-old Caucasian man who presented with multiple progressively enlarging painful ulcers on his face, upper extremities, back, and abdomen over a two-month period. Skin biopsies revealed pyoderma gangrenosum-like features. Serological tests were positive for PR3/c-ANCA. Six months later, the patient developed recurrent episodes of sinusitis associated with nasal bleeds and eventually nasal septum perforation. Despite aggressive treatment with Cyclophosphamide and steroids over one year, the patient had persistent nonhealing large ulcers and developed multiple lung nodules with cavitary lesions.
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG is often associated with a variety of other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis. The cause of PG is not well understood, but PG is generally considered an autoinflammatory disorder. Studies have focused on the role of T cells, especially at the wound margin; these cells may support the destructive autoinflammatory response by the innate immune system. PG is difficult to diagnose as several differential diagnoses are possible; in addition to clinical examination, laboratory tests of biopsied wound tissue are required for an accurate diagnosis, and new validated diagnostic criteria will facilitate the process. Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) to reduce inflammation followed by the addition of more slowly acting immunosuppressive drugs with superior adverse event profiles, including biologics (in particular, anti-tumour necrosis factor (TNF) agents). Appropriate wound care is also essential. Future research should focus on PG-specific outcome measures and PG quality-of-life studies. Pyoderma gangrenosum is a rare, non-infectious, inflammatory skin condition characterized by rapidly developing, painful ulcers. This Primer provides an overview of the epidemiology, pathophysiology, diagnosis and treatment of the disease.
Importance Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a “diagnosis of exclusion,” a definition not compatible with clinical decision making or inclusion for clinical trials.
Objective To propose and validate diagnostic criteria for ulcerative pyoderma gangrenosum.
Evidence Review Diagnostic criteria were created following a Delphi consensus exercise using the RAND/UCLA Appropriateness Method. The criteria were validated against peer-reviewed established cases of pyoderma gangrenosum and mimickers using k-fold cross-validation with methods of multiple imputation.
Findings Delphi exercise yielded 1 major criterion—biopsy of ulcer edge demonstrating neutrophilic infiltrate—and 8 minor criteria: (1) exclusion of infection; (2) pathergy; (3) history of inflammatory bowel disease or inflammatory arthritis; (4) history of papule, pustule, or vesicle ulcerating within 4 days of appearing; (5) peripheral erythema, undermining border, and tenderness at ulceration site; (6) multiple ulcerations, at least 1 on an anterior lower leg; (7) cribriform or “wrinkled paper” scar(s) at healed ulcer sites; and (8) decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Receiver operating characteristic analysis revealed that 4 of 8 minor criteria maximized discrimination, yielding sensitivity and specificity of 86% and 90%, respectively.
Conclusions and Relevance This Delphi exercise produced 1 major criterion and 8 minor criteria for the diagnosis of ulcerative pyoderma gangrenosum. The criteria may serve as a guideline for clinicians, allowing for fewer misdiagnoses and improved patient selection for clinical trials.
Granulomatosis with polyangitis, formerly known as Wegener's granulomatosis, is a multi-system vasculitis that has a variable clinical presentation. Although uncommon, cutaneous symptoms can be the initial presenting symptom of granulomatosis with polyangitis. We present an unusual case of pyoderma gangrenosum followed by a diagnosis of granulomatosis with polyangitis. We also provide a review of current literature on therapeutic options.
Background:
The risk of postoperative pyoderma gangrenosum (PG) in patients with a known history of PG is unknown.
Objective:
To quantify risk and identify patient/procedure-related risk factors for postsurgical PG recurrence/exacerbation in patients with known history of PG.
Methods:
We retrospectively evaluated the likelihood of postsurgical PG recurrence/exacerbation for all patients with a confirmed diagnosis of PG at Brigham & Women's Hospital and Massachusetts General Hospital from 2000-2015.
Results:
5.5% (n=33) of procedures led to recurrence of PG in 15.1% (n=25) of patients. Compared to skin biopsy, small open surgeries had an adjusted odds ratio (aOR) of 8.65 (1.55, 48.33) for PG recurrence/exacerbation; large open surgeries had an aOR of 5.97 (1.70, 21.00); and Mohs surgery/skin excision had an aOR of 6.47 (1.77, 23.61). PG chronically present at the time of procedure had an aOR of 4.58 (1.72, 12.22). Immunosuppression, time elapsed since original PG diagnosis, and procedure location did not significantly influence risk.
Limitations:
Our study is limited by its retrospective nature and relatively small sample size.
Conclusion:
There is a small but clinically meaningful risk of postsurgical PG recurrence/exacerbation in patients with known history of PG; higher risks occur with more invasive procedures and chronically present PG.
