Inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura. (Case Report).

Abstract: We report an unusual case of a 51-year-old woman with inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura. We propose that the presence of all three disorders together suggests that they may share an interrelated immune mechanism.

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Inclusion body myositis (IBM) is an inflammatory myoplathy characterized by progressive muscle weakness. Unlike the other inflammatory myopathies, IBM often involves the distal musculature and tends to be steroid nonresponsive. (1) Celiac sprue (CS) is a mucosal disorder of the small intestine. It may be asymptomatic or manifested by either intestinal malabsorptive symptoms or extraintestinal symptoms. (2) Idiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count, normally functioning bone marrow, and the absence of other disorders that may account for thrombocytopenia. Patients with ITP may be asymptomatic or may present with easy bruising, menorrhagia, or expistaxis. (3) The cause of CS appears to be autoimmune, whereas the cause of IBM remains undefined. (1,4) ITP is known to have an autoimmune cause. (5) Seven adult cases of CS occurring in association with ITP (6-11) two cases of IBM with ITP, (12,13) and one case of IBM occurring with CS (14) have been reported previously. We re port a case of IBM, CS, and ITP occurring in a middle-aged woman.

Discussion

We found several previous reports of concurrent IBM with CS, (14) IBM with ITP, (12,13) and CS with ITP. (6-11) However, we know of no other reported case of all three disorders occurring in the same patient. The coexistence of IBM, CS, and ITP in this patient adds to the already existing evidence that these disorders may share a common pathogenesis, probably an immune one.

Chronic ITP is known to be an autoimmune disorder. In affected patients, platelets are sensitized with antiplatelet antibodies and then destroyed by the reticuloendothelial system. Several studies have now shown that these autoantibodies are directed against platelet glycoprotein (GP) complexes, GP IIb/IIIa or GP Ib/IX. (5)

Likewise, in CS, autoantibodies are thought to play a role. It is now thought that in generically susceptible individuals, gluten peptides trigger the production of autoantibodies that are directed against tissue transglutaminase, an enzyme now identified as the primary, if not sole, endomysial autoantigen. (4)

Although the pathogenesis of IBM is less clear, much evidence supports an immune mechanism. First, IBM is frequently associated with other systemic autoimmune disorders. (1,15) In addition, there is evidence of an immune-triggered myotoxicity that appears to be antigen-directed and mediated by cytotoxic T cells. A number of autoantibodies have also been identified in patients with IBM, but they are not specific to this disorder and their role in its pathogenesis remains undefined. (15)

It is possible that our patient possesses a genetic predisposition to immune dysfunction. All three diseases may represent a continuum that reflects a progressive decline in immune function. Alternatively, they may represent three random consequences of an immune system that has become grossly disordered. Our single case does not help to distinguish the relationship between these diseases. The occurrence of ITP, CS, and IBM together in our patient, however, supports the possibility that they may share a common immune pathogenesis.

Table 1

Summary of laboratory data at initial presentation and follow-up (a)

                                Initial            Normal
Test                            data               range

Antigliadin antibody            Negative
Antinuclear antibody            Positive 1:        < 1:40
                                160
Anti-Smith antibody             Negative
Alanine aminotransferase (b)    134 U/L            9-29
Albumin                         3.8 g/dl
Aldolase                        22.6 U/L           0-7.3
Aspartate aminotransferase (b)  67 U/L             12-31
Calcium                         10.3 mg/dl
Creatine kinase (b)             1,582 U/L          38-176
Cratinine                       0.4 mg/dl          0.6-0.9
Endomysial antibodies,          Positive           Negative
 immunoglobulin A (b)
Erythrocyte sedimentation rate  33 mm/hr           0-29
Extranuclear antigens           2.0 U
Glucose                         65 mg/dl           70-100
Hemoglobin                      12.7 g/dl
Iron                            85 [micro]g/dl
Iron saturation (%)             26
Lactate dehydrogenase (b)       662 U/L            98-221
Platelet count (b)              80,000/[mm.sup.3]  150,000-450,000
Sodium                          139 mEq/L
Thyroid-stimulating hormone     2.5 mIU/L
Total iron-binding capacity     331 [micro]g/dl
Total protein (b)               8.4 g/dl           6.3-7.9
[gamma]-Globulin (b)            2.6 g/dl           0.7-1.6
Vitamin [B.sub.12]              >2,000 ng/L        190-900

