A patient with overlap syndrome: systemic lupus erythematosus, dermatomyositis, and Sjögren’s syndrome – a rare overlapping diseases case report

Introduction and aim. Autoimmune rheumatic diseases are a group of disorders with similar clinical, laboratory and immunological manifestations. Connective tissue diseases include systemic scleroderma, dermatomyositis or polymyositis, Sjögren’s syndrome, rheumatoid arthritis, and systemic lupus erythematosus. If the patient meets the diagnostic criteria for at least two of these diseases and has specific serologic markers, a diagnosis of overlap syndrome is possible. Description of the case. This case describes a 27-year-old man who had a history of paroxysmal fever, night sweats, erythe-ma-like skin lesions on the forearms and lower legs, a feeling of progressive muscle weakness especially in the proximal muscles, and dry mouth. The patient was diagnosed with an overlap syndrome: systemic lupus erythematosus, dermatomyositis, and Sjögren’s syndrome. Conclusion. Overlap syndrome is difficult to treat due to its multisystem nature, requiring a symptomatic therapeutic approach and careful control of medication doses to reduce side effects while controlling disease activity.


Introduction
2][3] Mixed connective tissue disease is a rare autoimmune disease characterized by the presence of anti-RNP antibodies. 4,57][8] Overlap syndrome can be diagnosed if the patient meets at least both diagnostic criteria and has specific serologic markers. 1,3][11] Sjögren's syndrome is a chronic inflammatory autoimmune disease of unknown etiology with ANA> 1:80 and anti-Ro and anti-La antibodies.The disease specif-ically affects the lacrimal and salivary glands with lymphocyte infiltration resulting in impaired function. 12,13ermatomyositis is a rare idiopathic inflammatory myopathy accompanied by dermatitis.Autoimmune mechanisms play a major role in the pathogenesis of dermatomyositis, among which anti-Jo-1, anti-SRP and anti-Mi-2 autoantibodies play an important role. 14,15

Aim
The aim of this study was to present this unique disease entity with typical clinical features, detected in a 27-year-old man.

Description of the case
A 27-year-old Caucasian man, he reported paroxysmal fever, night sweats, erythema-like skin lesions on the forearms and lower legs, a feeling of progressive muscle weakness, especially proximal muscles, and dry mouth, which was confirmed by a physical examination.The appearance of these ailments was associated with the consumption of large amounts of alcohol during sertalinum treatment.
The patient was diagnosed with overlap syndrome: systemic lupus erythematosus, dermatomyositis and Sjögren's syndrome in August 2020.Intravenous methylprednisolone was administered, followed by oral steroids, and cyclosporine when the transaminase levels decreased.The treatment resulted in improvement of the patient's general condition and improvement of the myopathy symptoms.The treatment included pulses of methylprednisolone, followed by continued systemic intravenous steroid therapy, and cyclosporine was added after transaminase levels decreased.After the treatment, the patient felt better and the symptoms of myopathy resolved.On follow-up, leukopenia and thrombocytopenia persisted, responding poorly to the previous treatment.After hematological consultation trepanobiopsy was suggested, but the patient did not agree.After improvement of the patient's condition, he was discharged home with recommendations to follow a liver diet, follow-up examinations were ordered and the patient was declared unfit for work.In treatment, he received 6 pulses of methylprednisolone at 500 mg, then oral prednisone at a dose of 60 mg/d and cyclosporine at a dose of 200 mg/d (body weight 88.7 kg).
On September 25, 2020, he was re-admitted to assess the tolerance and effectiveness of treatment, the concentration of cyclosporine was determined (58.6 ng/ ml) and due to non-therapeutic levels (> 80), the dose of cyclosporine was increased to 250 mg/day, the dose of prednisolone was reduced to 40 mg/day.
The patient was hospitalized in 2022 for parenchymal liver injury.The patient developed hypertension as a result of taking steroid medication.On admission, the patient reported no significant complaints, no signs of muscle weakness, and skin lesions on the hands were still present on physical examination.Chronic myopathic changes were found in the right quadriceps muscle.Recordings from the rectus muscle of the right anterior and tibial right thigh demonstrating electrical silence at rest in the muscles.There is no abnormality in the conduction parameters of the examined nerves.Laboratory tests of alanine aminotransferase were initially 263 U/L, and after two weeks the level dropped to 136 U/L, creatine kinase value was 96 U/L, rheumatolophrenic factor in IgM caliber was 29.4 IU/ml (norm: ≥ 20), gamma glutamyltranspeptidase was initially 204 U/L, and after two weeks decreased to 105 U/L.
Laboratory tests performed showed leukopenia, no thrombocytopenia, hypertransaminasemia with slightly elevated cholestasis parameters.Autoimmune tests revealed the presence of anti-nuclear granular fluorescence antibodies 1: 320 and cytoplasmic fluorescence antibodies 1: 640, in ANA 3 highly positive RNP, SS-A, Sm, Ro-52, ribosomal protein P, complement components normal.After gastrointestinal consultation, it was recommended to consider liver biopsy due to the triple digit transaminase values found in 2020.
In April 2022 there was an attempt to include Mycophenolate Mofetil, but it ended with a 3-fold increase in transaminases (administration stopped).Regular monthly supplementation of vitamin B12 (a 1000 units) was ordered.
With such a therapeutic regimen, the patient's development to date was characterized by marked clinical improvement, which allowed him to significantly improve his functional capacity.The patient was classified as unfit for work.The patient was discharged home with recommendations to follow a liver diet, photoprotection, and to take medications such as prednisone, vitamin B12, proton pump inhibitor, and bisoprolol.A visit to the rheumatology department was scheduled to evaluate disease activity and to continue immunoglobulin treatment.

Discussion
2][3] Identifying patients with overlapping syndromes is important as these patients may require different monitoring and treatment regimens. 1,2Clinically, as seen in this case, the most characteristic symptomatology is the presence of erythema-like skin lesions on the forearms and lower legs, a feeling of progressive muscle weakness, especially proximal muscle weakness, dry mouth and night sweats.Due to the overlap of the abovementioned diseases, the patient was treated with steroids and immunoglobulin infusions.The treatment of the overlap syndrome depends on the symptoms predominant in the clinical picture and involves the treatment of the diseases that are part of it.The results of the study by Balbir-Gurman et al. indicate a relatively high incidence of scleroderma overlap syndrome with Sjgogren's syndrome or myositis, and the overlap of scleroderma with SLE is quite rare, the frequent use of steroids, cyclophosphamide and DMARDs, as well as IVIG in patients with overlapping scleroderma is observed. 3Ramya et al. described a case of a patient with overlapping symptoms of SLE, systemic scleroderma, and secondary Sjögren's syndrome who received immunosuppressive and corticosteroid therapy. 167][18][19][20] Itikyala et al. described a syndrome of overlap between systemic lupus erythematosus and vasculitis associated with a cytoplasmic anti-neutrophil antibody; the patient is doing well after treatment with rituximab, but this entity should be recognized and requires appropriate treatment. 10On the other hand, we describe a rare case of overlap between three diseases: SLE, dermatomyositis and Sjögren's syndrome, which are currently well controlled by treatment with corticosteroids and immunoglobulin infusions, while controlling the patient's general condition.

Conclusion
Due to the multisystem nature of the overlap syndrome, it is difficult to treat.Clarification of each patient's condition can lead to improved patient care.

Table 1 .
Comparison of patient outcomes in disease exacerbation and in remission after intravenous administration of methylprednisolone