Advertisement
Mayo Clinic Proceedings Home

Cardiomyopathy Associated With Celiac Disease

      Celiac disease or celiac sprue is predominantly a disease of the small intestine characterized by chronic malabsorption in genetically susceptible individuals who ingest grains containing gluten, such as wheat, barley, and rye. Although previously believed to be uncommon, celiac disease may be present in up to 1% of the general population. Celiac disease is associated frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, and various connective tissue disorders but is rarely associated with cardiomyopathy. We describe a patient with celiac disease associated with cardiomyopathy whose cardiac function improved substantially after treatment with a gluten-free diet. Cardiomyopathy associated with celiac disease is a serious and potentially lethal condition. However, with early diagnosis and treatment with a gluten-free diet, cardiomyopathy in patients with celiac disease may be completely reversible.
      Celiac disease or celiac sprue is characterized by chronic malabsorption in susceptible individuals who ingest grains containing gluten, such as wheat, barley, and rye. Until recently, celiac disease was believed to be relatively uncommon. However, a recent report from Finland estimates its prevalence at 1% in the general population.
      • Maki M
      • Mustalahti K
      • Kokkonen J
      • et al.
      Prevalence of celiac disease among children in Finland.
      Celiac disease is associated frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency,
      • Meini A
      • Pillan NM
      • Villanacci V
      • Monafo V
      • Ugazio AG
      • Plebani A
      Prevalence and diagnosis of celiac disease in IgA-deficient children.
      thyroid disorders,
      • Counsell CE
      • Taha A
      • Ruddell WS
      Coeliac disease and autoimmune thyroid disease.
      diabetes mellitus,
      • Cronin CC
      • Feighery A
      • Ferriss JB
      • Liddy C
      • Shanahan F
      • Feighery C
      High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus.
      • Talal AH
      • Murray JA
      • Goeken JA
      • Sivitz WI
      Celiac disease in an adult population with insulin-dependent diabetes mellitus: use of endomysial antibody testing.
      and various connective tissue disorders.
      • Rustgi AK
      • Peppercorn MA
      Gluten-sensitive enteropathy and systemic lupus erythematosus.
      • Komatireddy GR
      • Marshall JB
      • Aqel R
      • Spollen LE
      • Sharp GC
      Association of systemic lupus erythematosus and gluten enteropathy.
      • Collin P
      • Reunala T
      • Pukkala E
      • Laippala P
      • Keyrilainen O
      • Pasternack A
      Coeliac disease—associated disorders and survival.
      Cardiomyopathy associated with celiac disease is reported infrequently. We describe a case of cardiomyopathy in a patient with celiac disease who had neither gastrointestinal symptoms nor manifestations of malabsorption and whose cardiac function improved substantially after treatment with a gluten-free diet.

      REPORT OF A CASE

      A 70-year-old man with chronic atrial fibrillation and left ventricular dysfunction presumed to be secondary to coronary artery disease was evaluated for 4 episodes of intermittent, nonexertional chest pain during the previous 3 months, each episode lasting approximately 5 minutes. He had no associated symptoms of dyspnea, diaphoresis, or palpitations. Dermatitis herpetiformis had been diagnosed 20 years previously; a gluten-free diet was advised, and dapsone was prescribed. The patient continued to take dapsone but for the previous 10 years had been noncompliant with a gluten-free diet. The patient had no history of alcohol use, diarrhea, weight loss, or fever but had experienced drenching night sweats for approximately 4 years.
      Results of physical examination revealed a blood pressure of 130/80 mm Hg and a heart rate of 100 beats/min. Cardiac rhythm was irregular with a 1/6 holosystolic murmur audible at the apex. An erythematous, papulovesicular rash was noted on the buttocks bilaterally, consistent with dermatitis herpetiformis. Findings were normal for the rest of the physical examination and for complete blood cell counts, serum chemistries, serum ferritin level, and thyroid function tests. Chest radiography revealed cardiomegaly, and echocardiography showed global hypokinesis with a left ventricular ejection fraction of 45%. Coronary angiography revealed minimal coronary atherosclerosis. Abdominal fat pad aspirate was negative for amyloid deposition. Tissue transglutaminase antibody was positive at 256 U (reference range, <20 U). Upper gastrointestinal endoscopy revealed scalloped duodenal folds, and results of a histopathologic examination revealed partial villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. Computed tomography of the abdomen was unremarkable except for nonspecific lymphadenopathy in the porta hepatis.
      Celiac disease with probable celiac disease–associated cardiomyopathy was diagnosed, and a strict gluten-free diet was initiated. The patient had been taking losartan before the diagnosis of celiac disease–associated cardiomyopathy and continued to take this drug. On evaluation 10 months later, the patient had gained 8.6 kg, the night sweats had resolved, and there were no further episodes of chest pain. The abdominal lymphadenopathy had regressed, and transthoracic echocardiography showed an ejection fraction of 65% with no wall motion abnormalities.