                                Follow-up
Test                            data

Antigliadin antibody
Antinuclear antibody

Anti-Smith antibody
Alanine aminotransferase (b)    62 U/L
Albumin
Aldolase                        8.9 U/L
Aspartate aminotransferase (b)  32 U/L
Calcium
Creatine kinase (b)             238 U/L
Cratinine
Endomysial antibodies,
 immunoglobulin A (b)
Erythrocyte sedimentation rate
Extranuclear antigens
Glucose                         75
Hemoglobin
Iron
Iron saturation (%)
Lactate dehydrogenase (b)       332 U/L
Platelet count (b)              89,000
Sodium
Thyroid-stimulating hormone
Total iron-binding capacity
Total protein (b)
[gamma]-Globulin (b)
Vitamin [B.sub.12]

(a)Initial data were collected at presentation, and follow-up data were
collected on hospital days 5 through 8.

(b)Pertinent out-of-limit values.

Accepted May 28, 2002.

References

(1.) Mikol J, Engel AG. Inclusion body myositis, in Engel A, Franzini- Armstrong C (eds): Myology: Basic and Clinical. New York, McGraw-Hill Health Professions Division, 1994, ed 2, pp 1384-1396.

(2.) Murray JA. The widening spectrum of celiac disease. Am J Clin Nutr 1999;69:354-365.

(3.) George JN, Rizvi MA. Thrombocytopenia, in Beutler E, Williams WJ (eds): Williams Hematology. New York, McGraw-Hill, 2001, cd 6, pp 1495-1527.

(4.) Schuppan D. Current concepts of celiac disease pathogenesis. Gastroenterology 2000;119:234-242.

(5.) Jandl JH. Disorders of platelets, in Jandl JH (ed): Blood: Textbook of Hematology. Boston, Little, Brown, 1996, ed 2, pp 1301-1344.

(6.) Eliakim R, Heyman S, Kornberg A. Celiac disease and keratoconjunetivitis: Occurrence with thrombocytopenic purpura. Arch Intern Med 1982;142:1037.

(7.) Mulder CJ, Pena AS, Jansen J, Oosterhuis JA. Celiac disease and geographic (serpiginous) choroidopathy with occurrence of thrombocytopenic purpura. Arch Intern Med 1983;143:842 (letter).

(8.) Mulder CJ, Gratama JW, Trimbos-Kemper GC, Willemze R, Pena AS. Thrombocytopenic purpura, coeliac disease and IgA deficiency. Neth J Med 1986;29:165-166.

(9.) Stene-Larsen G, Mosvold J, Ly B. Selective vitamin [B.sub.12] malabsorption in adult coeliac disease: Report on three cases with associated autoimmune diseases. Scand J Gastroenterol 1988;23:1105-1108.

(10.) Sheehan NJ, Stanton-King K. Polyautoimmunity in a young woman. Br J Rheumatol 1993;32:254-256.

(11.) Kahn O, Fiel MI, Janowitz HD. Celiac sprue, idiopathic thrombocytopenic purpura, and hepatic granulomatous disease: An autoimmune linkage? J Clin Gastroenterol 1996;23:214-216.

(12.) Riggs JE, Schochet SS Jr. Gutmann L, McComas CF, Rogers JS II. Inclusion body myositis and chronic immune thrombocytopenia. Arch Neural 1984;41:93-95.

(13.) Gause A, Inderrieden DC, Laas R, Arlt AC, Gross WL. Common variable immunodeficiency (CVID) and inclusion body myositis (IBM). Immunobiology 2000;202:199-203.

