Demographics and environmental factors in a Wegener's granulomatosis cluster

Wegener's granulomatosis is a multiorgan systemic disease of unknown aetiology, characterised by granulomatous inflammation and vasculitis in small or medium‐sized blood vessels. Available evidence suggests a role for genetics, microbial pathogens and environmental exposures in its aetiology.¹ Agents including silica,² hydrocarbons,³ pesticides,⁴ fumes⁴ and farming⁵ have been implicated. We describe the demographic details and environmental exposures of a cluster of patients with Wegener's granulomatosis cases diagnosed in Norfolk, UK. Cluster analysis enables identification of common environmental exposures that may be temporally and spatially related to disease features.

We identified eight patients who were diagnosed with Wegener's granulomatosis between February 2005 and February 2006. All patients fulfilled the 1990 American College of Rheumatology criteria for Wegener's granulomatosis. They were referred to the Norfolk and Norwich University Hospital, Norfolk, UK, which has a catchment area of about 750 000 people. The annual incidence of Wegener's granulomatosis in Norfolk is estimated to be 8.5/million/year in a previous study.⁶ A validated questionnaire on environmental exposures, used in a previous study in Norfolk,⁵ was administered by an interviewer to all patients.

Table 1 shows the demographic details including estimated age at first symptom (index age) and organ involvement. Two patients were diagnosed with localised Wegener's granulomatosis, as defined by the European Vasculitis Study Group,⁷ with involvement of only the upper respiratory tract and negative for classic antineutrophil cytoplasmic antibody (cANCA). The remaining patients were positive for cANCA and had renal involvement (generalised Wegener's granulomatosis). The estimated date of first symptoms (index date) was between 2003 and 2004, and all patients were residents of Norfolk at least a year before.

Table 1 Demographics and organ involvement in patients with Wegener's granulomatosis.

Sex	Index age (year)	cANCA	Nose/ears	Pulmonary	Renal
Female*	38	–	+	–	–
Male*	52	–	+	–	–
Male	41	+	+	–	+
Female	38	+	+	+	+
Male	47	+	+	+	+
Female	66	+	+	+	+
Male	73	+	+	+	+
Male	47	+	+	+	+

+, positive involvement; −, no involvement; cANCA, classic antineutrophil cytoplasmic antibody. Status confirmed by both immunofluorescence microscopy and ELISA.

*Localised Wegener's granulomatosis.

High farming activity was reported by five patients in the index year, with two patients reporting exposures outside Norfolk, making it the most frequently reported agent. Four patients reported close contact with animals, with three reporting specific exposure to farm animals. Four patients also reported frequent gardening activities. High exposures to dust, construction work and a history of allergy were reported by three patients each. No common factors were identified in occupation, hobbies, infections, and solvent or drug exposure in the index year.

Table 2 shows the association between environmental agents, organ involvement and cANCA status. All patients with localised Wegener's granulomatosis reported no exposure to farming activities in the index year. Five of the remaining six patients with generalised Wegener's granulomatosis reported high exposure to farming.

Table 2 Association of environmental agents according to organ involvement and antineutrophil cytoplasmic antibody status.

Item	Farm (n)	High dust (n)	High solvent (n)	Allergy (n)	Gardening (n)	Animals (n)
Renal*	5	2	1	2	3	3
No renal	0	1	0	1	1	1
Pulmonary†	5	2	1	2	4	4
No pulmonary	0	1	0	0	0	0
cANCA	5	2	1	2	3	3
No cANCA	0	1	0	1	1	1

cANCA, circulating anti‐neutrophil cytoplasmic antibody.*Haematuria, increased creatinine level or renal biopsy findings, consistent with vasculitis.

†Haemoptysis or chest radiography findings, consistent with vasculitis.

This concise report on a cluster of Wegener's granulomatosis further supports its association with farming.⁵ This study also shows a difference in environmental exposure between localised and generalised Wegener's granulomatosis in a disease cluster, which has not been reported previously. Although it is well known that only 60% of patients with localised Wegener's granulomatosis are positive for cANCA,⁸ it is interesting that none of our patients reported exposure to farming in our report. Statistical analysis could not be performed in our study owing to the small number of cases in both groups. Nevertheless, we hypothesise that localised and generalised forms of Wegener's granulomatosis may be explained by different environmental exposures, and warrant further epidemiological studies.