Topical Review—Connective Tissue Diseases: Orofacial Manifestations Including Pain

This topical review presents an overview of orofacial manifestations associated with the more common connective tissue diseases affecting multiple organs. The orofacial manifestations associated with these autoimmune disorders include oral mucosa alterations, salivary gland pathosis, sensory neuropathies, headaches, and temporomandibular disorders. Since many of these orofacial manifestations may be painful, the practitioner managing pain patients should be familiar with them. An understanding of the orofacial manifestations associated with these systemic diseases will enable the pain practitioner to establish an appropriate diagnosis within the context of the underlying systemic disease. This will allow the practitioner the opportunity to contribute and collaborate as a member of a multidisciplinary health-care team in the management of these systemic autoimmune diseases.

connective tissue disease; headache; orofacial manifestation; temporomandibular disorders; trigeminal neuropathy

1. Ward MM. Prevalence of physician-diagnosed systemic lupus erythematosus in the United States: Results from the third national health and nutrition examination survey. J Womens Health (Larchmt) 2004;13:713–718.

2. Hahn B. Systemic lupus erythematosus. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL (eds). Harrison’s Principles of Internal Medicine. New York: McGraw Hill, 2005:1960–1967.

3. Little JW, Falace DA, Miller CS, Rhodus NL. Arthritic Diseases. In: Dental Management of the Medically Compromised Patient. St. Louis: CV Mosby, 2002: 478–500.

4. Klippel JH. Systemic lupus erythematosus. Treatment-related complications superimposed on chronic disease. JAMA 1990;263:1812–1815.

5. Petri M, Genovese M. Incidence of and risk factors for hospitalizations in systemic lupus erythematosus: A prospective study of the Hopkins Lupus Cohort. J Rheumatol 1992;19:1559–1565.

6. Taasiulas I, Lockshin MD. Systemic Lupus Erythematosus. In: Yee AMF, Paget SA (eds). Expert Guide to Rheumatology. Philadelphia: American College of Physicians, 2005:71–94.

7. Rhodus NL, Johnson DK. The prevalence of oral manifestations of systemic lupus erythematosus. Quintessence Int 1990;21:461–465.

8. Schiodt M, Halberg P, Hentzer B. A clinical study of 32 patients with oral discoid lupus erythematosus. Int J Oral Surg 1978;7:85–94.

9. Herschfus L. Lupus erythematosus. J Oral Med 1972; 27:12–18.

10. Sugarman MM. Lupus erythematosus. Oral Surg Oral Med Oral Pathol 1953;6:836–842.

11. Martin DW. Lupus erythematosus—its oral manifestations. Oral Surg Oral Med Oral Pathol 1970;29:846–848.

12. Vitali C, Doria A, Tincani A, et al. International survey on the management of patients with SLE. I. General data on the participating centers and the results of a questionnaire regarding mucocutaneous involvement. Clin Exp Rheumatol 1996;14:S17–S22.

13. Urman JD, Lowenstein MB, Abeles M, Weinstein A. Oral mucosal ulceration in systemic lupus erythematosus. Arthritis Rheum 1978;21:58–61.

14. Jonsson R, Heyden G, Westberg NG, Nyberg G. Oral mucosal lesions in systemic lupus erythematosus—A clinical, histopathological and immunopathological study. J Rheumatol 1984;11:38–42.

15. Bacon PA. Vasculitic syndromes associated with other rheumatic conditions and unclassified systemic vasculitis. Curr Opin Rheumatol 1991;3:56–61.

16. Jorizzo JL, Salisbury PL, Rogers RS, 3rd, Goldsmith SM, Shar GG, Callen JP, et al. Oral lesions in systemic lupus erythematosus. Do ulcerative lesions represent a necrotizing vasculitis? J Am Acad Dermatol 1992;27:389–394.

17. Gerbracht D, Shapiro L. Temporomandibular joint erosions in systemic lupus erythematosus. Arthritis Rheum 1982;25:597.