Granulomatosis with polyangiitis (GPA), a vasculitis that most commonly affects small to medium-size vessels of the respiratory tract and kidneys, may also present with a wide array of skin findings. We present the case of a 12-year-old boy with pyoderma gangrenosum–like ulcerations on his lower extremity as the initial manifestation of GPA despite negative cytoplasmic antineutrophilic cytoplasmic antibodies (c-ANCAs). Although GPA is strongly associated with c-ANCA, c-ANCA may be negative on presentation. Thus clinical and pathologic clues must be relied upon when serologic confirmation is negative.
Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the genetic basis of PG and the role of auto-inflammation provides a better understanding of the disease and new therapeutic targets. PG equally affects patients of both sexes and of any age. Uncontrolled cutaneous neutrophilic inflammation is the cornerstone in a genetically predisposed individual. Multimodality management is often required to reduce inflammation, optimize wound healing, and treat underlying disease. A gold standard for the management of PG does not exist and high-level evidence is limited. Multiple factors must be taken into account when deciding on the optimum treatment for individual patients: location, number and size of lesion/ulceration(s), extracutaneous involvement, presence of associated disease, cost, and side effects of treatment, as well as patient comorbidities and preferences. Refractory and rapidly progressive cases require early initiation of systemic therapy. Newer targeted therapies represent a promising pathway for the management of PG, and the main focus of this review is the management and evidence supporting the role of new targeted therapies in PG.
Introduction:
Granulomatosis with polyangiitis is a systemic and necrotizing vasculitis, and cutaneous involvement is uncommon. We report two cases of skin ulceration mimicking a pyoderma gangrenosum, and revealing granulomatosis with polyangiitis.
Case reports:
We report two patients who presented with atypical cutaneous ulcerations, with a chronic course. These wounds were large ulcerations with abrupt edges, with purulent and hemorrhagic exudates. The first hypothesis was a pyoderma gangrenosum, but the biopsies were not specific. New biopsies performed distant from the edges showed a necrotizing vasculitis associated with giant cells granuloma, typical from granulomatosis with polyangiitis.
Conclusion:
Cutaneous manifestations are uncommon in granulomatosis with polyangiitis, and can be misleading as they may precede the systemic symptoms. We report two cases of granulomatosis with polyangiitis revealed by cutaneous symptoms mimicking a pyoderma gangrenosum. Repetition of the skin biopsies were necessary to obtain the diagnosis.
Granulomatosis with polyangiitis (GPA) is a rare systemic vasculitis associated with variable cutaneous manifestations and histopathologic findings. It is less frequent in children than adults and is often positive for cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or proteinase 3-ANCA.
We sought to better define and correlate the clinical, histopathologic, and immunopathologic characteristics of cutaneous GPA in pediatric patients.
We retrospectively reviewed clinical records and cutaneous histopathologic specimens of patients 17 years or younger with cutaneous manifestations of GPA who were seen at our institution from 1990 to 2013.
Of the 52 patients identified with GPA, cutaneous involvement occurred in 36.5% and was the initial manifestation of disease in 7.7%. Of the 19 patients with cutaneous involvement, 26.3% developed acneiform and folliculitis-like papules; 84.2% were cytoplasmic ANCA positive; and 78.9% were proteinase 3-ANCA positive. Histopathologic features included leukocytoclastic vasculitis, granulomatous inflammation, acneiform and perifollicular inflammation, granulomatous vasculitis, and palisading granulomas.
Our study was limited because of its retrospective design.
Pediatric patients with cutaneous GPA most commonly have palpable purpura, leukocytoclastic vasculitis, and positive cytoplasmic ANCA or proteinase 3-ANCA serologic results. Cutaneous manifestations and histopathologic findings vary, but acneiform lesions may be a cutaneous manifestation of the disease unique to this age group.
Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
A 46-year-old man, without remarkable past medical history, had a perianal ulcer that appeared spontaneously two months before presentation. At admission, the ulcer was painless, measuring 4 to 5 cm in diameter and showing detachment and a slightly papillomatous aspect at the edge but without induration of the base. Microscopic examination revealed cutaneous ulceration with a well-developed inflammatory response, a few small vessels with intraluminal thrombosis or necrotizing walls, and isolated microscopic granulomata. No infectious disease was detected. The diagnosis of Wegener's granulomatosis was made six months later, when the disease was clinically evident in three principal sites: upper airways, lung, and kidney. At that time, serum antineutrophil cytoplasmic autoantibodies were detected with indirect immunofluorescence microscopy. There has been an excellent response to immunosuppressive therapy. Review of the literature revealed no similar reports.
