Original Article
α1-Antitrypsin Deficiency and Inflammatory Bowel Diseases

https://doi.org/10.4065/75.5.450Get rights and content

Objective

To evaluate a possible etiologic role of a α-antitrypsin deficiency (α1AD), most frequently caused by a Z allele mutation, in ulcerative colitis (UC) and Crohn disease (CD).

Patients and Methods

This retrospective study included 10 patients diagnosed with and/or treated for inflammatory bowel disease (IBD) between 1976 and 1997 and identified from the Mayo Clinic Medical Index System. All 10 patients had either α1 AD and CD or α1AD and UC. The α1-antitrypsin (α1AT)types and levels were determined with isoelectric focusing testing. The allele types, representing genotypes, were designated PiZZ (or ZZ) for homozygotes and PiMZ (or MZ) for heterozygotes.

Results

Seven patients had UC: 4 were genotype ZZ and 3 MZ. Four of these 7 patients had emphysema, 2 had asthma, and 1 had chronic bronchitis. Five were cigarette smokers, but only 1 had smoked coincident with activity of her UC. Two of the UC patients never smoked, and 1 of these 2 had asthma. Three of the 10 patients had CD, 2 genotype ZZ and 1 MZ. Two of the 3 patients were longterm cigarette smokers, and both had emphysema. Nine of the 10 patients with UC and α1 AD required surgery.

Conclusions

The need for surgery in patients with UC and α1-AD may point to a unique phenotypic subgroup of patients with α1AD and severe UC. Further studies are required to substantiate the etiologic role of α1AD in IBD. Our observations, if confirmed by future studies, suggest that in patients with both IBD and chronic obstructive pulmonary disease, α1AD testing should be considered.

Section snippets

PATIENTS AND METHODS

All 10 patients were diagnosed with and/or treated for IBD at Mayo Clinic Rochester. Cases were identified using the Hospital Adaptation of International Classification of Diseases (H-ICDA) codes19 563.0 for CD and 563.1 for UC. Codes 02739.11.0 and 02739.11.1 for α1AD are specific to the Mayo modification of the H-ICDA. Only the patients who had either α1AD and CD or α1AD and UC listed in the Mayo Clinic Medical Index System between 1976 and 1997 are described in this report. The diagnosis of

RESULTS

Table 1 summarizes the pertinent clinical data on the 10 patients identified in this study. Age and calendar year of each important diagnosis and tobacco smoking history are also provided. Seven patients had UC: 4 had the PiZZ allele (cases 1–4), and 3 had the PiMZ allele (cases 5–7). Four of the 7 patients with UC had emphysema, 2 had asthma, and 1 had chronic bronchitis. Five of the 7 were long-term cigarette smokers, and 2 had never smoked. One of the never smokers had asthma (case 7), and

DISCUSSION

Although an elevated fecal level of α1AT has been used as the protein clearance marker in IBD to indicate disease activity,23, 24 UC or CD has not been documented as part of α1AD sequelae. To our knowledge, this is the largest case series in which α1AD is described in association with UC or CD. There are 2 case reports in the literature: the first described a patient with α1AD and CD, in which the diagnosis of α1AD was based on the serum α1AT level and liver biopsy findings.16 The genotype of

ACKNOWLEDGMENTS

The authors wish to thank the secretarial support from Marilyn M. Goodman and the retrieval of cases from Mayo Clinic Medical Index System by James R. Wentz.

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