| Abstract|| |
The reported prevalence of systemic lupus erythematosus (SLE) in the general population is 20-150 cases per 100,000 population. The female to male ratio ranges from 7-15:1. An estrogen effect has been suggested by a number of observations for this difference. In children, sex hormonal effects are presumably minimal and, thus, the female to male ratio is 3:1. We report a series of three male patients who presented at the B. P. Koirala Institute of Health Sciences and were diagnosed to have lupus nephritis (LN). This is probably the first case series from Nepal on adult male LN. Male patients with SLE present mainly with renal involvement and seizures rather than photophobia and skin manifestations. The outcome also seems to be more serious in males. Thus, we believe that although male patients with lupus are not commonly seen, the manifestations are life threatening and early detection of the disease will lead to better outcome of these patients.
|How to cite this article:|
Agrawaal KK, Dhakal SS. Systemic lupus erythematosus in males: A case series. Saudi J Kidney Dis Transpl 2014;25:638-42
| Introduction|| |
Systemic lupus erythematosus (SLE) is a chronic, occasionally life-threatening, multi-system disorder.  The prevalence of SLE in the United States is 15-50 per 100,000 population; the highest prevalence among ethnic groups studied is in African Americans. Ninety percent of patients are women of child-bearing age.  The prevalence of SLE is far lower in males than in females, especially after puberty.  Additionally, gender may produce different characteristics in the manifestation of SLE.  The etiology of SLE remains unknown and is clearly multifactorial.  The diagnosis is based on characteristic clinical features and presence of auto-antibodies.  SLE in males is uncommon, and we encountered three such cases in a six-month duration, with the patients carrying a high mortality rate. The diagnosis of SLE was based, in all three reported cases, on the American Rheumatism Association (ARA) criteria, which needs a minimum of four of 11 points to be fulfilled for the diagnosis [Table 1]. 
|Table 1: American Rheumatism Association (ARA) now called as American College of Rheumatology (ACR) criteria for the diagnosis of systemic lupus erythematosus.|
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| Case Reports|| |
A 19-year-old male patient presented in the emergency room with loose stools. This was his third presentation for the same complaints. He was pale looking and had right-sided pleural effusion with minimal ascites along with oral ulcers. His mother had died of lupus nephritis (LN). Other systemic examination revealed no detectable abnormality. Laboratory investigations revealed albuminuria, anemia and right-sided exudative pleural effusion. The 24-h urinary protein was 2.7 g. His anti-nuclear anti-body (ANA) level was 1.80 (normal <1.0 unit/ mL) and the anti-double stranded DNA anti-body (dsDNA) was 290.42 (highly positive). These findings fulfilled 6/11 criteria for the diagnosis of SLE. The patient also had associated hypothyroidism. Detailed work-up for tuberculosis in view of the pleural effusion was negative. Renal biopsy showed World Health Organization (WHO) stage IV LN with high activity and chronicity indices. The complement C3 level was 52 (70-120). He was started on corticosteroids and mycophenolate mofetil along with thyroxine and ramipril. He is on regular follow-up and the 24-h urinary protein when last seen was 0.34 g; the ds DNA was 540 (0-50) and urine analysis showed no active sediment or casts.
A 76-year-old male patient presented in the emergency room with complaints of joint pains, which had made him bedridden for the last three months and had caused a stage III pressure ulcer (national pressure ulcer advisory panel staging). On investigations, there was anemia, albuminuria (3+) and right-sided exudative pleural effusion with elevated serum creatinine level and metabolic acidosis. The ANA level was 1.10 and dsDNA was 103.04 (both above the normal reference range). The joint aspirate was negative for growth of organisms. He fulfilled 6/11 criteria for the diagnosis of SLE (i.e., arthritis, serositis, renal disorder, hematologic disorder, immunologic disorder and positive ANA). He was diagnosed to have LN based on the clinical parameters and required three sessions of hemodialysis. He was started on pulse steroid therapy, following which he developed hospital-acquired infection. Renal biopsy could not be done due to poor general medical condition and the patient expired after 18 days of stay in the hospital.