(14.) Hadjivassiliou M, Chattopadhyay AK, Davies-Jones GA, Gibson A, Grunewald RA, Lobo AJ. Neuromuscular disorder as a presenting feature of coeliac disease. J Neural Neurosurg Psychiatry 1997;63:770-775.

(15.) Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med 1991;325:1487-1498.

RELATED ARTICLE: Key Points

* In this report, inclusion body myositis, celiac sprue, and idiopathic thrombocytopenic purpura all occurred in the same patient.

* The pathogenesis of inclusion body myositis may involve immune dysfunction.

* This case suggests that inclusion body myositis, celiac sprue, and idiopathic thrombocytopenic purpura may share an interrelated immune mechanism.

Case Report

A 51-year-old woman presented with a 14-year history of diarrhea and 6 years of progressive weakness. She had been given provisional diagnoses of irritable bowel syndrome and limb girdle muscular dystrophy, but confirmatory testing had not been performed. The diarrhea was characterized by 2 to 10 bowel movements daily, accompanied by urgency but no pain. Symptoms were unrelenting, and she had a 60-lb weight loss in the 3 years before our evaluation. Six years before presentation, she began to have proximal muscle weakness, with difficulty climbing stairs and blow-drying her hair. The weakness progressed, and she eventually required assistance to walk.

Her medical history was significant only for ITP, diagnosed incidentally at age 38 and not requiring treatment. Her medications included chlordiazepoxide, alprazolam, loperamide hydrochloride, multivitamin, creatine, St. John's wort parenteral vitamin [B.sub.12], and calcium. Social and family histories were noncontributory. On review of systems, the patient reported only several months of amenorrhea. Physical examination revealed an emaciated white woman. Height was 167 cm and weight was 34.7 kg. The pulse rate was 84 beats/mm and blood pressure was 92/70 mm Hg. Chest and cardiopulmonary examinations were unremarkable. The abdomen was nondistended and nontender, with no organomegaly. There was trace bipedal edema. Her voice was weak. She was able to stand but was unable to walk. There was severe, diffuse, symmetric muscle atrophy (Fig. 1). Strength was markedly diminished in the proximal muscles, and was also diminished in the distal muscles, though less so. Muscle tone was normal. There were no abnormal mov ements or fasciculations. Deep tendon reflexes were mildly and diffusely diminished. Results of sensory examination and cerebellar testing were normal.

Initial laboratory data are shown in Table 1. Significant findings included a polyclonal hypergammaglobulinemia and elevations of creatine kinase, aldolase, lactate dehydrogenase, and transaminases. Electromyographic findings were nonspecific and suggestive of either a lower motor neuron process or a primary myopathy. Tissue was obtained for biopsy from the left deltoid muscle. Upper endoscopy and biopsy of small bowel mucosa revealed partial villous atrophy and other findings consistent with a diagnosis of celiac sprue (Fig. 2). Testing for antigliadin antibody was negative; immunoglobulin A antiendomysial antibody testing was positive.

Nutritional support with a gluten-free diet was initiated after hospitalization and gastrostomy tube placement. While awaiting muscle biopsy results, empiric high-dose corticosteroid therapy was started for a presumptive diagnosis of polymyositis. Subsequent biopsy results showed the presence of rimmed vacuoles consistent with IBM (Fig. 3). After 9 days of hospitalization, muscle enzymes had decreased (Table 1) and the diarrhea had markedly improved. Muscle strength and platelet count (Table) remained unchanged. Three months later, the patient reported a 12-lb weight gain and a subjective increase in muscle strength.

From the Divisions or General Internal Medicine and Rheumatology, Mayo Clinic Jacksonville, Jacksonville, FL.

Reprint requests to Betty A. Mincey, MD, Mayo Clinic, 4500 San Pablo Road. Jacksonville, FL 32224. Email: [e-mail]

Copyright [C] 2003 by The Southern Medical Association

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