18. Liebling MR, Gold RH. Erosions of the temporomandibular joint in systemic lupus erythematosus. Arthritis Rheum 1981;24:948–950.

19. Donaldson KW. Rheumatoid diseases and the temporomandibular joint: A review. Cranio 1995;13:264–269.

20. Jonsson R, Lindvall AM, Nyberg G. Temporomandibular joint involvement in systemic lupus erythematosus. Arthritis Rheum 1983;26:1506–1510.

21. Ashworth B, Tait GB. Trigeminal neuropathy in connective tissue disease. Neurology 1971;21:609–614.

22. Lundberg PO, Werner I. Trigeminal sensory neuropathy in systemic lupus erythematosus. Acta Neurol Scand 1972;48:330–340.

23. Hagen NA, Stevens JC, Michet CJ Jr. Trigeminal sensory neuropathy associated with connective tissue diseases. Neurology 1990;40:891–896.

24. Shotts RH, Porter SR, Kumar N, Scully C. Longstanding trigeminal sensory neuropathy of nontraumatic cause. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:572–576.

25. Robinson CM, Addy L, Wylie M, Luker J, Eveson JW, Prime SS. A study of the clinical characteristics of benign trigeminal sensory neuropathy. J Oral Maxillofac Surg 2003;61:325–332.

26. Mitsikostas DD, Sfikakis PP, Goadsby PJ. A meta-analysis for headache in systemic lupus erythematosus: The evidence and the myth. Brain 2004;127:1200–1209.

27. Cuadrado MJ, Sanna G. Headache and systemic lupus erythematosus. Lupus 2003;12:943–946.

28. Carron JD, Karakla DW, Watkins DV. Focal parotid necrosis in systemic lupus erythematosus: Case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:455–460.

29. Ogura N, Fujisaku A, Jodo S, et al. Lupus erythematosus profundus around the salivary glands: A case resembling submandibular salivary gland disease. Lupus 1997;6: 477–479.

30. Dunn P, Kuo TT, Shih LY, et al. Primary salivary gland lymphoma: A clinicopathologic study of 23 cases in Taiwan. Acta Haematol 2004;112:203–208.

31. Bayar N, Kara SA, Keles I, Koc MC, Altinok D, Orkun S. Temporomandibular joint involvement in rheumatoid arthritis: A radiological and clinical study. Cranio 2002;20:105–110.

32. Helenius LM, Hallikainen D, Helenius I, et al. Clinical and radiographic findings of the temporomandibular joint in patients with various rheumatic diseases. A case-control study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:455–463.

33. Koh ET, Yap AU, Koh CK, Chee TS, Chan SP, Boudville IC. Temporomandibular disorders in rheumatoid arthritis. J Rheumatol 1999;26:1918–1922.

34. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001; 344:907–916.

35. Ebringer A Rashid T, Wilson C. Rheumatoid arthritis: Proposal for the use of anti-microbial therapy in early cases. Scand J Rheumatol 2003;32:2–11.

36. Oliver JE, Worthington J, Silman AJ. Genetic epidemiology of rheumatoid arthritis. Curr Opin Rheumatol 2006; 18:141–146.

37. Dodeller F, Schulze-Koops H. The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells. Arthritis Res Ther 2006;8:205.

38. Dombrecht EJ, Aerts NE, Schuerwegh AJ, et al. Influence of anti-tumor necrosis factor therapy (Adalimumab) on regulatory T cells and dendritic cells in rheumatoid arthritis. Clin Exp Rheumatol 2006;24:31–37.

39. Symmons DP, Barrett EM, Bankhead CR, Scott DG, Silman AJ. The incidence of rheumatoid arthritis in the United Kingdom:Results from the Norfolk Arthritis Register. Br J Rheumatol 1994;33:735–739.

