Case Series
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Clinico-histopathological Features of Pyoderma Gangrenosum: A Case Series |
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Moxda Suresh Patel, Digisha Hamirbhai Jotva, Niraj Virendrabhai Dhinoja, Riya Pravinbhai Patel, Neela Madhubhai Patel 1. Assistant Professor, Department of Pathology, Ahmedabad Municipal Corporation’s Medical Education Trust Medical College, Ahmedabad, Gujarat, India. 2. First Year Resident, Department of Pathology, Ahmedabad Municipal Corporation’s Medical Education Trust Medical College, Ahmedabad, Gujarat, India. 3. Second Year Resident, Department of Dermatology, Ahmedabad Municipal Corporation’s Medical Education Trust Medical College, Ahmedabad, Gujarat, India. 4. Second Year Resident, Department of Pathology, Ahmedabad Municipal Corporation’s Medical Education Trust Medical College, Ahmedabad, Gujarat, India. 5. Professor and Head, Department of Dermatology, Ahmedabad Municipal Corporation’s Medical Education Trust Medical College, Ahmedabad, Gujarat, India. |
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Correspondence
Address : Riya Pravinbhai Patel, 70, Suramya Bunglows, Near Murlidhar Party Plot, Science City Road, Sola, Ahmedabad, Gujarat, India. E-mail: riyap6874@gmail.com |
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ABSTRACT | |||||||||||||||||||||||||||||||||||||||||||||||
Pyoderma Gangrenosum (PG) is a rare, ulcerative, non infectious neutrophilic inflammatory dermatosis and often associated with underlying systemic disorder. The incidence of PG is estimated to be 0.63 per 1,00,000 with the median age at presentation of 59 years. Among its clinical variants, classical PG is the most common. The diagnosis of PG can be difficult. This case series was an attempt to review the new trends for the diagnosis of PG and also to compare them with previous diagnostic criteria. Previously histopathological criteria were included as minor criteria in Su WP et al., classification. More recently proposed diagnostic criteria by Maverkis E et al., include histopathology of skin biopsy from edge of ulcer showing neutrophilic infiltration as a major criteria. Aim of the study is to correlate and stamp the clinically suspected cases of PG with help of histopathology. This retrospective observational case series study was conducted in a tertiary care hospital from May 2018 to April 2020 consisting of 19 cases (15 years to 68 years of age range; 13 males and 6 females). Detailed history, clinical examination and blood investigations were done in all suspected cases of PG followed by histopathological examination of skin biopsy. In 17 cases, lesions were located in lower limb, one case each in buttocks and lower abdomen. The classical, ulcerative form found in 12 cases (63.15%), vegetative form in 3 cases (15.78%), plaque and bullae form were in 2 cases each (10.52%). Pathergy test was positive in 11 cases (57.89%). Histopathological examination showed neutrophilic infiltration in all 19 cases (100%), vasculitis in 11 patients (57.89%), lymphoplasmacytic infiltrate in 6 patients (31.57%), pseudoepitheliomatous hyperplasia in 5 patients (26.31%), mixed inflammatory infiltrate in 4 patients (21%), Epidermal ulceration in 4 patients (21%) and mitosis is seen in 3 patients (15.78%). Histopathology is considered as a main tool which helps clinicians to stamp suspected cases of PG. | |||||||||||||||||||||||||||||||||||||||||||||||
Keywords : Leukocytoclastic vasculitis, Neutrophilic infiltration, Panniculitis, Ulcer | |||||||||||||||||||||||||||||||||||||||||||||||
INTRODUCTION | |||||||||||||||||||||||||||||||||||||||||||||||
Pyoderma Gangrenosum (PG), first described by Brocq in 1916 and named by Brunsting et al., in 1930 as is mentioned in study by Bhat RM et al., (1). It is a reactive, non infectious neutrophilic inflammatory dermatosis that typically presents as rapidly progressive, painful, necrotic ulcer with ragged undermined edge with erythematous border. The incidence of PG is estimated to be 0.63 per 1,00,000 with the median age at presentation of 59 years (2). It has a predilection for lower extremities although it can present at any site of body. PG can occur at any age, but generally presents in the second to fifth decade of life. The lesion may be precipitated by minor trauma, a phenomenon known as ‘Pathergy’ (3). Pathophysiology of PG is not well understood but loss of innate immune regulation and altered neutrophil chemotaxis are believed to be involved to some extent (4). Underlying systemic conditions like inflammatory bowel diseases, rheumatoid arthritis and some haematological malignancies are found in 50% cases of PG (5). Classical PG is most common form (approximately 85%) but other clinical variants include pustular, bullous, vegetative and superficial granulomatous (1). Aim of skin biopsy was to exclude other causes of cutaneous ulceration such as infection, vasculitis (Wegener granulomatosis, Chrugstrauss syndrome, Behcet disease), malignancies (cutaneous lymphoma, leukaemia, basal cell carcinoma, squamous cell carcinoma), as histopathology is a main tool according to improved Maverakis criteria to diagnose suspected cases of PG (6), It will also help the clinician to confirm the diagnosis of PG and expand the available literature. | |||||||||||||||||||||||||||||||||||||||||||||||
