Overlap syndromes in autoimmune connective tissue diseases
DOI:
https://doi.org/10.2478/amb-2024-0044Keywords:
connective tissue diseases, overlap syndromes, Sharp’s syndrome, Rhupus syndrome, Rowell’s syndrome, scleromyositis, lupus erythematosus/lichen planus overlap syndrome, Reynolds syndrome, Senear–Usher syndromeAbstract
Autoimmune connective tissue diseases are a group of immune disorders, characterized by different clinical features, which affects not only the skin but also different organs and systems. Such diseases include: rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, dermatomyositis and polymyositis. However, there are patients that fulfil the diagnostic criteria of more than one disorder, thus supporting the concept of the so called “overlap syndromes”. The aim of this review
is to present the history, clinical and immunologic hallmarks of these overlap syndromes. Such conditions are scleromyositis, lupus erythematosus/lichen planus overlap, Sharp’s syndrome, Rhupus syndrome, Rowell’s syndrome, Reynolds syndrome and Senear-Usher syndromes. Patients with these syndromes usually do not meet most of the diagnostic criteria of “classic” connective tissue diseases and this usually causes diagnostic difficulties. Overlap syndromes are commonly treated with corticosteroids, hydroxychloroquine and immunosuppressant drugs as a first-line treatment. The new therapeutic molecules that precisely interact with immune mechanisms will require accurate diagnosis and a better understanding of the pathogenesis of the overlap syndromes.
References
Mosca M, Tani C, Bombardieri S. Undifferentiated connective tissue diseases (UCTD): a new frontier for rheumatology. Best Pract Res Clin Rheumatol. 2007;21(6):1011-23.
Moinzadeh P, Aberer E, Ahmadi-Simab K, et al. Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2015; 74(4):730-7.
Sharp GC, Irvin WS, Tan EM, et al. Mixed connective tissue disease – an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972; 52(2):148-59.
Rosenthal M. “Mixed connective tissue disease” or “sharp syndrome”. Arthritis Rheum. 1977; 20(3):905-6.
Wolff-Vorbeck G, Hackl W, Fenning S, et al. Characterization of an HLA-DR4-restricted T cell clone recognizing a protein moiety of small nuclear ribonucleoproteins (UsnRNP). Clin Exp Immunol. 1994; 95(3):378-84.
Hamza M, Annabi A, Ayed K, et al. Connectivite mixte (syndrome de Sharp) avec atteinte trijéminée et paralysie faciale. Sem Hop. 1983; 59(36):2555-6.
Remacle P, Bruart J, Henneghien C, Schreiber S. Hypertension pulmonaire fatale dans un syndrome de Sharp (M.C.T.D.) avec fibrose pulmonaire. Rev Med Brux. 1990; 11(1-2):26-30.
Karoui M, Haji F, Ghedira S, et al. Syndrome de Sharp et neuropathie vaguale. Tunis Med. 1990; 68(3):225-9.
Bohn S, Büchner S, Itin P. Erythema nodosum: 112 Fälle. Epidemiologie, Klinik und Histopathologie. Schweiz Med Wochenschr. 1997; 127(27-28):1168-76.
Ndiaye M, Hane AA, Dieng MT, et al. Syndrome de Sharp compliqué d’une tuberculose pulmonaire: àpropos d’un cas. Dakar Med. 1999; 44(2):236-9.
Slimani S, Sahraoui M, Bennadji A, Ladjouze-Rezig A. Syndrome de Sharp réversible après l’ablation d’un schwannome bénin: un syndrome paranéoplasique? Neurochirurgie. 2014; 60(4):194-6.
Nosáková L, Schnierer M, Bánovčin P, et al. Gastrointestinal tract involvement in mixed connective tissue disease (Sharp syndrome). Vnitr Lek. 2020; 66(6):53-57.
Wanzenried A, Garaiman A, Jordan S, et al. The enigma of mixed connective tissue disease-challenges in routine care. Clin Rheumatol. 2022; 41(11):3503-3511.
Panush RS, Edwards NL, Longley S, Webster E. ‘Rhupus’ syndrome. Arch Intern Med. 1988; 148(7):1633-6. 15. Schur PH. Systemic lupus erythematosus. In: Beeson PB, McDermott W, editors. Cecil-loeb Textbook of Medicine. 13th ed. Philadelphia, PA: W.B. Saunders; 1971. p. 821.
Frade-Sosa B, Narváez J, Salman-Monte TC, et al. A comparative study on clinical and serological characteristics between patients with rhupus and those with systemic lupus erythematosus and rheumatoid arthritis. Lupus. 2020; 29(10):1216-1226.
Piga M, Gabba A, Cauli A, et al. Rituximab treatment for ‘rhupus syndrome’: clinical and power-Doppler ultrasonographic monitoring of response. A longitudinal pilot study. Lupus. 2013; 22(6):624-8.