40. Yelin E. Arthritis. The cumulative impact of a common chronic condition. Arthritis Rheum 1992;35:489–497.

41. Laskin D. The clinical diagnosis of temporomandibular disorders in the orthodontic patient. Semin Orthod 1995; 1:197–206.

42. Moen K, Bertelsen LT, Hellem S, Jonsson R, Brun JG. Salivary gland and temporomandibular joint involvement in rheumatoid arthritis: Relation to disease activity. Oral Dis 2005;11:27–34.

43. Paget SA. Rheumatoid arthritis. In: Yee AMF, Paget SA (eds). Expert Guide to Rheumatology. Philadelphia: American College of Physicians, 2005:29–48.

44. Gleissner C, Kaesser U, Dehne F, Bolten WW, Willershausen B. Temporomandibular joint function in patients with longstanding rheumatoid arthritis. I. Role of periodontal status and prosthetic care-A clinical study. Eur J Med Res 2003;8:98–108.

45. Tabeling HJ, Dolwick MF. Rheumatoid arthritis: Diagnosis and treatment. Fla Dent J 1985;56:16–18.

46. Larheim TA, Smith HJ, Aspestrand F. Rheumatic disease of the temporomandibular joint: MR imaging and tomographic manifestations. Radiology 1990;175:527–531.

47. Wenneberg B, Kononen M, Kallenberg A. Radiographic changes in the temporomandibular joint of patients with rheumatoid arthritis, psoriatic, arthritis, and ankylosing spondylitis. J Craniomandib Disord 1990;4:35–39.

48. Voog U, Alstergren P, Eliasson S, Leibur E, Kallikorm R, Kopp S. Inflammatory mediators and radiographic changes in temporomandibular joints of patients with rheumatoid arthritis. Acta Odontol Scand 2003;61:57–64.

49. Celiker R, Gokce-Kutsal Y, Eryilmaz M. Temporomandibular joint involvement in rheumatoid arthritis. Relationship with disease activity. Scand J Rheumatol 1995;24:22–25.

50. Kononen M, Wenneberg B, Kallenberg A. Craniomandibular disorders in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A clinical study. Acta Odontol Scand 1992;50:281–287.

51. Atsu SS, Ayhan-Ardic F. Temporomandibular disorders seen in rheumatology practices: A review. Rheumatol Int 2006;26:781–787.

52. Ardic F, Gokharman D, Atsu S, Guner S, Yilmaz M, Yorgancioglu R. The comprehensive evaluation of temporomandibular disorders seen in rheumatoid arthritis. Aust Dent J 2006;51:23–28.

53. Kobayashi R, Utsunomiya T, Yamamoto H, Nagura H. Ankylosis of the temporomandibular joint caused by rheumatoid arthritis: A pathological study and review. J Oral Sci 2001;43:97–101.

54. Manfredini D, Tognini F, Melchiorre D, Bazzichi L, Bosco

M. Ultrasonography of the temporomandibular joint: Comparison of findings in patients with rheumatic diseases and temporomandibular disorders. A preliminary report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:481–485.

55. Voog U, Alstergren P, Eliasson S, Leibur E, Kallikorm R, Kopp S. Progression of radiographic changes in the temporomandibular joints of patients with rheumatoid arthritis in relation to inflammatory markers and mediators in the blood. Acta Odontol Scand 2004;62:7–13.

56. Marini I, Vecchiet F, Spiazzi L, Capurso U. Stomatognathic function in juvenile rheumatoid arthritis and in developmental open-bite subjects. ASDC J Dent Child 1999;66:30–35, 12.

57. Kasser UR, Gleissner C, Dehne F, Michel A, Willershausen-Zonnchen B, Bolten WW. Risk for periodontal disease in patients with longstanding rheumatoid arthritis. Arthritis Rheum 1997;40:2248–2251.

58. Tolo K, Jorkjend L. Serum antibodies and loss of periodontal bone in patients with rheumatoid arthritis. J Clin Periodontol 1990;17:288–291.

