Late-Onset Familial Systemic Lupus Erythematosus With Lupus Nephritis in an 82-Year-Old Male: A Case Report and Literature Review

Abstract

Systemic lupus erythematosus (SLE) rarely occurs in men of any age. Late-onset SLE (typically after the age of 50) presents special challenges. We report a case of SLE with renal involvement in a very old man. The patient, who was 82 years old, presented with acute kidney injury and a family history of SLE. He was diagnosed with lupus nephritis based on clinical criteria, although no renal biopsy was performed. After starting corticosteroid therapy, his condition improved markedly, with recovery of renal function and resolution of proteinuria and hematuria. The patient’s case is notable for its advanced age and familial context, with a milder form of lupus compared with his relatives. Despite the absence of severe kidney damage, the patient’s treatment with corticosteroids was effective, reflecting the unique and rare nature of this case.

Introduction

Systemic lupus erythematosus (SLE) predominantly affects females in childbearing years, but it can also occur in males and at any age (Lu et al., 2010). The data in the medical literature clearly show that between 4% and 22% of SLE patients in reported lupus populations or lupus series are male (Lu et al., 2010). In studies considering familial aggregations of SLE, the figure rises to 30% (Masi & Kaslow, 1978). SLE is eight to 15 times more common in reproductive-age women than in age-matched men. Before puberty, this ratio is much lower at 2-6:1. After menopause, this ratio again decreases to 3-8:1 (Kamen et al., 2008; Lahita, 1996).

The age at onset has been identified as a factor that modifies the clinical manifestations of SLE. Consequently, the elderly or late-onset may represent a distinct subgroup of SLE (Tang et al., 2011). Late-onset SLE (LSLE) has typically been defined as a disease onset after age 50. More reports have proposed an age of 65 or above (Padovan et al., 2007).

Studies have shown that elderly patients are more susceptible to develop acute kidney injury (AKI; Abdel-Kader & Palevsky, 2009) and elderly patients often present with nonspecific symptoms (Furlong et al., 2023).

The diagnosis of an SLE on the basis of its renal manifestation in an elderly man therefore appears to be a challenge. Through this case report, we discuss this unusual clinical situation.

Case Report

An 82-year-old male was admitted with AKI, presenting with a creatinine level of 262 µmol/L. He reported generalized fatigue, abdominal pain, and dyspnea. His medical history included hypertension and type 2 diabetes. The patient had a familial history of SLE. Indeed, his granddaughter was diagnosed with SLE, with severe multi-organ involvement that led to her death at the age of 9. Subsequently, her mother (the patient’s daughter) was diagnosed with SLE with kidney involvement at the age of 40.

Physical examination of the patient revealed a blood pressure of 130/60 mmHg. He exhibited mucocutaneous pallor, hepatosplenomegaly, and crackling rales on pulmonary auscultation. There were no signs of dry eyes or musculoskeletal pain.

AKI was associated in the patient with positive proteinuria and microscopic hematuria. The initial blood test revealed normocytic anemia, hepatic cholestasis, and hypergammaglobulinemia. Both kidneys were of normal size on ultrasound, containing several bilateral cysts.

An immunological workup was therefore ordered, showing C3 hypocomplementemia, positive direct Coombs test and positive anti-nuclear antibodies (ANA) at a titer of 1:12,800 with positive antinucleosome antibodies, and antihistone antibodies. Tests for anti-neutrophil cytoplasmic antigen antibodies, anti-glomerular basement membrane antibodies, and anti-Scl70 antibodies were negative. Table 1 details the initial biological and immunological assessment of the patient.

Table 1.

Laboratory Characteristics of the Patient at the Disease Onset and After 1 Month of Corticosteroid Therapy

Parameter	At SLE onset	After 1 month of corticosteroids
White blood cell count (4.0-10 k/uL)	8	11
Platelet count (150–450 k/uL)	235	250
Hemoglobin (13.5–18.0 g/dL)	6.0	11.5
Mean corpuscular volume (80–95 fL)	86	87
Gamma GT, IU/L (n.v<50)	171	42
Creatinine (64–104 µmol/L)	262	66
Blood urea nitrogen (2.8–7.2 mmol/L)	25.5	7
Total protein (66–83 g/L)	70	69
Albumin (36.0–48.0 g/L)	26.7	30
γ globulin (8–13.5 g/L)	25.5	14
C3 complement (0.82–1.73 g/L)	0.53	1
C4 complement (0.13–0.46 g/L)	0.15	0.16
Anti-dsDNA (<25 IU/mL)	> 800	-
Proteinuria (<0.5 g/24 hr)	0.7	0.2
Urinary red blood cells (<10 elements/mm3)	700	5

Cardiac ultrasound detected a small pericardial effusion.

The patient met the American College of Rheumatology (ACR) criteria for SLE diagnosis (Hochberg, 1997). Although a renal biopsy was deemed impractical due to the presence of bilateral renal cysts, the diagnosis of lupus nephritis was made clinically.

Given the family history of SLE, a familial SLE diagnosis has been established.

The patient was initiated on corticosteroid therapy at 1 mg/kg/day and was monitored monthly in an outpatient setting with assessments of proteinuria, hematuria, complete blood count, and renal function.

Significant improvement was seen after 1 month of treatment, characterized by improved renal function along with resolution of proteinuria and hematuria. The results of the laboratory parameters after 1 month of corticosteroid therapy are shown in Table 1. The patient has been monitored for 1 year and has not experienced any relapse of his disease.

Discussion

SLE can occur at any age, but its highest incidence occurs during the reproductive years (Lu et al., 2010). In 2% to 20% of cases, SLE appears after the age of 50 (Piga et al., 2023). In this report, we presented the case of an 82-year-old man whose AKI led to a diagnosis of familial SLE.

Reviewing the literature, there is a lack of studies on late-onset or elderly lupus patients, primarily limited to case reports and case series. Furthermore, histopathological findings of late-onset lupus nephritis have seldom been described (Sharma et al., 2023; Urrestarazú et al., 2017).

Patients with LSLE develop the characteristic manifestations of SLE less frequently than those with earlier onset. The onset of LSLE is often insidious, presenting with atypical clinical features, and may be complicated by comorbidities that can obscure important symptoms. As a result, patients with LSLE frequently experience delays in diagnosis (Boddaert et al., 2004; Piga et al., 2023). This observation was noted in our patient, as his main complaints were abdominal pain and dyspnea, and he did not present any skin or joint signs, which are often common in lupus men (Urrestarazú et al., 2017).

LSLE is generally benign, with a notable decrease in the incidence and severity of renal disease and lower rate of renal complications (Boddaert et al., 2004; Kutky & Aloudat, 2018; Rovenský & Tuchynová, 2008). Our patient appears to have presented a milder form of lupus than that of his daughter and granddaughter. Although he experienced lupus-related kidney damage, it was not severe, and his AKI improved rapidly.

In immunological terms, patients with LSLE typically exhibit a lower prevalence of anti-dsDNA, antinucleosome, anti-Sm, anti-RNP antibodies, and lupus anticoagulant positivity. Reports indicate that decreased complement levels, including C3, C4, and CH50, are also less frequently seen in LSLE (Padovan et al., 2007; Piga et al., 2023). In contrast, our patient displayed a distinctly different serological profile, demonstrating positive results for anti-dsDNA, antinucleosome, and antihistone antibodies.

In the context of therapy, due to the higher likelihood of comorbid conditions in LSLE and their correlation with adverse outcomes, it is essential to enhance strategies aimed at preventing or mitigating the effects of these comorbidities. This includes minimizing the use of glucocorticoids to reduce the risks of osteoporosis, diabetes, hypertension, and mood disorders. The frequency of cyclophosphamide and azathioprine usage has been found to be significantly lower in LSLE, suggesting reduced disease activity in this group compared with younger patients. Padovan et al. reported that no immunosuppressive agents were used to treat a group of 30 LSLE patients aged 65 years and older (Padovan et al., 2007; Piga et al., 2023). In the study conducted by Mongkolchaiarunya et al., LSLE patients received less immunosuppressive therapy. Interestingly, the treatment outcomes for LN—including complete, partial, and no renal remission—were comparable between the two groups. However, mortality rates were higher in LSLE patients (Mongkolchaiarunya et al., 2024).

In our patient’s case, considering the clinical presentation of glomerular damage with AKI, proteinuria, and hematuria, along with the inability to perform a renal biopsy, we chose to treat him solely with corticosteroids, as he was an elderly man with comorbidities and we achieved good results.

To the best of our knowledge, this is the first documented case of LSLE in a very old man (above 80 years). The oldest patient reported in the reviewed literature was 79 years old (Urrestarazú et al., 2017). Another unique aspect of this case is that it involved familial SLE, affecting three members of one family. In Tunisia, the prevalence of familial SLE is 11% of all SLE cases, which is among the highest rates globally, particularly when compared with Caucasian populations (Chebbi et al., 2020).

As this is an exceptional case report, it cannot be used to generalize the presentation of SLE in elderly men.

Conclusion

Our case shows that familial LSLE can manifest at a very advanced age in men, remaining relatively mild and not requiring heavy immunosuppressive treatment.

Genetic research within families affected by SLE is vital for deepening our understanding of the genetic and molecular mechanisms underlying the disorder. Such studies may lead to new therapeutic strategies by enabling the development of treatments that specifically target the disease’s pathogenic processes.