A young woman with microcytic
anemia and hypertransaminasemia
Luca Arcaini, Paola Cerani, Angela Lorenzi, and Mario
Lazzarino
Correspondence: Luca Arcaini, MD, Division of of Hematology,
University of Pavia, IRCCS Policlinico S. Matteo, 27100 - Pavia,
Italy. Phone: international +39-0382-503596 - Fax international
+39-0382-502250 . Email: larcaini@hotmail.com
We report on a 31-year-old woman who was referred to our Division
for microcytic anaemia, mild hypertransaminasemia and IgA
monoclonal component.
She had neither a history of pharmacological assumption, alcohol and drug abuse nor relevant diseases, apart from except the presence of mild anaemia with MCV of near 80 fl since 1994. She had menarche when she was sixteen and had two pre-termine pregnancies: one child died in neonatal period, while the other one is a healthy 2 year-old boy. Three months before referral, blood laboratory tests showed moderate microcytic anaemia and hypergammaglobulinemia with presence of IgA monoclonal component and mild elevation in serum transaminases with normal findings on liver echotomography. Physical examination, conducted at the time of her referral to our Division, showed only pallor of skin and mucosas. The patient did not report any symptom. We confirmed the presence of microcytic anaemia and the elevation of transaminases while we found high polyclonal IgA and IgM titers without serum and urine monoclonal component. The laboratory evaluation performed on first referral is reported in Table 1.
Sideropenia, in absence of menstrual irregularities and occult blood loss, and concomitant folate deficiency, in absence of alcohol abuse and dietary restriction, were likely due to malabsorption. Therefore we screened patient for coeliac disease and milk protein intolerance. In fact, we found negativity for the latter and for anti-endomisium antibodies (EMA), while IgA to gliadin were > 100 mg/L and IgG to gliadin were 47.9 mg/L (normal values: IgA < 3 mg/L, IgG < 18/mg/L). A subsequent fiberoptic upper-gastrointestinal-tract endoscopy showed hypotrophy of duodenal mucosa and the microscopical examination of biopsies samples revealed complete villous atrophy, interstitial and intraepithelial lymphocytic infiltrate and crypt hyperplasia. A diagnosis of coeliac disease was formulated. Liver abnormalities in our patient were not explained by virologic, toxic, metabolic or pharmacological causes. Since association between coeliac disease and primary biliary cirrhosis1 or primary sclerosing cholangitis2 is reported in literature, we searched for antibodies directed against smooth muscle and mithocondria, but this test resulted negative. Finally we ruled out autoimmune hepatitis (anti-dsDNA antibodies, ANA, anti-liver-kidney microsomes, anti-liver cytosol were negative), deficiency of a 1 antitripsine and Wilson's disease (a1 antitripsine and ceruloplasmine were in normal range) and seronegative HCV hepatitis (PCR test for circulating HCV-RNA was negative). In this case, the exclusion of common and rare hepatic diseases allowed us to consider the hepatic injury strictly connected with gluten-intolerance, as reported in literature since 1977.3 In fact, after three months of gluten-free diet, beyond anaemia resolution, there was a complete recovery of AST and ALT levels and after six months the duodenal biopsy showed normal findings. On the basis of the literature data, hypetransaminasemia occurs in up to 40% of patients affected with coeliac disease4 while gluten intolerance is diagnosed in 5-10% of cryptogenic liver abnormalities. Pathogenic mechanism of liver injury is not clear, but metabolic alteration, induced by long-standing malnutrition or alterated permeability and consequent damage by toxins or antigens circulating in portal system, seems to play a role.5 The histologic pattern is not specific with a picture of mild periportal inflammation and mild fatty infiltration that usually recovers with withdrawal of gluten.3,6
In last decade a growing awareness of coeliac disease as a cause of anaemia has been established.7 In a recent paper by Hin et al.8 iron-deficiency anaemia is the presentation hallmark in about 50% of individuals affected with adult coeliac disease, whereas about 9% of a population of microcytic anemic patients have subclinical coeliac disease. However, in hematological journals it is rarely reported that iron deficient anaemia could be justified by coeliac disease.9 Only recently, a large investigation on blood volunteers pointed out that, among asymptomatic iron-deficient anaemic subjects, nearly 6% were affected by sub-clinical coeliac disease.10 Our case showed some peculiarities: EMA negativity, absence of gastrointestinal symptoms and, particularly, mild elevation of transaminases. Therefore, coeliac disease can be the explanation of polymorphic clinical pictures, as in our case. For this reason hematologists in clinical practice should perform a screening for coeliac disease, both with antiendomysial and antigliadin antibody testing, in all patients showing microcytic anaemia and liver cryptogenic alteration, even in absence of gastrointestinal symptoms.