59. Helenius LM, Meurman JH, Helenius I, et al. Oral and salivary parameters in patients with rheumatic diseases. Acta OdontolScand 2005;63:284–293.

60. Treister N, Glick M. Rheumatoid arthritis: A review and suggested dental care considerations. J Am Dent Assoc 1999;130:689–698.

61. Vilches A, Burke MJ. Trigeminal sensory neuropathy and rheumatoid arthritis: Case study of a rare association. Rheumatology (Oxford) 2001;40:832–833.

62. Forster C, Brandt T, Hund E, et al. Trigeminal sensory neuropathy in connective tissue disease: Evidence for the site of the lesion. Neurology 1996;46:270–271.

63. Tzioufas AG Kassan SS, Moutsopoulos HM. Sjögren’s syndrome. In: Yee AMF, Paget SA (eds). Expert Guide to Rheumatology. Philadelphia: American College of Physicians, 2005:109–122.

64. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren’s syndrome. Arch Intern Med 2004;164:1275–1284.

65. Moutsopoulos H. Sjögren’s Syndrome. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL (eds). Harrison’s Principles of Internal Medicine. New York: McGraw Hill, 2005:1990–1993.

66. Kassan SS, Thomas TL, Moutsopoulos HM, et al. Increased risk of lymphoma in sicca syndrome. Ann Intern Med 1978;89:888–892.

67. Theander E, Henriksson G, Ljungberg O, Mandl T, Manthorpe R, Jacobsson LT. Lymphoma and other malignancies in primary Sjögren’s syndrome: A cohort study on cancer incidence and lymphoma predictors. Ann Rheum Dis 2006;65:796–803.

68. Horiuchi M, Yamano S, Inoue H, et al. Possible involvement of IL-12 expression by Epstein-Barr virus in Sjögren syndrome. J Clin Pathol 1999;52:833–837.

69. Newkirk MM, Shiroky JB, Johnson N, et al. Rheumatic disease patients, prone to Sjögren’s syndrome and/or lymphoma, mount an antibody response to BHRF1, the Epstein-Barr viral homologue of BCL-2. Br J Rheumatol 1996;35:1075–1081.

70. Soto-Rojas AE, Kraus A. The oral side of Sjögren syndrome. Diagnosis and treatment. A review. Arch Med Res 2002;33:95–106.

71. Al-Hashimi I, Khuder S, Haghighat N, Zipp M. Frequency and predictive value of the clinical manifestations in Sjögren’s syndrome. J Oral Pathol Med 2001;30:1–6.

72. Soto-Rojas AE, Villa AR, Sifuentes-Osornio J, Alarcon-Segovia D, Kraus A. Oral manifestations in patients with Sjögren’s syndrome. J Rheumatol 1998;25:906–910.

73. Rhodus NL, Bloomquist C, Liljemark W, Bereuter J. Prevalence, density, and manifestations of oral Candida albicans in patients with Sjögren’s syndrome. J Otolaryngol 1997;26:300–305.

74. Ship JA. Diagnosing, managing, and preventing salivary gland disorders. Oral Dis 2002;8:77–89.

75. Olney RK. Neuropathies associated with connective tissue disease. Semin Neurol 1998;18:63–72.

76. Denislic M, Meh D. Early asymmetric neuropathy in primary Sjögren’s syndrome. J Neurol 1997;244:383–387.

77. Mellgren SI, Conn DL, Stevens JC, Dyck PJ. Peripheral neuropathy in primary Sjögren’s syndrome. Neurology 1989;39:390–394.

78. Grant IA, Hunder GG, Homburger HA, Dyck PJ. Peripheral neuropathy associated with sicca complex. Neurology 1997;48:855–862.

79. Urban PP, Keilmann A, Teichmann EM, Hopf HC. Sensory neuropathy of the trigeminal, glossopharyngeal, and vagal nervesin Sjögren’s syndrome. J Neurol Sci 2001;186:59–63.