      DISCUSSION

      Celiac disease is predominantly a disease of the small intestine that develops in genetically susceptible individuals after dietary exposure to grains containing gluten. Ingestion of gluten results in inflammation of the intestinal mucosa along with hyperplasia of the crypts and atrophy of the villi of the small intestine. The inflammatory response is believed to be mediated by immune mechanisms. The classic symptom of the disease is malabsorption manifesting as diarrhea, iron deficiency anemia, and weight loss. Other manifestations include osteomalacia, coagulopathy, and peripheral neuropathy. A gluten-free diet usually results in complete resolution of the symptoms and correction of the metabolic abnormalities.
      An association between celiac disease and cardiomyopathy was reported recently. One study of 52 patients reported an increased prevalence of celiac disease (5.8%) in patients with dilated cardiomyopathy.
      • Curione M
      • Barbato M
      • De Biase L
      • Viola F
      • Lo Russo L
      • Cardi E
      Prevalence of coeliac disease in idiopathic dilated cardiomyopathy [letter].
      In another study, Prati et al
      • Prati D
      • Bardella MT
      • Peracchi M
      • Porretti L
      • Scalamogna M
      • Conte D
      Antiendomysial antibodies in patients with end-stage heart failure [letter].
      found that the prevalence of celiac disease in patients with dilated cardiomyopathy was 2.2% compared with 0.35% in controls.
      On review of English literature published since 1966, we found only 14 other cases of cardiomyopathy associated with celiac disease (Table 1
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      ). Only patients who had both serologic evidence and biopsy findings consistent with celiac disease were included in this review. Of the 15 patients reviewed, including our patient, only 4 (27%) had a history of typical gastrointestinal symptoms of celiac sprue.
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      Iron deficiency anemia, the most common manifestation of celiac disease in these patients, was present in 11 patients (73%).
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      Our patient had no gastrointestinal symptoms or iron deficiency anemia. Eleven patients (73%) presented with congestive heart failure,
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      and 4 (27%) presented with ventricular arrhythmias with normal ejection fraction.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      Nine patients (60%) had biopsy-proven myocarditis,
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      whereas the remaining 6 (40%) were diagnosed as having dilated cardiomyopathy.
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      Table 1Literature Review (1966-2003) of Celiac Disease–Associated Cardiomyopathy
      CHF = congestive heart failure; EF = ejection fraction; LC = Lown class; VA = ventricular arrhythmia.
      ReferencePatient age (y)/sexClinical presentationDiagnosisTreatmentOutcome
      Patients with improved cardiac parameters also had improvement in their anemia and gastrointestinal symptoms.
      Makhdoom & Randall,
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      2000
      49/FCHF (EF 30%); anemiaDilated cardiomyopathyGluten-free dietEF 65%
      Chuaqui et al,
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      1986
      34/MCHF; diarrhea, weight lossDilated cardiomyopathyGluten-free dietDied
      Curione,
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      2002
      40/MCHF (EF 38%); diarrhea, anemiaDilated cardiomyopathyGluten-free dietEF 42%
      32/MCHF (EF 25%); diarrhea, anemiaDilated cardiomyopathyGluten-free dietEF 30%
      26/MCHF (EF 36%); diarrhea, anemiaDilated cardiomyopathyGluten-free diet
      Patient was noncompliant with the prescribed diet.
      EF 30%
      Frustaci et al,
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      2002
      14/FVA (LC III); anemiaLymphocytic myocarditisGluten-free dietLC I
      36/MCHF (EF 27%); anemiaLymphocytic myocarditisGluten-free diet and immunosuppressionEF 48%
      16/FCHF (EF 36%); anemiaLymphocytic myocarditisGluten-free diet and immunosuppressionEF 54%
      38/FVA (LC IVa); anemiaLymphocytic myocarditisGluten-free dietLC I
      32/MCHF (EF 17%); anemiaLymphocytic myocarditisGluten-free diet and immunosuppressionEF 46%
      16/FVA (LC III); anemiaLymphocytic myocarditisGluten-free dietLC I
      35/FVA (LC IVa); anemiaLymphocytic myocarditisGluten-free dietLC I
      22/FCHF (EF 21%); anemiaGiant-cell myocarditisGluten-free diet and immunosuppressionEF 56%
      24/FCHF (EF 32%); anemiaLymphocytic myocarditisGluten-free diet and immunosuppressionEF 54%
