- Email: [email protected]
Celiac disease in patients with HCV Genotype 1A
940
Letters to the Editor
thromboses in a child with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1997;25:533–6. 9. Hassan KO, Jenkins HR. Multiple venous thrombosis in inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1998; 27:616 –7 (letter). 10. Al-Malik H. Cerebral venous thrombosis as a complication of Crohn disease: A case report. J Pediatr Gastroenterol Nutr 2001;32:209 –11. Reprint requests and correspondence: Srinivas R. Puli, M.D., St. John’s Mercy Medical Center, Housestaff Mailbox, 615 South New Ballas Road, St. Louis, MO 63141. Received Nov. 7, 2002; accepted Nov. 18, 2002.
Acute Reversible Rhabdomyolysis During Interferon ␣2b Therapy for Hepatitis C TO THE EDITOR: A 70-yr-old man treated with interferon ␣2b (INF ␣2b) for chronic hepatitis C presented with acute rhabdomyolysis. Hepatitis C was diagnosed 6 months previously (confirmed by results of polymerase chain reaction), and liver biopsy showed moderate chronic hepatitis (histological activity index (HAI) 15, fibrosis 2) (1). Treatment with INF ␣2b (3 MIU three times wk) was started. Two weeks later, he was referred to our unit of Internal Medicine for sudden appearance of fever (38°C), weakness, and acute generalized myalgia. On admission, he denied any antecedent signs of infection, any trauma, and assumption of any other drugs except for INF. General physical examination resulted normal. Laboratory findings showed a marked increase in the concentrations of creatine kinase at 3.641 U/L (normal range 5–70 U/L) with normal concentrations of the isoform creatine kinase-MB (CK-MB), lactate dehydrogenase at 717 U/L (normal range 80 –240 U/L). Myoglobinuria was present (88 mg/L). There were no pathological alterations in concentrations of creatinine, urea nitrogen, C-reactive protein, blood cell counts, or glucose. No electrolyte abnormalities were detectable. With the diagnosis of rhabdomyolysis, INF ␣2b treatment was discontinued. The patient was treated with i.v. fluids and bicarbonate to maintain an alkaline urine output. Within 4 days, fever and myalgia disappeared, and weakness significantly improved; the creatine kinase declined to normal values (101 U/L). At the follow-up visit at 2 and 4 months, the patient was in good condition, and creatine kinase was within the normal range. Rhabdomyolysis has been reported as an unusual adverse reaction to several drugs, in particular in patients treated with statin (2). A few cases of acute rhabdomyolysis associated with INF ␣2b have been reported. Greenfield et al. described a patient 10 wk after initiation of INF ␣2b treatment starting with 5 MU three times/wk for chronic active hepatitis C (3). Reinhold et al. recently described a fatal outcome of fulminant rhabdomyolysis with multiple organ failure in a 56-yr-old man receiving adjuvant high-dose INF
AJG – Vol. 98, No. 4, 2003
␣2b (20 Mio. 1E m⫺2 daily) (4). The authors revealed that the manufacturers of INF ␣2b have received only 11 reports worldwide. Remarkably, the manifestation of muscle injury occurred when the dose of INF ␣2b was being increased in both patients described, suggesting that rhabdomyolysis represents at least a dose-dependent side effect of this drug. With respect to the previous reports, in our patient, the dosage of INF ␣2b was unaltered and significantly lower; moreover, the clinical and laboratory alterations were milder, and the recovery of the patient was quite quicker. These findings seem to confirm that muscle injury could be (if rare) a side effect of INF ␣2b, and to suggest that it may occur also at low doses. INF ␣2b discontinuation leads to a complete recovery of the disease. Measurement of creatine kinase activity could be recommended after initiation of INF ␣2b treatment and after every increasing of its dosage to precociously individualize and prevent irreversible rhabdomyolysis. Maurizio Gabrielli, M.D. Luca Santarelli, M.D. Michele Serricchio, M.D. Diego Leo, M.D. Paolo Pola, M.D. Antonio Gasbarrini, M.D. Internal Medicine and Angiology Department Catholic University of the Sacred Heart Rome, Italy
REFERENCES 1. Desmet VJ, Gerber M, Hoofnangle JH, et al. Classification of chronic hepatitis: Diagnosis, grading and staging. Hepatology 1994;19:1513–20. 2. Omar MA, Wilson JP. FDA adverse event reports on statinassociated rhabdomyolysis. Ann Pharmacother 2002;36:288 – 95. 3. Greenfield SM, Harvey RS, Thompson RP. Rhabdomyolysis after treatment with interferon alfa. BMJ 1994;309:512. 4. Reinhold U, Hartl C, Hering R, et al. Fatal rhabdomyolysis and multiple organ failure associated with adjuvant high-dose interferon alfa in malignant melanoma. Lancet 1997;349:540 –1. Reprints requests and correspondence: Antonio Gasbarrini, M.D., Internal Medicine and Angiology Department, Catholic University of the Sacred Heart, Gemelli Hospital, Largo Gemelli 8, Rome 00168, Italy. Received Nov. 8, 2002; accepted Nov. 18, 2002.
