Gastro-intestinal Manifestations in Granulomatosis with Polyangiitis: A Less Common Encountered Entity with Brief Review

Dear Editor,

Granulomatosis with polyangiitis (GPA) is a multisystem disorder causing necrotizing granulomatous inflammation of small and medium vessels predominantly involving the respiratory tract and kidneys, although any organ system can be involved.[1]

Gastrointestinal tract (GI) involvement is seen in 5–11% of patients and manifestations can vary from abdominal pain to life-threatening complications like massive bleeding and hemorrhage.[2]

Herein, we report a case of GPA in a young woman with cutaneous, ocular, renal, and GI involvement.

A 21-year-old female, with no significant comorbidity presented to the dermatology department with recurrent episodes of cutaneous lesions in the form of grouped papules, vesicles, and partially blanchable purpura over both upper and lower extremities, and lower abdomen for 1.5 years. Some lesions would eventually ulcerate and heal with atrophic scarring. The patient was on irregular therapy over the past year.

Cutaneous examination findings are shown in Figure 1a–d.

Figure 1.

(a) Necrotic ulcers, atrophic scarring, postinflammatory hyperpigmentation over lower limbs. (b) Multiple grouped erythematous, nontender papules over upper limb. (c) Bullae over lower limbs. (d) Dusky-erythematous, nontender papules, and plaques over palms

She had a history of easy fatiguability, weight loss, joint pains primarily of both lower limbs, and recurrent episodes of redness of the eyes. There was no history of fever, photosensitivity, oral ulcerations, upper respiratory symptoms, abdominal pain, decreased urine output, headaches, and otologic complaints.

Ophthalmological examination revealed episcleritis. Laboratory parameters revealed anemia, raised erythrocyte sedimentation rate (60 mm/h), positive C-reactive protein, negative rheumatoid factor, and negative antinuclear and anticyclic citrullinated peptide antibodies. c- ANCA was positive while p-ANCA was negative.

Biochemical parameters were within normal limits. Urine routine and microscopic examination showed microscopic albuminuria and hematuria.

Chest radiograph and electrocardiogram were within normal limits.

Histopathology of the skin lesion revealed features of leukocytoclastic vasculitis with involvement of superficial as well as deeper blood vessels and collagen degradation [Figure 2]. Direct immunofluorescence was tested for immunoglobulin IgG, immunoglobulin IgM, immunoglobulin IgA, C₃, and fibrinogen and was found to be negative.

Figure 2.

(a) Leukocytoclastic vasculitis (blue arrow – infiltrate around superficial blood vessels, green arrow – infiltrate around deeper blood vessels, red arrow-collagen degradation) (H & E,100x), (b) Superficial vessels, and (c) Infiltrate around deeper blood vessels and (d) Karyorrhectic debris (H & E, 400x)

Diagnosis of GPA was considered in our patient based on clinical and histological findings and c-ANCA positivity.

A thorough Otorhinolaryngology and pulmonary examination was done and no significant abnormality was detected in our patient.

The patient was started on steroids at 1 mg/kg; however, since she did not respond adequately, azathioprine (2.5 mg/kg) was added, after which skin lesions started to heal partially. A month later the patient presented to the emergency department with hematemesis and severe abdominal pain. Ultrasound abdomen was grossly normal. Contrast enhanced computerized tomography abdomen showed circumferential wall thickening with luminal stenosis of the pyloric canal with mild circumferential wall thickening of the distal body of the stomach and antrum [Figure 3].

Figure 3.

Contrast-enhanced computerized tomography (CECT) abdomen showing circumferential wall thickening with luminal stenosis of the pyloric canal with mild circumferential wall thickening of distal body of stomach and antrum. (Marked with red arrow)

Upper GI endoscopy revealed severe antral gastritis with ulceration and pyloric stenosis. Biopsy of antral mucosa revealed the presence of neutrophilic infiltrates around blood vessels without any granuloma, giant cells, and malignant cells. Since the patient could not tolerate any oral medications, she was given intravenous steroids and planned for rituximab therapy.

In GPA, GI involvement is considered as a poor prognostic factor owing to life-threatening complications.[2] GI involvement is usually secondary to the systemic inflammation and is an indicator of disease severity.[3]

An array of manifestations is described in the literature with regard to GI involvement and includes erosions, edema of submucosa, hemorrhage, paralytic ileus, mesenteric ischemia, bowel obstruction, and intestinal perforation.[4] The mortality usually occurs following massive bleeding or perforation.[3]

The majority of the biopsies show nonspecific changes, thereby making it difficult to differentiate from inflammatory bowel disease.[5] Biopsy taken from the GI tract may reveal nonspecific changes as the specimen can be taken very superficially and in GPA mainly small and medium vessels are affected which typically lie in deeper submucosa.

The role of steroids in precipitating GI symptoms remains speculative. The close temporal relationship (1 month–2 years) between steroid administration and the onset of GI symptoms coupled with the fact that steroids can independently cause or worsen GI ulcers, necrosis, and perforation leads to the association. However, continuation of steroids in patients with GI disease leading to resolution was also observed,[3,4] thereby reinforcing that vasculitic etiology in GPA is largely responsible for GI manifestations. GI involvement largely occurs with 1–2 years of disease[6] or can uncommonly be the presenting feature.[4]

It is often difficult to explain the etiology of GI symptoms as similar presentation can be observed in inflammatory bowel disease, especially Crohn’s disease. In such instances, diagnosis can be considered based on immunologic test, wherein in Crohn’s disease, p-ANCA positivity is seen rarely (2–25%) and c-ANCA is positive in most GPA patients.[5] In addition, the concurrent involvement of other organ systems usually provides a clue to the diagnosis of GPA.

Masiak et al.[4] had concluded that the GI tract can predate other organ system involvement; hence, it is plausible that our patient did not have respiratory involvement at the start.

We would like to report this case to highlight the GI involvement in GPA, which is often associated with significant morbidity and mortality. A high index of suspicion with prompt therapy is often required to prevent catastrophe.

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Nil.

Conflicts of interest

There are no conflicts of interest.