80. Mori K, Iijima M, Koike H, et al. The wide spectrum of clinical manifestations in Sjögren’s syndrome-associated neuropathy. Brain 2005;128:2518–2534.

81. Font J, Ramos-Casals M, de la Red G, et al. Pure sensory neuropathy in primary Sjögren’s syndrome. Long-term prospective follow-up and review of the literature. J Rheumatol 2003;30:1552–1557.

82. Urban PP, Forst T, Lenfers M, Koehler J, Connemann BJ, Beyer J. Incidence of subclinical trigeminal and facial nerve involvement in diabetes mellitus. Electromyogr Clin Neurophysiol 1999;39:267–272.

83. Pal B, Gibson C, Passmore J, Griffiths ID, Dick WC. A study of headaches and migraine in Sjögren’s syndrome and other rheumatic disorders. Ann Rheum Dis 1989; 48:312–316.

84. Hietaharju A, Jantti V, Korpela M, Frey H. Nervous system involvement in systemic lupus erythematosus, Sjögren syndromeand scleroderma. Acta Neurol Scand 1993;88: 299–308.

85. Escudero D, Latorre P, Codina M, Coll-Canti J, Coll J. Central nervous system disease in Sjögren’s syndrome. Ann Med Interne (Paris) 1995;146:239–242.

86. Scully C. Oral parameters in the diagnosis of Sjögren’s syndrome. Clin Exp Rheumatol 1989;7:113–117.

87. Mandel L, Surattanont F. Bilateral parotid swelling: A review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:221–237.

88. Netter FH, Dalley AF. Atlas of Human Anatomy. East Hanover, NJ: Novartis, 1997.

89. Okeson JP. Bell’s Orofacial Pains: The Clinical Management of Orofacial Pain. Chicago: Quintessence, 2005.

90. Freeman SR, Sheehan PZ, Thorpe MA, Rutka JA. Ear, nose, and throat manifestations of Sjögren’s syndrome: Retrospective review of a multidisciplinary clinic. J Otolaryngol 2005;34:20–24.

91. Harris NL. Lymphoid proliferations of the salivary glands. Am J Clin Pathol 1999;111:S94–S103.

92. Steinberg AD, Talal N. The coexistence of Sjögren’s syndrome and systemic lupus erythematosus. Ann Intern Med 1971;74:55–61.

93. Alarcon-Segovia D, Ibanez G, Velazquez-Forero F, Hernandez-Ortiz J, Gonzalez-Jimenez Y. Sjögren’s syndrome in systemic lupus erythematosus. Clinical and subclinical manifestations. Ann Intern Med 1974;81: 577–583.

94. Alarcon-Segovia D. Symptomatic Sjögren’s syndrome in mixed connective tissue disease. J Rheumatol 1976;3: 191–195.

95. Andonopoulos AP, Skopouli FN, Dimou GS, Drosos AA, Moutsopoulos HM. Sjögren’s syndrome in systemic lupus erythematosus. J Rheumatol 1990;17:201–204.

96. Gilliland B. Systemic sclerosis (scleroderma) and related disorders. In: Kasper DL Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL (eds). Harrison’s Principles of Internal Medicine. New York: McGraw Hill, 2005: 1979–1989.

97. Schwartzman S, Efthimiou P. Systemic sclerosis and related conditions. In: Yee AMF, Paget SA (eds). Expert Guide to Rheumatology. Philadelphia: American College of Physicians, 2005:135–147.

98. Simms RW, Korn JH. Cytokine directed therapy in scleroderma: Rationale, current status, and the future. Curr Opin Rheumatol 2002;14:717–722.

99. Spackman GK. Scleroderma: What the general dentist should know. Gen Dent 1999;47:576–579.

100. Scardina GA, Messina P. Systemic sclerosis: Description and diagnostic role of the oral phenomena. Gen Dent 2004;52:42–47.