      Current study70/MCHF (EF 40%); dermatitis herpetiformisDilated cardiomyopathyGluten-free dietEF 65%
      * CHF = congestive heart failure; EF = ejection fraction; LC = Lown class; VA = ventricular arrhythmia.
      Patients with improved cardiac parameters also had improvement in their anemia and gastrointestinal symptoms.
      Patient was noncompliant with the prescribed diet.
      Several mechanisms have been proposed for the development of cardiomyopathy in celiac sprue. Chronic malabsorption, common in celiac disease, may lead to cardiomyopathy secondary to nutritional deficiencies.
      • Chimenti C
      • Pieroni M
      • Maseri A
      • Frustaci A
      Dilated cardiomyopathy and celiac disease [reply].
      Abnormalities of intestinal permeability in patients with celiac disease may lead to increased systemic absorption of various luminal antigens or infectious agents that may cause myocardial damage through immune-mediated mechanisms.
      • van Elburg RM
      • Uil JJ
      • Mulder CJ
      • Heymans HS
      Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.
      • DeMeo MT
      • Mutlu EA
      • Keshavarzian A
      • Tobin MC
      Intestinal permeation and gastrointestinal disease.
      • Hall EJ
      • Batt RM
      Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs.
      Finally, myocardial injury may be secondary to an immune response directed against an antigen present in both the myocardium and the small intestine.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      • Chimenti C
      • Pieroni M
      • Maseri A
      • Frustaci A
      Dilated cardiomyopathy and celiac disease [reply].
      • Curione M
      Dilated cardiomyopathy and celiac disease [letter].
      In our review, all 9 patients with myocarditis had detectable anti-cardiac antibodies supporting an immune-mediated mechanism.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      A recent study suggests that celiac disease is associated with cardiomyopathy rather than being a cause of cardiomyopathy because celiac disease did not cosegregate with cardiomyopathy on HLA testing.
      • Not T
      • Faleschini E
      • Tommasini A
      • et al.
      Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives.
      Of the patients reviewed, 10 (67%) were treated with a strict gluten-free diet alone.
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      The remaining 5 patients (33%) were treated with the immunosuppressive agents azathioprine and prednisone in addition to dietary restrictions.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      Of the patients treated with a gluten-free diet alone, 1 patient was noncompliant and presented with worsening left ventricular function at 26-month followup.
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      Another patient died secondary to intractable heart failure 1 month after presentation.
      • Chuaqui B
      • Garrido J
      • Casanegra P
      Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
      The remaining 8 patients had substantial improvement in their ejection fraction and suppression of ventricular arrhythmias.
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      • Curione M
      • Barbato M
      • Viola F
      • Francia P
      • De Biase L
      • Cucchiara S
      Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      In 1 patient, noncompliance with a gluten-free diet 16 months after resolution of symptoms resulted in relapse of her enteropathy and cardiomyopathy with significant worsening of her ejection fraction.
      • Makhdoom ZA
      • Randall NW
      Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
      All patients who were treated with a combination of immunosuppression and gluten-free diet had improvement in their left ventricular function at 12-month follow-up.
      • Frustaci A
      • Cuoco L
      • Chimenti C
      • et al.
      Celiac disease associated with autoimmune myocarditis.
      Our case highlights several important points about celiac disease and associated conditions. Celiac disease in adults is often asymptomatic or presents with extremely few symptoms. A high degree of clinical suspicion is required to make a prompt and correct diagnosis. Cardiomyopathy associated with celiac disease is a serious and potentially lethal condition. However, if diagnosed early, cardiomyopathy may be completely reversible with initiation of a gluten-free diet. A careful medical history should be obtained to elicit gastrointestinal symptoms, and the presence of iron deficiency anemia should be investigated in patients who present with dilated cardiomyopathy or myocarditis in the absence of known etiologies. Such patients also should be screened for celiac disease with serologic tests such as tissue transglutaminase antibody.