A 36-year-old male patient presented in the emergency room with complaints of cough and fever of one month's duration. History suggestive of photosensitivity was present. On examination, there was malar rash and right-sided exudative pleural effusion. Laboratory evaluation showed thrombocytopenia and albuminuria along with raised ANA and dsDNA levels. He had an episode of generalized tonic clonic seizures on the second day of hospitalization. He was started on pulse steroids and, because the sputum smear was positive for acid fast bacilli, anti-tuberculous treatment was also started. He fulfilled 8/11 criteria for the diagnosis of SLE, which included malar rash, photosensitivity, serositis, hematologic disorder, renal disorder, neurologic disorder, immunologic disorder and positive ANA. Renal biopsy could not be performed as the patient expired during his stay in the hospital.
| Discussion|| |
SLE is a chronic, occasionally life-threatening, multisystem disorder. Patients suffer from a wide array of symptoms and have variable prognosis that depends upon the severity and type of organ(s) involved.  Females are more commonly affected in SLE; females of many mammalian species are known to mount higher antibody responses than males. Women exposed to estrogen-containing oral contraceptives or hormone replacement have an increased risk of developing SLE.  An estrogen effect is suggested by a number of observations, including the female to male ratio of SLE in the different age groups. In children in whom sex hormonal effects are presumably minimal, the female to male ratio is 3:1. In contrast, the ratio in adults ranges from 7-15:1. In older individuals, the ratio is approximately 8:1. The prevalence of SLE is higher among Asians, Afro-Americans, Afro-Caribbeans and Hispanic Americans compared with Americans of European descent in the United States and among Asian Indians, compared with Caucasians, in Great Britain.  In an earlier study at the B. P. Koirala Institute of Health Sciences, the female to male ratio was found to be 10:1. 
Because of improved detection of mild disease, the incidence of SLE has nearly tripled in the last 40 years.  Men with lupus tend to have a similar frequency of occurrence of renal disease, skin manifestations, arthritis and central nervous system manifestations as women, lesser prevalence of photosensitivity and higher prevalence of serositis, older age at diagnosis and a higher one-year mortality.  Older age, male sex, poverty and low complement levels may also be poor prognostic factors, as was noted in a cohort of North American patients.  In the study that included 1378 patients with SLE, with a median follow-up of 6.1 years, 118 patients died (8.6%). The overall cumulative probability of survival after disease diagnosis at 5, 10, 15 and 20 years was 95%, 91%, 85% and 78%, respectively. Based on a multivariate model, age at SLE diagnosis >50 years (hazard ratio = 5.9; P <0.001) and male gender (hazard ratio = 2.4; P = 0.004) were associated with poorer survival.  The major cause of death in the first few years of illness was active disease (e.g., central nervous system, renal or cardiovascular disease) or infection due to immunosuppression.  In 1999, the SLE patient database at the rheumatology clinic, St. Luke's Hospital, included 62 patients, of whom seven were male, and it was seen that serositis, as the initial manifestation at presentation, was more common in males (29% vs. 2%, P <0.05).  In a review, it was found that male SLE had the same disease spectrum as female SLE, with some distinguishing frequencies of organ involvement. Male SLE has either worse or the same disease severity as female SLE, and may have a less-favorable long-term outcome. Most men with lupus have normal gonadal function.  A review performed on the progression of the disease found that the disease is more severe in women above 40 years of age, male patients and in those with late-onset lupus.  Also, there is an increased incidence of thyroid disease in patients with SLE.  The clinical tendency of male SLE cases has not been fully settled by now because the disease is uncommon. 
We observed a wide array of symptoms in our patients. We also observed high mortality, with infection being the most common cause. One of our patients was diagnosed to have co-existing pulmonary tuberculosis. From this case series, we can see that male SLE is not as uncommon as is thought. Unless we maintain a strong index of suspicion, the disease is generally missed and patients land up at late stages, which is invariably fatal.
Conflict of interest: None to declare
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Dr. Krishna Kumar Agrawaal
Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan