Onset of systemic lupus erythematosus in an elderly man
DOI: 10.32364/2587-6821-2020-4-8-525-528
D.S. Aganov, M.M. Toporkov, I.S. Svintsitskaya, E.N. Tsygan, D.I. Sopova
S.M. Kirov Military Medical Academy, St. Petersburg, Russian Federation
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder with a wide range of clinical and laboratory manifestations which occurs predominantly in young women. The most common age of onset is 20–30 years. However, SLE occasionally occurs after the age of 50 years. The clinical signs of SLE are different from those of a typical disease. As a result, a separate form, SLE in the elderly, was identified. SLE in the elderly often manifests as weight loss, fever, myalgia, arthralgia, pulmonary lesions, serositis, cardiovascular, hemolytic, and hematological disorders. The clinical course of late-onset SLE is usually favorable compared to classic SLE. However, poor survival is reported in these patients compared to early-onset SLE. The causes of death in late-onset SLE are infectious and vascular complications, the adverse effects of hormonal and cytostatic therapies, hematological and comorbid disorders. The authors describe a 67-year-old man with late-ons et SLE. A set of tests verified the diagnosis. Efferent treatment was recommended.
Keywords: late-onset SLE, pericarditis, pleuritis, serositis, Rowell syndrome, efferent therapy, plasmapheresis.
For citation: Aganov D.S., Toporkov M.M., Svintsitskaya I.S. et al. Onset of systemic lupus erythematosus in an elderly man. Russian Medical Inquiry. 2020;4(8):525–528. DOI: 10.32364/2587-6821-2020-4-8-525-528.
Background
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder of unknown origin characterized by the production of a wide range of non-organ-specific autoantibodies to various nuclear components and immune-mediated inflammatory damage of tissues and organs [1].
A variety of clinical presentations and variants is typical for SLE. SLE is thought to affect young women as this disease most often strikes reproductive-age women but can be diagnosed at any age [2]. In the recent decades, more data on patients who develop SLE after age 50 years (late-onset SLE) are available. Published data suggest that late-onset SLE accounts for 2-20% of all cases [3-5]. Late-onset SLE is associated with occult (usually atypical) disease onset and course, no classic butterfly rash, photosensitization, Raynaud’s phenomenon, or kidney disease [4, 6]. This makes difficult verifying the diagnosis and results in late SLE diagnosis (in particular, in little awareness about the specificities of this disease in elderly patients).
The early symptoms of late-onset SLE are weight loss, myalgias, fever, arthralgias, cardiovascular and lung diseases, serositis, hemolytic and immunological disturbances [4]. These symptoms require differential diagnosis with a wide range of diseases, primarily infections and malignancies. E. Karoubi Nordon et al. [7] suggest that the diagnostic criteria for classic SLE cannot be fully applied to late-onset SLE. The result is lately verified diagnosis.
Many studies claim that SLE severity reduces with age [3, 4, 8–11]. Thus, Ho et al. [11] have demonstrated that late-onset SLE is characterized by a mild course and little serious relapses. Aljohani et al. [8] report a reduction in nephritis prevalence (9.3% vs. 21.9% in early-onset SLE).
Meanwhile, elderly and senile patients have a number of somatic comorbidities which are associated with poorer prognosis and treatment tolerability. In addition, a careful analysis of the therapy is required to identify medications that are a potential cause of drug-induced SLE (e.g., beta blockers, procainamide, hydralazine, isoniazid, methyldopa, carbamazepine, sulfanilamides, D-penicillamine, interferon-α, and anti-TNF-α monoclonal antibodies) [12].
Despite a favorable course of late-onset SLE, these patients are characterized by lower survival rate compared to early-onset SLE. The causes of death in elderly SLE patients are infectious and vascular complications, adverse effects of hormonal and cytostatic treatment, hematological malignancies, and comorbidities.
Therefore, age at onset has a significant modifying impact on the clinical presentations, course, response to treatment, and prognosis of SLE. We describe late-onset SLE in an elderly man.
Case report
A 67-year-old man believes himself to be ill from June 2018 when he suddenly experienced a subfebrile temperature. In July 2018, the patient complained of pain in the small joints of the hands, radiocarpal, elbow, and shoulder joints as well as fever (38°C). The patient took non-steroidal anti-inflammatory drugs (NSAIDs). However, NSAIDs were ineffective.
The patients underwent in-hospital examinations and treatment from July 04 to July 23, 2018 (preliminary diagnosis: undifferentiated arthritis). At admission, proximal interphalangeal joint arthritis of the second, third, and fourth fingers, distal tibial edema, and subfebrile temperature were observed. Chest auscultation revealed bronchial breathing and single basal dry crackles in forced expiration. Laboratory tests revealed elevated ESR (25 mm/h) and CRP (65 mg/ml). Infusion therapy and metabolic treatment were performed. After 5 days in the hospital, the patient experienced more severe arthralgias, chest pain when breathing, and high body temperature (39°C). No signs of acute cardiovascular events were detected. Chest X-ray discovered right-sided S8 infiltrative lesions. Antibacterial treatment (moxifloxacin 400 mg daily) was ineffective. Chest CT performed on day 4 of antibacterial treatment revealed left-sided S5, S8, S9, and S10 infiltrative lesions, bilateral hydrothorax (right 15 mm, left 8 mm), and pericardial effusion (11 mm). The signs of subepicardial myocardial damage of the left ventricular posterolateral wall were detected by ECG. No elevations of cardiac enzyme levels were observed. However, acute-phase reactants significantly increased (ESR 50 mm/h, CRP 211 mg/ml). Esophagogastroduodenoscopy, colonoscopy, abdominal and pelvic CT, tumor marker tests were performed. Malignancies, endocrine disorders, tuberculosis, and hematologic cancers were excluded.
On July 23, 2018, the patient was admitted to the Clinics of Faculty Therapy of the Military Medical Academy to verify the diagnosis. At admission, the condition was fair due to intoxication (weight loss 11 kg in 1 month, body temperature 38.8°C), inflammatory joint disease (arthritis of the small joints of the hands, radiocarpal, elbow, and shoulder joints with the hypotrophy of hand and upper limb muscles), lung disease (bronchial breathing and diminished breath sounds in the basal segments, respiratory rate 23/min, saturation 96%), and venous insufficiency (varicose veins of the lower extremities, distal tibial edema). ESR was 23 mm/h while CRP was 94 mg/ml and procalcitonin 1.26 ng/ml. Blood and urine cultures yielded no growth of microorganisms. Urinary indices were within normal ranges. Chest CT performed on July 23, 2018, revealed the increasing accumulation of pleural fluid (right 20 mm, left 15 mm) and pericardial effusion (18 mm) and less lung infiltration. Sinus tachycardia (114 bmp) and diffuse impaired repolarization of the interventricular septum, apex, and lateral wall were detected by ECG. Additionally, perivalvular aortal regurgitation, mitral and tricuspid regurgitation stage 1, reduced global LV systolic function (49%), left ventricular delayed relaxation (due to tachycardia), and the separation of pericardial layers (12 mm behind the posterior wall of the left ventricle and 10 mm behind the right atrium) were revealed by echocardiography. No local abnormalities in cardiac contractility were identified.
Within the first two days, the patient was referred to infectious disease specialist, pulmonologist, cardiac surgeon, thoracic surgeon, tuberculosis specialist, and pyogenic infection and sepsis specialist. Severe (SMART-COP score 2 points) hospital-acquired multisegment (S5, S8, S9, S10) pneumonia of the left lung, respiratory insufficiency stage 2, and cryptogenic sepsis were diagnosed. The patient was prescribed with antibacterial therapy (doripenem, metronidazole, vancomycin), infusions and metabolic therapy, and NSAIDs. However, no improvement was reported after 4 days, i.e., febrile temperature, joint disease, high acute-phase reactants (ESR 50 mm/h, CRP 120 mg/ml), elevated transaminases (ALAT 124.2 U/l, ASAT 126.5 U/l) persisted. Serological testing for the markers for connective tissue diseases detected elevated ANF (1:10,000, fine granular fluorescence) and anti-dsDNA antibodies (58 U/ml) but negative immunoblot ANA (Sm, SS-A, Ro-52, SS-B, Scl-70, PMScl, Jo-1, PCNA, dsDNA, AMA-M2, nucleosomes, histones).
Considering the presence of 4 (serositis, arthritis, elevated ANA and anti-dsDNA antibodies) out of 11 classification criteria for SLE suggested by the American College of Rheumatology as well as SLICC (Systemic Lupus Erythematosus International Collaborating Clinics) Damage Index score of 5, the patient was diagnosed with SLE. Pulse therapy (methylprednisolone 500-500-1,000 mg IV) was performed for 3 days. Then, the patient was prescribed with prednisolone 400 mg daily (0.5 mg/kg/day), azathioprine 50 mg daily, and hydroxychloroquine 400 mg daily. The treatment resulted in the improvement as demonstrated by chest CT (July 30, 2018): no infiltrative lung lesions, both pleural fluid (right 12.5 mm, left 12 mm) and pericardial effusion (3 mm) reduced. Considering persistent right-sided tibial edema, the patient was referred to a vascular surgeon. Lower extremity venous ultrasound was performed. Phlebothrombosis of the left popliteal vein and small saphenous vein (partial recanalization) and chronic venous insufficiency stage 3 were identified. CT angiography revealed massive bilateral pulmonary embolism with the residual blood flow near vascular wall. Hence, the final diagnosis was as follows:
Principal diagnosis: Severe systemic lupus erythematosus, high activity (SELENA-SLEDAI score 11), with the involvement of lungs (pneumonitis, bilateral pleuritis), heart (myocarditis, myocardial dystrophy), joints (arthritis, arthralgias), and muscles (myalgias), fever, immunological disturbances (ANF 1:10,000; anti-ds-DNA antibodies 78 IU/ml).
Complications: Probable antiphospholipid syndrome (phlebothrombosis of the left popliteal vein and small saphenous vein, partial recanalization, chronic venous insufficiency stage 3). Pulmonary embolism, embolism of right segmental (А1, А2, А3, А4, А5, А6, А8, А9, А10) pulmonary arteries, embolism of left segmental (А4, А5, А8, А9, А10) pulmonary arteries. Severe (SMART-COP score 3) hospital-acquired multisegment (S5, S8, S9, S10) pneumonia of the left lung. Respiratory insufficiency stage 1. Cryptogenic sepsis.
Considering the improvement after antibacterial therapy and steroids (as demonstrated by chest CT), pneumonic infiltration was regarded as a coexisted infection and pneumonitis at the beginning of SLE. The lack of antiphospholipid antibodies can be accounted for by the treatment and thrombosis as well.
The total length of in-hospital stay was 24 days. The patient was discharged in the satisfactory condition and recommended with azathioprine 50 mg daily (the dose could be increased to 100 mg after the improvement of liver enzymes), hydroxychloroquine 400 mg daily, and prednisolone 40 mg daily with a gradual further tapering.
Later on, the patient did not seek medical attention. Urinary, complete blood count, and biochemical parameters were within normal ranges. In November 2018, after the examination and treatment in the Clinics of Faculty Therapy of the Military Medical Academy, low activity (SELENA-SLEDAI score 0) was established. Urinary and blood parameters were within normal ranges, CRP 0 mg/ml. Treatment tolerability and treatment response were regarded as satisfactory ones. Chest CT (November 16, 2018) revealed no signs of pulmonary embolism. However, pulmonary fibrotic lesions of both lungs were detected. Neither pleural nor pericardial fluid was identified. Chest CT coincided with pulmonary emphysema. At discharge, the patient was recommended to continue the treatment.
From December 23, 2018, the patient complained of moderately itching single but progressive papules in the décolleté zone after prednisolone dose reduction. No improvement was seen after antihistamines. Urinary, complete blood count, and biochemical parameters were within normal ranges.
On January 23, 2019, the patient was admitted to the Clinics of Faculty Therapy of the Military Medical Academy. At admission, red-brown patches, papules, and placoid desquamation affecting face, scalp, body, back, shoulders, forearms, dorsum of hand, thighs, and tibias were observed. The patient was examined by dermatologist. To verify the diagnosis, skin biopsy was performed. Immunological examination (January 15, 2019) revealed ANF 1:1,2560 (fine granular fluorescence) and anti-dsDNA antibodies (60 IU/ml) but negative immunoblot ANA (Sm, SS-A, Ro-52, SS-B, Scl-70, PMScl, Jo-1, PCNA, dsDNA, AMA-M2, nucleosomes, histones). Urinary indices were within normal ranges. Low WBC count (3.0×109/l) and elevated ESR (35 mm/h) were detected by complete blood count. Moderate SLE exacerbation (skin lesion relapse, leukopenia, SELENA-SLEDAI score 3) was diagnosed. Considering these findings, the patient underwent three cascade filtration plasma exchange for immune correction, detoxication, and improving the sensitivity to methylprednisolone pulse therapy (total dose 3 g). The treatment resulted in the regression of skin lesions. Skin biopsy has demonstrated that histological pattern is typical for Rowell syndrome consisting of erythema multiforme-like lesions associated with SLE.
Hence, the final diagnosis was as follows: SLE, relapsing remitting course, moderate exacerbation, low activity (SELENA-SLEDAI score 3), with the involvement of skin (erythema multiforme, capillaritis), lungs (pulmonary fibrosis, emphysema), and heart (myocardial dystrophy), with hemolytic (leukopenia) and immunological (ANF 1:2,560) disturbances. Respiratory insufficiency stage 0. Possible antiphospholipid syndrome.
Conclusions
We described an atypical SLE onset in an elderly man associated with pneumonitis, polyserositis, intoxication, joint disease, myalgias, skin lesions, hematological and immunological disturbances. Diagnostic search was performed using the entire set of available laboratory and instrumental tests and a multidisciplinary approach to verify the diagnosis. The combination of methylprednisolone pulse therapy and cascade filtration plasma exchange was effective in terms of achieving clinical laboratory remission and minimizing the maintenance dose of steroids [13]. Regular follow-up by a rheumatologist is required to assess disease course and basic treatment tolerability and efficacy.