101. Chaffee NR. CREST syndrome: Clinical manifestations and dental management. J Prosthodont 1998;7:155–160.

102. Nagy G, Kovacs J, Zeher M, Czirjak L. Analysis of the oral manifestations of systemic sclerosis. Oral Surg Oral Med Oral Pathol 1994;77:141–146.

103. Wood RE, Lee P. Analysis of the oral manifestations of systemic sclerosis (scleroderma). Oral Surg Oral Med Oral Pathol 1988;65:172–178.

104. Marmary Y, Glaiss R, Pisanty S. Scleroderma: Oral manifestations. Oral Surg Oral Med Oral Pathol 1981;52: 32–37.

105. Ramon Y, Samra H, Oberman M. Mandibular condylosis and apertognathia as presenting symptoms in progressive systemic sclerosis (scleroderma). Pattern of mandibular bony lesions and atrophy of masticatory muscles in PSS, presumably caused by affected muscular arteries. Oral Surg Oral Med Oral Pathol 1987;63:269–274.

106. Teasdall RD, Frayha RA, Shulman LE. Cranial nerve involvement in systemic sclerosis (scleroderma): A report of 10 cases. Medicine (Baltimore) 1980;59:149–159.

107. Lecky BR, Hughes RA, Murray NM. Trigeminal sensory neuropathy. A study of 22 cases. Brain 1987;110: 1463–1485.

108. Nadeau SE. Neurologic manifestations of connective tissue disease. Neurol Clin 2002;20:151–178, vi.

109. Fischoff DK, Sirois D. Painful trigeminal neuropathy caused by severe mandibular resorption and nerve compression in a patient with systemic sclerosis: Case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:456–459.

110. Sari-Kouzel H, Herrick AL, Freemont AJ, Marcuson RW, Jayson MI. Giant cell arteritis in a patient with limited cutaneous systemic sclerosis. Rheumatology (Oxford) 1999;38:479–480.

111. Hupp SL. Giant cell arteritis associated with progressive systemic sclerosis. J Clin Neuroophthalmol 1989;9: 126–130.

112. Perez-Jinenez F, Lopez-Rubio F, Canadillas F, Jimenez-Alonso J, Jimenez-Pereperez J. Giant cell arteritis associated with progressive systemic sclerosis. Arthritis Rheum 1982;25:717–718.

113. Imanguli MM, Pavletic SZ, Guadagnini JP, Brahim JS, Atkinson JC. Chronic graft versus host disease of oral mucosa: Review of available therapies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:175–183.

114. Armitage JO. Bone marrow transplantation. N Engl J Med 1994;330:827–838.

115. Gilliam AC. Update on graft versus host disease. J Invest Dermatol 2004;123:251–257.

116. Ratanatharathorn V, Ayash L, Lazarus HM, Fu J, Uberti JP. Chronic graft-versus-host disease: Clinical manifestation and therapy. Bone Marrow Transplant 2001;28: 121–129.

117. Woo SB, Lee SJ, Schubert MM. Graft-vs.-host disease. Crit Rev Oral Biol Med 1997;8:201–216.

118. Delaleu N, Jonsson R, Koller MM. Sjögren’s syndrome. Eur J Oral Sci 2005;113:101–113.

119. Klein Gunnewiek JM, van de Putte LB, van Venrooij WJ. The U1 snRNP complex: An autoantigen in connective tissue diseases. An update. Clin Exp Rheumatol 1997;15: 549–560.

120. Aringer M, Steiner G, Smolen JS. Does mixed connective tissue disease exist? Yes. Rheum Dis Clin North Am 2005; 31:411–420.

121. Maddison PJ. Overlap syndromes and mixed connective tissue disease. Curr Opin Rheumatol 1991;3:995–1000.

122. Mukerji B, Hardin JG. Undifferentiated, overlapping, and mixed connective tissue diseases. Am J Med Sci 1993;305: 114–119.