Celiac Disease in Patients With HCV Genotype 1A TO THE EDITOR: Recently, we have diagnosed celiac disease in two patients infected with hepatitis C virus (HCV) genotype 1a, and we found the paper on celiac disease authored by Volta et al. (1) interesting and relevant.
AJG – April, 2003
Letters to the Editor
Both of our patients presented with diarrhea and malabsorption with features of celiac disease on their small bowel biopsies. One patient had IgG and IgA antigliadin titers of 36 U (⬎30 strong positive) each, negative ttransglutaminase, and severe fibrosis on the liver biopsy. The second patient had an IgA antigliadin titer of 156 U, an IgG titer of 50 U, an IgA t-transglutaminase titer of ⬎200 U (0 –19), and a liver biopsy showing only mild fibrosis. On a MEDLINE search, we found five cases of celiac disease reported in association with HCV. Four patients were found in a study where HCV subjects were tested for specific markers of celiac disease to find a relationship between the two conditions (2). In another study, one patient with celiac disease was found to have HCV when investigators were looking for causes of transaminasemia in celiac disease (3). Both of our patients, however, presented with chronic diarrhea and were misdiagnosed for several years as having irritable bowel syndrome. Celiac disease can remain clinically silent or present with nonspecific symptoms leading to an erroneous diagnosis of irritable bowel syndrome (4). Clinicians should have a low threshold of screening for celiac disease in not only cholestatic liver disorders, but also among individuals infected with HCV even when only subtle GI symptoms are present. Abdul Nadir, M.D. David H. Van Thiel, M.D. Good Samaritan Regional Medical Center Phoenix, Arizona
941
Necrobiotic Nodules: A Rare Pulmonary Manifestion of Crohn’s Disease TO THE EDITOR: The pulmonary complications of inflammatory bowel disease (IBD) are protean and often underappreciated. We present a case of a patient with Crohn’s disease who developed necrobiotic pulmonary lesions. This 57-yr-old white man presented with symptoms of cough, fever, dyspnea, and orthostasis. His Crohn’s disease was predominantly colitis without extraintestinal manifestation, and he was currently in remission on mesalamine 4.8 g/day. On physical checkup, he was afebrile, with normal pulmonary and abdominal examinations. A laboratory evaluation showed a normal complete blood count and metabolic profile. A chest x-ray revealed numerous cavitary lesions throughout the lung parenchyma. A CT scan (Fig. 1) showed multiple pulmonary nodules, mainly in the peripheral lung fields, of varying sizes with the largest being 3 cm in diameter. The lesions had an illdefined border with central hypodensity noted in the larger nodules. A needle biopsy was nondiagnostic for pathogens or malignancy. The workup included negative purified protein derivative, HIV test, cryptococcal antigen, and anti-neutrophilic cytoplasmic autoantibodies. Therefore, a video-assisted thoracotomy wedge biopsy was performed. The histological evaluation (with special stains for fungi and acid-fast bacilli) with an outside pathologThis manuscript was presented in abstract form at the 45th Annual Meeting of the American College of Gastroenterology, Boston, Massachusetts, October 6 –12, 1998.
Loyola University Medical Center Maywood, Illinois
REFERENCES 1. Volta U, Rodrigo L, Granito A, et al. Celiac disease in autoimmune cholestatic liver disorders. Am J Gastroenterol 2002; 97:2610 –13. 2. Fine KD, Ogunji F, Saloum Y, et al. Celiac sprue: Another autoimmune syndrome associated with hepatitis C. Am J Gastroenterol 2001;96:138 –45. 3. Mugica F, Aranzadi M, Recasens M, et al. Adult celiac disease and hypertransaminasemia. Revista Espanola de Enfermedades Digestivas 2000;92:78 –85. 4. Farrel R, Kelly C. Current concepts: Celiac sprue. N Engl J Med 2002;346:180 –8. Reprint requests and correspondence: Abdul Nadir, M.D., Good Samaritan Regional Medical Center, 1925 East Everett Drive, Phoenix, AZ 85004. Received Nov. 11, 2002; accepted Nov. 18, 2002.
Figure 1. CT scan demonstrating multiple lesions (arrows), the largest being 3 cm with central cavitation (arrowhead).