Danion F, Sparsa L, Arnaud L, et al. Long-term efficacy and safety of anti tumor necrosis factor alpha treatment in rhupus: an open-label study of 15 patients. RMD Open. 2017; 3(2):e000555.
Rowell NR, Beck SJ, Anderson JR. Lupus erythematosus and erythema multiforme-like lesions. Arch Dermatol 1963; 88(2):176-180.
Pozharashka J, Dourmishev L, Balabanova M, et al. Rowell’s syndrome triggered by omeprazole: case report and review of
the literature. Acta Dermatovenerol Croat 2019; 27(2):124-6.
Drenovska K, Shahid M, Mateeva V, Vassileva S. Case Report: Rowell Syndrome-Like Flare of Cutaneous Lupus Erythematosus Following COVID-19 Infection. Front Med (Lausanne). 2022; 9:815743.
Costner MI, Sontheimer RD. Lupus erythematosus. In: Freedberg IM, Eisen AZ, Wolff K, et al., eds. Dermatology in General Medicine, 6th edn. New York: McGraw-Hill, 2003: 1677–1693.
Zeitouni NC, Funaro D, Cloutier RA, et al. Redefining Rowell’s syndrome. Br J Dermatol. 2000; 142(2):343-6.
Torchia D, Romanelli P, Kerdel FA. Erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis associated with lupus erythematosus. J Am Acad Dermatol. 2012; 67(3):417-21.
Antiga E, Caproni M, Bonciani D, et al. The last word on the so-called ‘Rowell’s syndrome’? Lupus. 2012; 21(6):577-85.
Roujeau JC, Revuz J. Encore un «dernier mot» sur le syndrome de Rowell. Ann Dermatol Venereol. 2017; 144(8-9):e1-e3. French.
Kim SS, Magro C, Granstein RD, et al. Systemic Lupus Erythematosus Associated with Rowell’s Syndrome: A Clinical Pathology Conference Held by the Division of Rheumatology at Hospital for Special Surgery. HSS J. 2013; 9(3):289-92.
Chandra A, Saha SK, Ray AK, Karmakar P. Rowell’s syndrome: a rare but distinct entity in rheumatology. BMJ Case Rep. 2020; 3(9):e235173.
Chua SH, Giam YC, Sim CS. Systemic lupus erythematosus with erythema multiforme-like lesions and histiocytic necrotizing lymphadenitis - a case report. Ann Acad Med Singap. 1996; 25(4):599-601.
Pandhi D, Singal A, Agarwal P. Rowell’s syndrome and associated antiphospholipid syndrome. Clin Exp Dermatol. 2004; 29(1):22-4.
Shahid S, Khan M, Qadar LT, et al. The First Case of Rowell Syndrome with Lupus Nephritis and Lobar Pneumonia in a Male Child Reported in Pakistan. Cureus. 2019; 11(5):e4604.
Aguirre-Martinez I, Vélez-Tirado N, García-Romero MT, et al. Rowell syndrome complicated with macrophage activation syndrome in a child. Lupus. 2019; 28(14):1716-1721.
Almansouri AY, Alzahrani ZA. A Case of Rhupus with Rowell Syndrome. Open Access Rheumatol. 2020; 12:91-96.
Zhang M, Lu J, Zhang B, et al. Rowell’s Syndrome with Lupus Hepatitis: A Case Report from China. Indian J Dermatol. 2020; 65(6):549-550.
Challa M, Baisya R, Devarasetti PK. Rowell Syndrome with Good Response to Methotrexate. Mediterr J Rheumatol. 2022; 33(1):92-93.
Shope C, Andrews L, Cunningham M, Connett J. A case of Rowell syndrome with excellent improvement following anifrolumab. JAAD Case Rep. 2022; 31:27-30.
Mimori T. Scleroderma-polymyositis overlap syndrome. Clinical and serologic aspects. Int J Dermatol. 1987; 26(7):419-25.
Błaszczyk M, Jabłońska S, Szymańska-Jagiełło W, et al. Childhood scleromyositis: an overlap syndrome associated with PM-Scl antibody. Pediatr Dermatol. 1991; 8(1):1-8.
Mahler M, Raijmakers R. Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmun Rev. 2007;6(7):432-7.
Giannini M, Ellezam B, Leclair V, et al. Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis. Front Immunol. 2023; 13:974078.
Bhansing KJ, van Riel PL, van Engelen BG, et al. Patients with Systemic Sclerosis/polymyositis Overlap Have a Worse Survival Rate Than Patients Without It. J Rheumatol. 2016; 43(10):1838-1843.
Álvarez Troncoso J, Nuño González A, Martínez Robles E, et al. Tofacitinib Is an Effective Treatment for Refractory Scleromyositis Associated with Anti-PM/Scl. Cureus. 2023; 15(1):e34125.
Van der Horst JC, Cirkel PK, Nieboer C. Mixed lichen planuslupus erythematosus disease: a distinct entity? Clinical, histopathological and immunopathological studies in six patients. Clin Exp Dermatol. 1983; 8(6):631-40.