123. Swanton J, Isenberg D. Mixed connective tissue disease: Still crazy after all these years. Rheum Dis Clin North Am 2005;31:421–436.

124. Helenius LM, Hietanen JH, Helenius I, et al. Focal sialadenitis in patients with ankylosing spondylitis and spondyloarthropathy: A comparison with patients with rheumatoid arthritis or mixed connective tissue disease. Ann Rheum Dis 2001;60:744–749.

125. Konttinen YT, Tuominen TS, Piirainen HI, et al. Signs and symptoms in the masticatory system in ten patients with mixed connective tissue disease. Scand J Rheumatol 1990; 19:363–373.

126. Varga E, Field EA, Tyldesley WR. Orofacial manifestations of mixed connective tissue disease. Br Dent J 1990; 168:330–331.

127. Johansson EA, Niemi KM, Lassus A, Gripenberg M. Mixed connective tissue disease: A follow-up study of 12 patients with special reference to cold sensitivity and skin manifestations. Acta Derm Venereol 1981;61:225–231.

128. Nedumaran, Rajendran CP, Porkodi R, Parthiban R. Mixed connective tissue disease—Clinical and immunological profile. J Assoc Physicians India 2001;49:412–414.

129. Bennett RM, Bong DM, Spargo BH. Neuropsychiatric problems in mixed connective tissue disease. Am J Med 1978;65:955–962.

130. Alfaro-Giner A, Penarrocha-Diago M, Bagan-Sebastian JV. Orofacial manifestations of mixed connective tissue disease with an uncommon serologic evolution. Oral Surg Oral Med Oral Pathol 1992;73:441–444.

131. Bronshvag MM, Pyrstowsky SD, Traviesa DC. Vascular headaches in mixed connective tissue disease. Headache 1978;18:154–160.

132. Briani C, Doria A, Sarzi-Puttini P, Dalakas MC. Update on idiopathic inflammatory myopathies. Autoimmunity 2006;39:161–170.

133. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975;292:344–347.

134. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975;292:403–407.

135. Adams-Gandhi LB, Boyd AS, King LE Jr. Diagnosis and management of dermatomyositis. Compr Ther 1996; 22:156–164.

136. Werth VP, Callen JP, Ang G, Sullivan KE. Associations of tumor necrosis factor alpha and HLA polymorphisms with adult dermatomyositis: Implications for a unique pathogenesis. J Invest Dermatol 2002;119:617–620.

137. Sarkar K, Weinberg CR, Oddis CV, et al. Seasonal influence on the onset of idiopathic inflammatory myopathies in serologically defined groups. Arthritis Rheum 2005; 52:2433–2438.

138. Pachman LM, Lipton R, Ramsey-Goldman R, et al. History of infection before the onset of juvenile dermatomyositis: Results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry. Arthritis Rheum 2005;53:166–172.

139. Dalakas MC. Molecular immunology and genetics of inflammatory muscle diseases. Arch Neurol 1998;55: 1509–1512.

140. Kuru S, Inukai A, Liang Y, Doyu M, Takano A, Sobue G. Tumor necrosis factor-alpha expression in muscles of polymyositis and dermatomyositis. Acta Neuropathol (Berl) 2000;99:585–588.

141. Wanchu A, Khullar M, Sud A, Bambery P. Nitric oxide production is increased in patients with inflammatory myositis. Nitric Oxide 1999;3:454–458.

142. Shimizu T, Tomita Y, Son K, Nishinarita S, Sawada S, Horie T. Elevation of serum soluble tumour necrosis factor receptors in patients with polymyositis and dermatomyositis. Clin Rheumatol 2000;19:352–359.

143. Sugiura T, Kawaguchi Y, Harigai M, et al. Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: Role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production. J Immunol 2000;164:6593–6600.

144. Nyberg P, Wikman AL, Nennesmo I, Lundberg I. Increased expression of interleukin 1alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis. J Rheumatol 2000; 27:940–948.