Pyoderma gangrenosum (PG) is an uncommon and challenging disease, highly associated with comorbidities, but poorly characterized from a diagnostic and therapeutic perspective.
To describe the epidemiology of PG in a hospital-based retrospective review, focusing on demographics, comorbidities and treatments.
We conducted a retrospective chart review. Patient data were taken from the Research Patient Data Repository of Brigham and Women's Hospital and Massachusetts General Hospital from 1 January 2000 to 31 December 2007. We identified and confirmed 103 cases of PG, and collected data on anatomical location, number and size of the PG lesions, patient demographics, comorbidities, mortality rate and treatments.
Of the 103 patients, 78 (76%) were female, and only 7% had a biopsy suggestive of PG. The lower leg was the most common location with 78% of PG ulcers occurring there, and 67 (65% of patients) had two or more ulcers at some point. Thirty-five individuals (34%) had inflammatory bowel disease (IBD), 21 (20%) had haematological disorders, 14 (14%) had major depression, 20 (19%) had seronegative arthritis, 11 (11%) had psoriasis, and nine (9%) had hepatitis. Therapy was generally multimodal. The mortality rate during the 8-year study period was 16%.
We present one of the largest PG case series to date. In our study, we found that biopsy of a PG lesion rarely yielded characteristic features of the disease and tissue pathology should not be used to exclude a PG diagnosis. We also found a female predominance and associations with IBD and haematological disorders. Patients with PG in this series had high rates of depression and hepatitis. Further work is needed to establish the mechanism(s) underlying these findings.
We report three cases of Wegener's granulomatosis presenting with cutaneous ulceration resembling pyoderma gangrenosum. Wegener's granulomatosis classically affects the upper and lower respiratory tracts and the kidneys. Skin involvement occurs in up to 50% of patients. Increased awareness that cutaneous involvement can take the form of pyoderma gangrenosum and that it can be a presenting sign may lead to more rapid diagnosis of Wegener's granulomatosis.
Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous inflammation and vasculitis. Its cutaneous manifestations vary.
We reviewed and characterized the clinical, pathologic, and immunopathologic features of the specific cutaneous manifestations of WG and investigated the sensitivity and the specificity of anti-neutrophilic cytoplasmic antibody (c-ANCA) in the cutaneous manifestations of this disease.
A retrospective analysis was conducted of 244 cases of WG observed between 1988 and 1992.
Skin involvement occurred in 14% of the patients and was more frequent in generalized WG. Skin lesions may be an early premonitory sign of renal disease. Necrotizing ulcerations resembling pyoderma gangrenosum were not uncommon. Leukocytoclastic vasculitis was the most common cutaneous pathologic pattern. Findings of c-ANCA were positive in 81% of patients with cutaneous WG.
Skin involvement usually occurred at presentation with generalized disease. c-ANCA is a valuable adjunct to diagnosis and follow-up of WG.
A 27-year-old woman presented with a right infra-auricular noduloulcerative lesion progressing to a peri-auricular pyoderma gangrenosum-like ulcer with destruction of her right earlobe over an 8-month period. Similar nodules appeared on the right malar and left infra-auricular regions. The cutaneous manifestations were associated with nasal congestion, rhinorrhoea and serosanguineous nasal crusting. Skin biopsy demonstrated suppurative granulomatous inflammation. Investigation of both renal and pulmonary function showed no abnormality. Serological testing revealed a positive cytoplasmic pattern antineutrophil cytoplasmic antibody with high proteinase-3 specificity, which in conjunction with the clinical findings is consistent with a diagnosis of protracted superficial Wegener's granulomatosis. Initial treatment with prednisone 1 mg/kg/day and azathioprine 100 mg/day resulted in complete resolution of her lesions. Reduction of the corticosteroid dose below 0.3 mg/kg/day led to recrudescence of cutaneous and upper respiratory tract symptoms, at which stage methotrexate was substituted for azathioprine with rapid induction of remission and further prednisone withdrawal. Thirty-two months after the initial diagnosis the patient remains well with no other organ involvement.
We report a case of an unusual presentation of Wegener's granulomatosis (WG) in a patient with Crohn's disease (CD). She presented to our Wound Care Center with 7th cranial nerve palsy and facial pyoderma-like ulcerations. Although WG has a predilection for the lung, kidney, and eyes, cutaneous involvement can be seen in 50% of the cases, and it can be the presenting sign in 9-14%. Because of the lethality of WG if not properly treated, the diagnosis is imperative.
Wegenersche granulomatose unter dem klinischen bild eines pyoderma gangraenosum
- Boudny