Letters to the Editor
thromboses in a child with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1997;25:533–6. 9. Hassan KO, Jenkins HR. Multiple venous thrombosis in inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1998; 27:616 –7 (letter). 10. Al-Malik H. Cerebral venous thrombosis as a complication of Crohn disease: A case report. J Pediatr Gastroenterol Nutr 2001;32:209 –11. Reprint requests and correspondence: Srinivas R. Puli, M.D., St. John’s Mercy Medical Center, Housestaff Mailbox, 615 South New Ballas Road, St. Louis, MO 63141. Received Nov. 7, 2002; accepted Nov. 18, 2002.
Acute Reversible Rhabdomyolysis During Interferon ␣2b Therapy for Hepatitis C TO THE EDITOR: A 70-yr-old man treated with interferon ␣2b (INF ␣2b) for chronic hepatitis C presented with acute rhabdomyolysis. Hepatitis C was diagnosed 6 months previously (confirmed by results of polymerase chain reaction), and liver biopsy showed moderate chronic hepatitis (histological activity index (HAI) 15, fibrosis 2) (1). Treatment with INF ␣2b (3 MIU three times wk) was started. Two weeks later, he was referred to our unit of Internal Medicine for sudden appearance of fever (38°C), weakness, and acute generalized myalgia. On admission, he denied any antecedent signs of infection, any trauma, and assumption of any other drugs except for INF. General physical examination resulted normal. Laboratory findings showed a marked increase in the concentrations of creatine kinase at 3.641 U/L (normal range 5–70 U/L) with normal concentrations of the isoform creatine kinase-MB (CK-MB), lactate dehydrogenase at 717 U/L (normal range 80 –240 U/L). Myoglobinuria was present (88 mg/L). There were no pathological alterations in concentrations of creatinine, urea nitrogen, C-reactive protein, blood cell counts, or glucose. No electrolyte abnormalities were detectable. With the diagnosis of rhabdomyolysis, INF ␣2b treatment was discontinued. The patient was treated with i.v. fluids and bicarbonate to maintain an alkaline urine output. Within 4 days, fever and myalgia disappeared, and weakness significantly improved; the creatine kinase declined to normal values (101 U/L). At the follow-up visit at 2 and 4 months, the patient was in good condition, and creatine kinase was within the normal range. Rhabdomyolysis has been reported as an unusual adverse reaction to several drugs, in particular in patients treated with statin (2). A few cases of acute rhabdomyolysis associated with INF ␣2b have been reported. Greenfield et al. described a patient 10 wk after initiation of INF ␣2b treatment starting with 5 MU three times/wk for chronic active hepatitis C (3). Reinhold et al. recently described a fatal outcome of fulminant rhabdomyolysis with multiple organ failure in a 56-yr-old man receiving adjuvant high-dose INF
AJG – Vol. 98, No. 4, 2003
␣2b (20 Mio. 1E m⫺2 daily) (4). The authors revealed that the manufacturers of INF ␣2b have received only 11 reports worldwide. Remarkably, the manifestation of muscle injury occurred when the dose of INF ␣2b was being increased in both patients described, suggesting that rhabdomyolysis represents at least a dose-dependent side effect of this drug. With respect to the previous reports, in our patient, the dosage of INF ␣2b was unaltered and significantly lower; moreover, the clinical and laboratory alterations were milder, and the recovery of the patient was quite quicker. These findings seem to confirm that muscle injury could be (if rare) a side effect of INF ␣2b, and to suggest that it may occur also at low doses. INF ␣2b discontinuation leads to a complete recovery of the disease. Measurement of creatine kinase activity could be recommended after initiation of INF ␣2b treatment and after every increasing of its dosage to precociously individualize and prevent irreversible rhabdomyolysis. Maurizio Gabrielli, M.D. Luca Santarelli, M.D. Michele Serricchio, M.D. Diego Leo, M.D. Paolo Pola, M.D. Antonio Gasbarrini, M.D. Internal Medicine and Angiology Department Catholic University of the Sacred Heart Rome, Italy
REFERENCES 1. Desmet VJ, Gerber M, Hoofnangle JH, et al. Classification of chronic hepatitis: Diagnosis, grading and staging. Hepatology 1994;19:1513–20. 2. Omar MA, Wilson JP. FDA adverse event reports on statinassociated rhabdomyolysis. Ann Pharmacother 2002;36:288 – 95. 3. Greenfield SM, Harvey RS, Thompson RP. Rhabdomyolysis after treatment with interferon alfa. BMJ 1994;309:512. 4. Reinhold U, Hartl C, Hering R, et al. Fatal rhabdomyolysis and multiple organ failure associated with adjuvant high-dose interferon alfa in malignant melanoma. Lancet 1997;349:540 –1. Reprints requests and correspondence: Antonio Gasbarrini, M.D., Internal Medicine and Angiology Department, Catholic University of the Sacred Heart, Gemelli Hospital, Largo Gemelli 8, Rome 00168, Italy. Received Nov. 8, 2002; accepted Nov. 18, 2002.