CASE REPORT | |||||||||||||||||||||||||||||||||||||||||||||||
The present case series with retrospective observational design was conducted in the Department of Pathology at Ahmedabad Municipal Corporation’s Medical Education Trust Medical College, Sheth Lallubhai Gordhandas Municipal Hospital, Ahmedabad, Gujarat, India, over a period of two years from May 2018 to April 2020. This study got approval from Institutional Review Board, AMC MET Medical College on 29th December 2020. All biopsies from skin lesions which were clinically suspicious of PG and confirmed histopathologically were included in the study. Inadequate biopsy material was excluded from study. Relevant clinical information (e.g., age, sex, site of lesions, associated diseases, pathergy test results and clinical types of PG) was obtained from case reports of all the included patients (Table/Fig 1). Skin pathergy test was done in all patients on volar aspects of forearm. Skin prick was done using 16 gauge needle, inserted at 45 degree and read after 48 hours. Development of papule or pustule consider as a positive test (7). All the biopsies suspected as PG by Dermatology Department were processed, cut and stained by Haematoxylin and Eosin (H&E). Then they were evaluated histopathologically. Total 19 cases were identified by clinical findings and histopathological features consistent with PG together with haematological, biochemical and microbiological investigations to rule out the other causes of cutaneous ulceration. • Out of 19 patients 13 were males and 6 were females; sex ratio M:F=2.2:1. Majority of patients in this case series were between 15 to 50 years. • The classical, ulcerative form (Table/Fig 2) was found in 12 cases (63.15%), vegetative form (Table/Fig 3) in 3 cases (15.78%), plaque and bullae form (Table/Fig 4) were in 2 cases each (10.52%). • Lesions were mainly located in lower limbs in 17 cases, buttocks and lower abdomen in one case each. Pathergy test was positive in 11 cases (57.89%). • Histopathological examination showed a neutrophilic infiltrate (Table/Fig 5),(Table/Fig 6) in all 19 patients (100%), vasculitis in 11 patients (57.89%), lymphoplasmacytic infiltrate in 6 patients (31.57%), pseudoepitheliomatous hyperplasia in 5 patients (26.31%), mixed inflammatory infiltrate in 4 patients (21%), Epidermal ulceration in 4 patients (21%) and mitosis is seen in 3 patients (15.78%) (Table/Fig 7). • Associated disease with PG were found in 9 cases (47.36%), out of which diabetes mellitus in 3 cases (15.78%), Inflammatory arthritis, ulcerative colitis and hypertension in 2 cases each (10.52%), hypothyroidism and bacterial infection in 1 case each (5.2%). Some of the cases show more than one co-morbidity. • One patient developed cutaneous squamous cell carcinoma after three years of disease onset. | |||||||||||||||||||||||||||||||||||||||||||||||
DISCUSSION | |||||||||||||||||||||||||||||||||||||||||||||||
Pyoderma Gangrenosum (PG) was first described by Brocq in 1916 as “phagedenismegeometrique” and later named by Brunsting et al., and they considered PG to be the dissemination of a distant focus of infection (i.e., the bowel in ulcerative colitis or lungs in empyema). Presently PG is considered a reactive inflammatory dermatosis (1),(8). PG clinically can mimic other cutaneous ulcerative disease such as vaso-occlusive and venous disease, infections, vasculitis, lymphoma, leukaemia, other neutrophilic dermatosis such as atypical sweet’s syndrome, Behcet’s disease. The histopathological distinction of PG from other ulcerative diseases is by neutrophilic infiltrate at the edge of ulcer. According to previous diagnostic criteria proposed by Su WP et.al. and Von Den Driesch P, mainly depends on recognition of the evolving clinical features [Table/Fig-8,9] (9),(10). In Su WP et al., criteria, major criteria for diagnosis of PG is rapid progression of a painful necrotic cutaneous ulcer with irregular, violaceous, undermined border and exclusion of other causes of cutaneous ulceration that will lead to overdiagnosis as it is also present in other ulcerative disorder. But more recently Maverakis E et al., proposed