About the authors:
Dmitriy S. Aganov — Cand. of Sci. (Med.), senior resident of the Clinics of Faculty Therapy, S.M. Kirov Military Medical Academy, 6Zh, Academician Lebedev str., St. Petersburg, 194044, Russian Federation; ORCID iD 0000-0002-5082-9322.
Mikhail M. Toporkov — Cand. of Sci. (Med.), lecturer of the Department of Faculty Therapy, S.M. Kirov Military Medical Academy, 6Zh, Academician Lebedev str., St. Petersburg, 194044, Russian Federation; ORCID iD 0000-0002-7417-7509.
Irina S. Svintsitskaya — Cand. of Sci. (Med.), senior lecturer of the Department of Faculty Therapy, S.M. Kirov Military Medical Academy, 6Zh, Academician Lebedev str., St. Petersburg, 194044, Russian Federation; ORCID iD 0000-0002-1317-8276.
Ekaterina N. Tsygan — Cand. of Sci. (Med.), associate professor of the Department of Faculty Therapy, S.M. Kirov Military Medical Academy, 6Zh, Academician Lebedev str., St. Petersburg, 194044, Russian Federation; ORCID iD 0000-0001-8323-4926.
Dar’ya I. Sopova — student of the 6th course of the 4th faculty, S.M. Kirov Military Medical Academy, 6Zh, Academician Lebedev str., St. Petersburg, 194044, Russian Federation; ORCID iD 0000-0002-0823-6435.
Contact information: Irina S. Svintsitskaya, e-mail: sonirinadoc@mail.ru. Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 30.09.2020, revised 16.10.2020, accepted 29.10.2020.
2. Cervera R., Khamashta M., Hughes G.R.V. The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe. Lupus. 2009;18(10):869–874. DOI: 10.1177/0961203309106831.
3. Alonso M., Martinez-Vazquez F. et al. Late-onset systemic lups erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review. Lupus. 2012;21:1135–1148. DOI: 10.1177/0961203312450087.
4. Boddaert J., Amoura Z., Wechsler B. et al. Late-onset systemic lupus erythematosus: a personal series of 47 patients and pooled analysis of 714 cases in the literature. Medicine (Baltimore). 2004;83(6):348–359. DOI: 10.1097/01.md.0000147737.57861.7c.
5. Tomic-Lucic A., Petrovic R., Radak-Perovic M. et al. Late-onset systemic lupus erythematosus: clinical features, course, and prognosis. Clin Rheumatol. 2013;32(7):1053–1058. DOI: 10.1007/s10067-013-2238-y.
6. Padovan M., Govoni M., Castellino G. et al. Late onset systemic lupus erythematosus: no substantial differences using different cut off ages. Rheumatol Int. 2007;27(8):735–741. DOI: 10.1007/s00296-006-0284-3.
7. Karoubi Nordon E., Hayem G., Mentre F. et al. Letter to the Editor: Late onset systemic lupus erythematosus: A new approach. Lupus. 2007;16:1011–1014. DOI: 10.1177/0961203307077148.
8. Aljohani R., Gladman D., Su J., Urowitz M. Disease evolution in late-onset and early-onset systemic lupus erythematosus. Lupus. 2017;26(11):1190–1196. DOI: 10.1177/0961203317696593.
9. Appenzeller S., Pereira D., Costallat L. Greater accrual damage in late-onset systemic lupus erythematosus: a long-term follow-up study. Lupus. 2008;17(11):1023–1028. DOI: 10.1177/0961203308089695.
10. Mok C., Mak A., Chu W., To C., Wong S. Long-term survival of southern Chinese patients with systemic lupus erythematosus: a prospective study of all age-groups. Medicine (Baltimore). 2005;84:218–224. DOI: 10.1097/01.md.0000170022.44998.d1.
11. Ho C.T.K, Mok C.C., Lau C.S., Wong R.W. Late onset systemic lupus erythematosus in southern Chinese. Ann Rheum Dis. 1998; 57:437–440.
12. Katz U., Zandman-Goddard G. Drug-induced lupus: an update. Autoimmun Rev. 2010;10(1):46–50. DOI: 10.1016/j.autrev.2010.07.005.
13. Kronbichler A., Brezina B., Quintana L.F. Efficacy of plasma exchange and immunoadsorption in systemic lupus erythematosus and antiphospholipid syndrome: A systematic review. Autoimmun Rev. 2016;15(1):38–49. DOI: 10.1016/j.autrev.2015.08.010.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
