Abstract
Introduction
We report a case of pyoderma gangrenosum associated with Crohn’s disease in a teenage Malawian boy who had a chronic history of painful scalp, lower limb ulcers, recurrent bloody diarrhoea and growth stunting. After a six-year period of diagnostic delay and mismanagement, typical clinical features and confirmatory laboratory findings established the diagnoses and to initiate appropriate therapy which resulted in rapid improvement in both cutaneous and bowel symptoms. This challenges clinicians to consider pyoderma gangrenosum in any child with chronic ulceration especially where systemic manifestations of commonly associated co-morbidities co-exist.
Case report
A 16-year-old boy was admitted to Queen Elizabeth Central Hospital, Malawi with a four-week history of very painful, slow-growing ulcers on the dorsal aspects of both feet and on the scalp, which started as painful pustules that later ruptured. They were preceded by bloody diarrhoea but he had no associated joint pain, fever or night sweats. This was his fourth admission in six years with similar complaints. In the first admission five years prior, he received anti-tuberculosis therapy for a clinical diagnosis of cutaneous tuberculosis; in the second admission, intravenous antibiotics for pyodermic ulcers were given after histology had excluded malignancy. In the third admission, he was managed for ‘tropical ulcers’ by wound dressing and later split skin grafting following which margins of the grafted sites broke down while the donor sites healed with scarring. There was no other relevant past history. On examination, he was in pain, afebrile, looked small for his age with severe wasting (BMI = 13.3 kg/m2) and stunting (height = 1.5 m), and had mucocutaneous pallor. The ulcers were erythematous with irregular, elevated but undermined edges, had infiltrated bases with purulent necrotic tissues interspersed with pink granulation tissue and were tender to touch. The right foot ulcer measured 8 × 9 cm, the left foot ulcer 18 × 10 cm and the occipital ulcer had a diameter of 13 cm. He had atrophic and cribriform scars on his thighs and medial aspects of his left knee from previous graft harvesting and ulceration, respectively (Figures 1–3), and had oral aphthous ulcers. The perianal skin, respiratory, cardiovascular, neurological and abdominal examinations were normal.
Foot ulcers. Scalp ulcer. Scarring.
Investigations
Pus cultures from the ulcer base were negative. Full blood count showed microcytic anaemia of 4.6 g/dL, leucocyte count of 10.4 × 109/µL and platelet count of 549 × 103/µL. Erythrocyte sedimentation rate (ESR) was raised (78 mm/h). The following tests were either normal or negative: liver and renal function tests; human immunodeficiency virus; hepatitis B and C and syphilis serology; stool microscopy; chest radiography; and abdominal ultrasound scan. Histology of the ulcers was not repeated. Colonoscopy revealed a florid aphthoid erosive sigmoiditis with early pseudo-polyp formation and cobble-stoning (Figure 4). Colonic biopsy revealed a chronic active colitis with cryptitis and crypt architecture alteration. The lamina propria was expanded by an inflammatory infiltrate composed of lymphocytes, numerous plasma cells and some neutrophils. Infective agents or granulomas were not identified and malignancy was not present. This was suggestive of Crohn’s disease.
Colonoscopy appearances.
Diagnosis and treatment
Based on the history, examination and investigative findings, a diagnosis of pyoderma gangrenosum (PG) associated with Crohn’s disease was made. Oral prednisolone (1 mg/kg) resulted in rapid clinical improvement of both bowel and cutaneous symptoms within one week. Azathioprine 50 mg once daily was then added while tapering steroids. Blood transfusion was given and malnutrition was treated according to local hospital protocols. He was discharged on the same medications with regular outpatient clinic follow-up during which time he continues to improve.
Discussion
PG is a neutrophilic dermatosis with an aberrant and possibly autoimmune response that affects people of all age groups. Approximately 4% of patients are children. 1 It appears in 0.5–2% of patients with inflammatory bowel disease (IBD). 2 In children, IBD is the co-morbidity most commonly associated with PG. Others include arthritis and leukaemia. 3 Such co-existence with other immune-mediated diseases provides evidence of possible underlying immune aetiology. 4 Classically, PG starts as painful papulo-pustules which rapidly evolve into painful ulceration with undermined edges. Lesions may occur anywhere but, while more common on pretibial areas in adults, location on atypical sites like head and neck is frequent in paediatric PG. 3 Four PG clinical variants have been described: classical (ulcerative); pustular; bullous; and vegetative. 5 Worsening of ulceration may occur at sites of trauma like biopsy, surgery and cannulation. This phenomenon occurs in 20% of patients and is called pathergy. As it lacks specific diagnostic markers, PG is a diagnosis of exclusion using set diagnostic criteria. 6 Diagnosis is made in the presence of both major criteria (1 = a sterile pustule or ulcer with undermined borders; 2 = exclusion of alternative diagnoses of ulceration) and at least two minor criteria (1 = cribriform scarring or history suggestive of pathergy; 2 = histopathology showing sterile dermal neutrophilia; 3 = underlying systemic disease associated with PG; 4 = rapid response to systemic immunosuppressive therapy; 5 = extremely painful ulcer out of proportion to its size). In our patient, both major criteria and all minor criteria were met. In addition, the history of lower gastrointestinal tract (GIT) bleed, oral ulceration, anaemia, raised non-specific inflammatory markers (platelets and ESR) and failure to thrive in the absence of other known cause raised our clinical suspicion of IBD which we were able to confirm by endoscopy of lower GIT and histopathology of intestinal mucosa.7–9 The mainstay of treatment of PG is immunosuppressive and immunomodulatory drugs such as corticosteroids, cyclosporine A and dapsone. 10 Where possible, treatment of underlying condition will prevent risk of rebound flares but therapy is generally difficult and relapses may occur. 3
Conclusion
PG is a rare, chronic disease whose non-specific presentation may result in considerable diagnostic delays by non-suspecting clinicians. A six-year delay characterised with unnecessary interventions in our patient was followed by rapid improvement upon starting right therapy once diagnosis was confirmed from suspicious clinical features. This challenges clinicians to consider PG among causes of ulceration in children, especially if co-existent systemic manifestations are present to avoid complications.
Footnotes
Acknowledgements
The authors thank their colleagues in the paediatrics department for their helpful contribution in the care of this patient.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.