a new criteria (Table/Fig 10), it include histopathology of skin biopsy from edge of ulcer showing neutrophilic infiltration as a major criteria which is yet to be widely adopted (6). Histological findings can be variable among different variants of PG (Table/Fig 11) (11). Initially, lesions of PG presents as a papulopustule that microscopically has a changes of folliculities involving a pilosebaceous unit with dense neutrophilic infiltrate. The perifollicular dermis frequently contains keratinous debris, hair shaft fragments, squames and dense aggregation of neutrophils. Intraepidermal and subcorneal collection of neutrophils also seen. Frequently adjacent blood vessels show changes of leukocytoclastic vasculitis like neutrophils within and around disrupted blood vessels, extravasated red blood cells and necrosis of endothelial cells. Pustule evolves into noduloplaque that microscopically has changes of suppurative granulomatous dermatitis and panniculitis. Massive papillary dermal oedema with epidermal neutrophilic abscess and spongiosis is seen. Regressing lesion have a mononuclear cell infiltrates of lymphocytes and histiocytes and finally a fibroplasia (12). PG may occur at any age but in this study maximum patients were found between 15 to 50 years (78.9%) with a male predominance (13), classical ulcerative form is most common (63.15%) but other clinical variants like plaque, bullae and vegetative are rare. Classical ulcerative form can occur at any site of the body but most commonly it is found in lower extremities (83.33%). The reason for this specific location is not known (14). Binus AM et al., found that almost one-third patients had co-morbid conditions such as diabetes and peripheral vascular disease, this two diseases might play role in development of PG and worsen the local healing (15). Neutrophilic infiltration is present in all cases, which is comparable to other studies of Hurwitz RM and Haseman JH, and Chakiri R et al., (Table/Fig 12) (16),(17),(18). Chakiri R et al., found that ulcers of classical subtype favor the lower extremities in upto 85.7% of patients and disease association in 42.85%, which is comparable to the present study. Associated disease at diagnosis of PG were found in 9 cases (47.36%) (18). Investigations are necessary to determine treatable, systemic, associated diseases (19). Aetiology of PG is not well understood; therefore, no specific therapy is available. Aim of treatment is to reduce pain and promote wound healing by reducing inflammation by anti-inflammatory and immunosuppressive agents to improve quality of life of patients of PG. Immunosuppressive therapy is the mainstay in the treatment of PG. Treatment of underlying disease aid in healing. Because of rarity of PG and ethical consideration, there is no placebo controlled trials in treatment of PG. Local therapy- wet compresses with saline and alginate dressings are useful. Topical agents such as tacrolimus, potent corticosteroids and cyclosporine are used (20). Phenytoin solution 2% is beneficial. Systemic corticosteroids therapy is the most effective treatment of acute, rapidly progressive form. A high dose of prednisolone or pulse therapy with dexamethasone is useful in resistant disease (21). Cyclosporine as an immunosuppressant is useful in steroid resistant PG. Sulfa drugs may be used as a steroid sparing agent. Recently, use of Tumor Necrosis Factor (TNF)-alpha blockers and other injectable biologics are successful. Infliximab and adalimumab are also effective in treatment of PG (22). PG is a rare disorder and recruiting large number of patient is difficult. Thus, multicenter studies with large number of patients are required for confirmation of results of study. Patient recruitment was done only by Dermatology Department which was a selection bias. Thus, involvement of other specialists is also required. | |||||||||||||||||||||||||||||||||||||||||||||||
CONCLUSION | |||||||||||||||||||||||||||||||||||||||||||||||
Pyoderma Gangrenosum (PG) is a unique disease in terms of clinical presentation and histopathology. It has variable course from its origin and during its progression. Ulcerative PG is the most common type of PG. More than half of the patients had associated systemic disease and positive pathergy test. PG should be regarded as a syndrome that presents with a spectrum of clinical and histopathological features that are clear, distinct and exhibit characteristic microscopic findings throughout its evolution. In Indian patients, Maverakis criteria should be used, in clinically suspected cases of PG with its histopathological characteristics and excluding other causes of infections. | |||||||||||||||||||||||||||||||||||||||||||||||
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