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 inclusion body myositis A type of idiopathic myositis that is not autoimmune and does not respond to immunosuppressive therapy, a clinical diagnosis of exclusion, confirmed by typical histologic features Clinical Slowly progressive disease of middle-aged ♂, associated with celiac sprue and idiopathic thrombocytopenic purpura Idiopathic Thrombocytopenic Purpura Definition
Idiopathic thrombocytopenic purpura, or ITP, is a bleeding disorder caused by an abnormally low level of platelets in the patient's blood. . We propose that the presence of all three disorders together suggests that they may share an interrelated immune mechanism.
Inclusion body myositis (IBM) is an inflammatory myoplathy characterized by progressive muscle weakness. Unlike the other inflammatory myopathies Myopathies Definition
Myopathies are diseases of skeletal muscle which are not caused by nerve disorders. These diseases cause the skeletal or voluntary muscles to become weak or wasted. , 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 ITP - Intent to Package ) is characterized by a low platelet count, normally functioning bone marrow, and the absence of other disorders that may account for thrombocytopenia Thrombocytopenia Definition
Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets. . Patients with ITP may be asymptomatic or may present with easy bruising, menorrhagia menorrhagia /men·or·rha·gia/ (men?ah-ra´jah) hypermenorrhea.
See hypermenorrhea. , 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.
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 sensitized /sen·si·tized/ (sen´si-tizd) rendered sensitive.
see sensitization (2). 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 autoantigen /au·to·an·ti·gen/ (-an´ti-jen) an antigen that despite being a normal tissue constituent is the target of a humoral or cell-mediated immune response, as in autoimmune disease. . (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.
(1.) Mikol J, Engel AG. Inclusion body myositis, in Engel A, Franzini- Armstrong C (eds): Myology myology /my·ol·o·gy/ (mi-ol´ah-je) the scientific study or description of the muscles and accessory structures (bursae and synovial sheath).
The scientific study of muscles. : 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 serpiginous /ser·pig·i·nous/ (ser-pij´i-nus) creeping; having a wavy or much indented border.
adj. ) 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 Common Variable Immunodeficiency Definition
Common variable immunodeficiency is an immunodeficiency disorder characterized by a low level of antibodies. Patients with this disease are subject to recurring infections. (CVID CVID common variable immunodeficiency.
CVID Common variable immune deficiency, see there ) 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 Polymyositis Definition
Polymyositis is an inflammatory muscle disease causing weakness and pain. Dermatomyositis is identical to polymyositis with the addition of a characteristic skin rash. , dermatomyositis Dermatomyositis Definition
Dermatomyositis (DM) is a rare inflammatory muscle disease that leads to destruction of muscle tissue usually accompanied by pain and weakness. and inclusion-body myositis myositis
Inflammation of muscle tissue, often from bacterial, viral, or parasitic infection but sometimes of unknown origin. Most types destroy muscle and surrounding tissue. Bacteria may directly infect muscle (usually after injury) or produce substances toxic to it. . 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.
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 irritable bowel syndrome (IBS), condition characterized by frequently alternating constipation and diarrhea in the absence of any disease process. It is usually accompanied by abdominal pain, especially in the lower left quadrant, bloating, and flatulence. 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 chlordiazepoxide /chlor·di·az·ep·ox·ide/ (klor?di-az?e-pok´sid) a benzodiazepine used as the base or hydrochloride salt in the treatment of anxiety disorders and short-term or preoperative anxiety, for alcohol withdrawal, and as an , alprazolam alprazolam /al·pra·zo·lam/ (al-pra´zo-lam) a benzodiazepine used as an antianxiety agent.
A benzodiazepine tranquilizer that is used in the management of anxiety disorders. , loperamide hydrochloride, multivitamin mul·ti·vi·ta·min
Containing many vitamins.
A preparation containing many vitamins.
multivitamin , creatine, St. John's wort St. John’s wort
indicates animosity. [Flower Symbolism: Flora Symbolica, 177]
See : Hatred
St. John’s wort
defense against fairies, evil spirits, the Devil. [Br. 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 amenorrhea (āmĕn'ərē`a, əmĕn'–), cessation of menstruation. Primary amenorrhea is a delay in or a failure to start menstruation; secondary amenorrhea is an unexpected stop to the menstrual cycle. . Physical examination revealed an emaciated e·ma·ci·ate
tr. & intr.v. e·ma·ci·at·ed, e·ma·ci·at·ing, e·ma·ci·ates
To make or become extremely thin, especially as a result of starvation. 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 bipedal adjective Capable of locomotion on 2 feet 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 aldolase /al·do·lase/ (al´do-las)
2. an enzyme that acts as a catalyst in the production of dihydroxyacetone phosphate and glyceraldehyde phosphate from fructose 1,6-bisphosphate. , lactate dehydrogenase, and transaminases. Electromyographic findings were nonspecific and suggestive of either a lower motor neuron lower motor neuron
A motor neuron whose cell body is located in the brainstem or the spinal cord and whose axon innervates skeletal muscle fibers. Also called final motor neuron. process or a primary myopathy myopathy /my·op·a·thy/ (mi-op´ah-the) any disease of muscle.myopath´ic
centronuclear myopathy myotubular m. . Tissue was obtained for biopsy from the left deltoid muscle deltoid muscle
A muscle with origin from the lateral third of the clavicle, the lateral border of acromion process, and the lower border of spine of scapula, with insertion to the side of the shaft of the humerus, with nerve supply from the axillary . Upper endoscopy and biopsy of small bowel mucosa revealed partial villous villous /vil·lous/ (vil´us) villose.
vil·lous or vil·lose
Of, relating to, resembling, or covered with villi.
pertaining to or emanating from villi. 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.
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