145. Lundberg IE, Nyberg P. New developments in the role of cytokines and chemokines in inflammatory myopathies. Curr Opin Rheumatol 1998;10:521–529.

146. Callen JP. Dermatomyositis. Lancet 2000;355:53–57.

147. Callen JP, Wortmann RL. Dermatomyositis. Clin Dermatol 2006;24:363–373.

148. Bohan A, Peter JB, Bowman RL, Pearson CM. Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore) 1977;56:255–286.

149. Spiera R, Kagen L. Extramuscular manifestations in idiopathic inflammatory myopathies. Curr Opin Rheumatol 1998;10:556–561.

150. Marie I, Hatron PY, Hachulla E, Wallaert B, Michon-Pasturel U, Devulder B. Pulmonary involvement in polymyositis and in dermatomyositis. J Rheumatol 1998; 25:1336–1343.

151. Gonzalez-Lopez L, Gamez-Nava JI, Sanchez L, et al. Cardiac manifestations in dermato-polymyositis. Clin Exp Rheumatol 1996;14:373–379.

152. Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: A population-based study. Lancet 2001;357:96–100.

153. Whitmore SE, Rosenshein NB, Provost TT. Ovarian cancer in patients with dermatomyositis. Medicine (Baltimore) 1994;73:153–160.

154. Peng JC, Sheen TS, Hsu MM. Nasopharyngeal carcinoma with dermatomyositis. Analysis of 12 cases. Arch Otolaryngol Head Neck Surg 1995;121:1298–1301.

155. Dourmishev AL, Dourmishev LA. Dermatomyositis and drugs. Adv Exp Med Biol 1999;455:187–191.

156. Daoud MS, Gibson LE, Pittelkow MR. Hydroxyurea dermopathy: A unique lichenoid eruption complicating longterm therapy with hydroxyurea. J Am Acad Dermatol 1997;36:178–182.

157. Grob JJ, Collet AM, Bonerandi JJ. Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents. Dermatologica 1989;178:58–59.

158. Flendrie M, Vissers WH, Creemers MC, de Jong EM, van de Kerkhof PC, van Riel PL. Dermatological conditions during TNF-alpha-blocking therapy in patients with rheumatoid arthritis: A prospective study. Arthritis Res Ther 2005;7:R666–R676.

159. Sanger RG, Kirby JW. The oral and facial manifestations of dermatomyositis with calcinosis. Report of a case. Oral Surg Oral Med Oral Pathol 1973;35:476–488.

160. Chauvet E, Sailler L, Carreiro M, et al. Symptomatic macroglossia and tongue myositis in polymyositis: Treatment with corticosteroids and intravenous immunoglobulin. Arthritis Rheum 2002;46:2762–2764.

161. Healy CM, Tobin AM, Kirby B, Flint SR. Oral lesions as an initial manifestation of dermatomyositis with occult malignancy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:184–187.

162. Ghali FE, Stein LD, Fine JD, Burkes EJ, McCauliffe DP. Gingival telangiectases: An underappreciated physical sign of juvenile dermatomyositis. Arch Dermatol 1999;135: 1370–1374.

163. Peretz B. Juvenile dermatomyositis: Literature review and report of a case. Compend Contin Educ Dent 2001;22: 858–862, 864.

164. Marton K, Hermann P, Danko K, Fejerdy P, Madlena M, Nagy G. Evaluation of oral manifestations and masticatory force in patients with polymyositis and dermatomyositis. J Oral Pathol Med 2005;34:164–169.

165. Brennan MT, Patronas NJ, Brahim JS. Bilateral condylar resorption in dermatomyositis: A case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87: 446–451.

166. Citera G, Goni MA, Maldonado Cocco JA, Scheines EJ. Joint involvement in polymyositis/dermatomyositis. Clin Rheumatol 1994;13:70–74.