Demirci GT, Altunay IK, Sarıkaya S, Sakiz D. Lupus erythematosus and lichen planus overlap syndrome:a case report with a rapid response to topical corticosteroid therapy. Dermatol Reports. 2011; 3(3):e48.
Nagao K, Chen KR. A case of lupus erythematosus/lichen planus overlap syndrome. J Dermatol. 2006; 33(3):187-90.
Lospinoso DJ, Fernelius C, Edhegard KD, et al. Lupus erythematosus/lichen planus overlap syndrome: successful treatment with acitretin. Lupus. 2013; 22(8):851-4.
Reynolds TB, Denison EK, Frankl HD, et al. Primary biliary cirrhosis with scleroderma, Raynaud’s phenomenon and telangiectasia. New syndrome. Am J Med. 1971; 50(3):302-12.
David C, Chaigne B, Hollande C, et al. Primary biliary cholangitis and systemic sclerosis (Reynolds syndrome): A casecontrol study. Autoimmun Rev. 2021; 20(7):102842.
Trotta F, Potena A, Bertelli R, et al. Associazione sindrome di Reynolds-sindrome di Sjögren [Reynolds syndrome associated
with Sjögren’s syndrome]. Minerva Med. 1980; 71(19):1385-92. Overlap syndromes in autoimmune connective tissue diseases 69
Thorel JB, Deshayes P. Nécrose digitale révélatrice d’un syndrome de Reynolds (cirrhose biliaire primitive et sclérodermie) avec syndrome de Gougerot-Sjögren. Nouv Presse Med. 1981;10(27):2295-6.
Wollina U, Graefe T, Oelzner P, et al. Pseudoainhum of all fingers associated with Reynolds’ syndrome and breast cancer: report of a case and review of the literature. J Am Acad Dermatol. 2001; 44(2 Suppl):381-4.
Nakamura T, Higashi S, Tomoda K, et al. Primary biliary cirrhosis (PBC)-CREST overlap syndrome with coexistence of Sjögren’s syndrome and thyroid dysfunction. Clin Rheumatol. 2007; 26(4):596-600.
Michaud M, Gaudin C, Brechemier D, et al. Un syndrome de Reynolds révélant un thymome malin [Reynolds syndrome revealing a malignant thymoma]. Rev Med Interne. 2013; 34(3):171-3. French.
Sifuentes Giraldo WA, González-García C, de Las Heras Alonso E, de la Puente Bujidos C. Chondrodermatitis nodularis chronica helicis in a patient with systemic sclerosis associated with primary biliary cirrhosis (Reynolds syndrome): A case report. Eur J Rheumatol. 2014; 1(4):161-163.
Sargın G, Senturk T, Borazan S, Coskun A. Primary biliary cholangitis in patients with systemic sclerosis: Unmasking the true face of Reynold’s syndrome. Egyptian Rheumatologist 2020; 42(1):31-34.
Senear FE, Usher B. An unusual type of pemphigus combining features of lupus erythernatosus. Arch. Dermatol. 1926; 13:761-781.
Beutner EH, Chorzelski TP. Studies on etiologic factors in pemphigus. J Cutan Pathol. 1976; 3(2):67-74.
Bean SF, Lynch FW. Senear-Usher syndrome (pemphigus erythematosus). Immunofluorescent studies in a patient. Arch Dermatol. 1970; 101(6):642-5.
Hobbs LK, Noland MB, Raghavan SS, Gru AA. Pemphigus erythematosus: A case series from a tertiary academic center and literature review. J Cutan Pathol. 2021; 48(8):1038-1050.
Maize JC, Green D, Provost TT. Pemphigus foliaceus: a case with serologic features of Senear-Usher syndrome and other autoimmune abnormalities. J Am Acad Dermatol. 1982; 7(6):736-41.
Jablońska S, Chorzelski T, Blaszczyk M, Maciejewski W. Pathogenesis of pemphigus erythematosus. Arch Dermatol Res. 1977; 258(2):135-40.
Willemsen MJ, De Coninck AL, De Raeve LE, Roseeuw DI. Penicillamine-induced pemphigus erythematosus. Int J Dermatol. 1990; 29(3):193-7.
Ruocco V, Pisani M. Induced pemphigus. Arch Dermatol Res. 1982; 274(1-2):123-40.
Baroni A, Puca RV, Aiello FS, et al. Cefuroxime-induced pemphigus erythematosus in a young boy. Clin Exp Dermatol. 2009; 34(6):708-10.
Lo Schiavo A, Puca RV, Romano F, Cozzi R. Pemphigus erythematosus relapse associated with atorvastatin intake. Drug Des Devel Ther. 2014; 8:1463-5.
Gupta MT, Jerajani HR. Control of childhood pemphigus erythematosus with steroids and azathioprine. Br J Dermatol. 2004; 150(1):163-164.
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