Celiac Disease in Patients With HCV Genotype 1A TO THE EDITOR: Recently, we have diagnosed celiac disease in two patients infected with hepatitis C virus (HCV) genotype 1a, and we found the paper on celiac disease authored by Volta et al. (1) interesting and relevant.
AJG – April, 2003
Letters to the Editor
Both of our patients presented with diarrhea and malabsorption with features of celiac disease on their small bowel biopsies. One patient had IgG and IgA antigliadin titers of 36 U (⬎30 strong positive) each, negative ttransglutaminase, and severe fibrosis on the liver biopsy. The second patient had an IgA antigliadin titer of 156 U, an IgG titer of 50 U, an IgA t-transglutaminase titer of ⬎200 U (0 –19), and a liver biopsy showing only mild fibrosis. On a MEDLINE search, we found five cases of celiac disease reported in association with HCV. Four patients were found in a study where HCV subjects were tested for specific markers of celiac disease to find a relationship between the two conditions (2). In another study, one patient with celiac disease was found to have HCV when investigators were looking for causes of transaminasemia in celiac disease (3). Both of our patients, however, presented with chronic diarrhea and were misdiagnosed for several years as having irritable bowel syndrome. Celiac disease can remain clinically silent or present with nonspecific symptoms leading to an erroneous diagnosis of irritable bowel syndrome (4). Clinicians should have a low threshold of screening for celiac disease in not only cholestatic liver disorders, but also among individuals infected with HCV even when only subtle GI symptoms are present. Abdul Nadir, M.D. David H. Van Thiel, M.D. Good Samaritan Regional Medical Center Phoenix, Arizona
941
Necrobiotic Nodules: A Rare Pulmonary Manifestion of Crohn’s Disease TO THE EDITOR: The pulmonary complications of inflammatory bowel disease (IBD) are protean and often underappreciated. We present a case of a patient with Crohn’s disease who developed necrobiotic pulmonary lesions. This 57-yr-old white man presented with symptoms of cough, fever, dyspnea, and orthostasis. His Crohn’s disease was predominantly colitis without extraintestinal manifestation, and he was currently in remission on mesalamine 4.8 g/day. On physical checkup, he was afebrile, with normal pulmonary and abdominal examinations. A laboratory evaluation showed a normal complete blood count and metabolic profile. A chest x-ray revealed numerous cavitary lesions throughout the lung parenchyma. A CT scan (Fig. 1) showed multiple pulmonary nodules, mainly in the peripheral lung fields, of varying sizes with the largest being 3 cm in diameter. The lesions had an illdefined border with central hypodensity noted in the larger nodules. A needle biopsy was nondiagnostic for pathogens or malignancy. The workup included negative purified protein derivative, HIV test, cryptococcal antigen, and anti-neutrophilic cytoplasmic autoantibodies. Therefore, a video-assisted thoracotomy wedge biopsy was performed. The histological evaluation (with special stains for fungi and acid-fast bacilli) with an outside pathologThis manuscript was presented in abstract form at the 45th Annual Meeting of the American College of Gastroenterology, Boston, Massachusetts, October 6 –12, 1998.
Loyola University Medical Center Maywood, Illinois
REFERENCES 1. Volta U, Rodrigo L, Granito A, et al. Celiac disease in autoimmune cholestatic liver disorders. Am J Gastroenterol 2002; 97:2610 –13. 2. Fine KD, Ogunji F, Saloum Y, et al. Celiac sprue: Another autoimmune syndrome associated with hepatitis C. Am J Gastroenterol 2001;96:138 –45. 3. Mugica F, Aranzadi M, Recasens M, et al. Adult celiac disease and hypertransaminasemia. Revista Espanola de Enfermedades Digestivas 2000;92:78 –85. 4. Farrel R, Kelly C. Current concepts: Celiac sprue. N Engl J Med 2002;346:180 –8. Reprint requests and correspondence: Abdul Nadir, M.D., Good Samaritan Regional Medical Center, 1925 East Everett Drive, Phoenix, AZ 85004. Received Nov. 11, 2002; accepted Nov. 18, 2002.
Figure 1. CT scan demonstrating multiple lesions (arrows), the largest being 3 cm with central cavitation (arrowhead).