      REFERENCES

        • Maki M
        • Mustalahti K
        • Kokkonen J
        • et al.
        Prevalence of celiac disease among children in Finland.
        N Engl J Med. 2003; 348: 2517-2524
        • Meini A
        • Pillan NM
        • Villanacci V
        • Monafo V
        • Ugazio AG
        • Plebani A
        Prevalence and diagnosis of celiac disease in IgA-deficient children.
        Ann Allergy Asthma Immunol. 1996; 77: 333-336
        • Counsell CE
        • Taha A
        • Ruddell WS
        Coeliac disease and autoimmune thyroid disease.
        Gut. 1994; 35: 844-846
        • Cronin CC
        • Feighery A
        • Ferriss JB
        • Liddy C
        • Shanahan F
        • Feighery C
        High prevalence of celiac disease among patients with insulin-dependent (type I) diabetes mellitus.
        Am J Gastroenterol. 1997; 92: 2210-2212
        • Talal AH
        • Murray JA
        • Goeken JA
        • Sivitz WI
        Celiac disease in an adult population with insulin-dependent diabetes mellitus: use of endomysial antibody testing.
        Am J Gastroenterol. 1997; 92: 1280-1284
        • Rustgi AK
        • Peppercorn MA
        Gluten-sensitive enteropathy and systemic lupus erythematosus.
        Arch Intern Med. 1988; 148: 1583-1584
        • Komatireddy GR
        • Marshall JB
        • Aqel R
        • Spollen LE
        • Sharp GC
        Association of systemic lupus erythematosus and gluten enteropathy.
        South Med J. 1995; 88: 673-676
        • Collin P
        • Reunala T
        • Pukkala E
        • Laippala P
        • Keyrilainen O
        • Pasternack A
        Coeliac disease—associated disorders and survival.
        Gut. 1994; 35: 1215-1218
        • Curione M
        • Barbato M
        • De Biase L
        • Viola F
        • Lo Russo L
        • Cardi E
        Prevalence of coeliac disease in idiopathic dilated cardiomyopathy [letter].
        Lancet. 1999; 354: 222-223
        • Prati D
        • Bardella MT
        • Peracchi M
        • Porretti L
        • Scalamogna M
        • Conte D
        Antiendomysial antibodies in patients with end-stage heart failure [letter].
        Am J Gastroenterol. 2002; 97: 218-219
        • Makhdoom ZA
        • Randall NW
        Dilated cardiomyopathy due to anti-cardiolipin syndrome in association with celiac sprue [letter].
        J Clin Gastroenterol. 2000; 31: 91-92
        • Chuaqui B
        • Garrido J
        • Casanegra P
        Actin-deficient cardiomyopathy coexisting with celiac disease: a chance association?.
        Pathol Res Pract. 1986; 181: 604-614
        • Curione M
        • Barbato M
        • Viola F
        • Francia P
        • De Biase L
        • Cucchiara S
        Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance.
        Dig Liver Dis. 2002; 34: 866-869
        • Frustaci A
        • Cuoco L
        • Chimenti C
        • et al.
        Celiac disease associated with autoimmune myocarditis.
        Circulation. 2002; 105: 2611-2618
        • Chimenti C
        • Pieroni M
        • Maseri A
        • Frustaci A
        Dilated cardiomyopathy and celiac disease [reply].
        Ital Heart J. 2002; 3: 385
        • van Elburg RM
        • Uil JJ
        • Mulder CJ
        • Heymans HS
        Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.
        Gut. 1993; 34: 354-357
        • DeMeo MT
        • Mutlu EA
        • Keshavarzian A
        • Tobin MC
        Intestinal permeation and gastrointestinal disease.
        J Clin Gastroenterol. 2002; 34: 385-396
        • Hall EJ
        • Batt RM
        Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs.
        Gut. 1991; 32: 749-753
        • Curione M
        Dilated cardiomyopathy and celiac disease [letter].
        Ital Heart J. 2002; 3: 384-385
        • Not T
        • Faleschini E
        • Tommasini A
        • et al.
        Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives.
        Eur Heart J. 2003; 24: 1455-1461