Systemic lupus erythematosus (SLE) is reportedly becoming a common condition among Black Africans in the sub-Saharan countries like Nigeria. Generally, clinical evidence of renal disease occurs in approximately half of the cases of SLE at presentation. The severity of the renal involvement determines the morbidity and mortality of the disease. We report the first documented case of lupus nephritis in an 11-year-old boy in South-East Nigeria. The diagnosis was based on the clinical presentation of a malar rash, photosensitivity rash, discoid skin lesion, oral ulcer, hematuria and massive proteinuria with anasarca; renal biopsy histology revealed lupus nephritis class IIB and constitutional symptoms. He is responding slowly and steadily to corticosteroids and oral cyclophosphamide. SLE with renal involvement is not an unusual disease and accessibility to diagnostic facilities may bring a major change in the approach of the disease in the sub-region. Keywords: Lupus nephritis, renal biopsy, systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a multisystem disease of autoimmune origin, with presence of autoantibodies particularly, antinuclear antibodies (ANA), and characterized principally by injury to the skin, kidney, joints, central nervous system and serosal membrane. [1] Renal involvement is a significant cause of morbidity and mortality in pediatric SLE [2] and thus has a major impact on the choice of immunomodulating induction therapy and corresponding response in terms of remission. [3] However, renal biopsy is often indicated to assess the severity of renal involvement that influences the mode of therapy and predicts the prognosis. [3] There is a paucity of literature on lupus nephritis from Nigeria especially from the South-Eastern region of the country, hence the need for this first documented case report. We also review available regional and international literatures.
MP, an 11-year-old boy referred through dermatology clinic to the pediatric nephrology unit of University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, South-East Nigeria with three weeks history of skin lesions and generalized body swelling with oliguria of one week. There were no other urinary symptoms, but there were some unspecified constitutional symptoms like fever preceding the history of the skin lesion. There was history of exacerbation of the skin lesion with transient urticarial-like rash on exposure to intense sunlight when he went to the bush to fetch firewood at the onset of the illness. There was no previous history of similar illness. He had both unorthodox intervention and orthodox treatment in the peripheral hospital without improvement, hence his referral to our center. He was not on any medication, prior to this illness. He was ill looking, with anasarca, mildly pale, significant cervical and axillary lymphadenopathy, axillary temperature was 36.8°C, pulse rate of 116 beats/minute, respiratory rate of 28 breaths/minute and blood pressure of 110/90 mmHg (systolic at 50 th percentile and diastolic at 99 th percentile for age, gender and height). He weighed 34 kg (50 th percentile) and height was 133.5 cm (97 th percentile). There were florid and crusted hypo- and hyper-pigmented macules and papules confluent over the scalp (discoid skin lesion) with butterfly distribution rash on the face (malar rash) and mucosal (nasal and oral) excoriations [Figure 1]. Abdomen was grossly distended with ascites demonstrable by fluid thrill and hepatomegaly of 6 cm below the right costal margin. There were bi-basal fine crepitations (pulmonary edema: No radiological features of bronchopneumonia).
Urine flow rate was 0.6 ml/kg/hour and urinalysis showed massive proteinuria with urine protein to creatinine ratio of 1.25 g/mmol and microscopic hematuria at presentation. He had normal hemoglobin concentration (10 g/dl), normal white blood cell count (5.1×10 9 /L) and differential count (neutrophil 73%, lymphocyte 25%, eosinophil 2%) and platelet count of 218×10 9 /L. The serum electrolytes, urea and creatinine were deranged with mild hyperkalemia (5.6 mmol/L), metabolic acidosis (12 mmol/L), azotemia (38.2 mmol/L), creatinine (149 μmol/L or 1.69 mg/dl) and estimated glomerular filtration rate (GFR) of 56.12 ml/min/1.73m 2 using the Schwartz formula. Total serum protein was 63 mg/dl, albumin 20 mg/dl and globulin 43 mg/dl; serum cholesterol level was elevated (8.4 mmol/L or 324.3 mg/dl). Anti-streptolysin O level was <200 IU/L; LE cell was positive. He tested negative to retroviral screening, and hepatitis B and C viral screening. Liver function test showed elevated liver enzymes, normal bilirubin and alkaline phosphatase levels. Prothrombin time was normal and activated partial thromboplastin time was slightly increased. Abdominopelvic ultrasonography revealed bilaterally enlarged echogenic kidney with caliectatic changes and loss of sinoparenchymal differentiation (grade III nephropathy). There were no facilities for serological investigations in the region and were not readily available in other parts of Nigeria. However, anti-double stranded DNA antibody was done later after six weeks of commencement of therapy and it was negative. Provisional diagnosis of nephrotic syndrome was made, probably secondary to post-infectious causes or connective tissue disease. He was managed with furosemide, nifedipine, antibiotic (augmented penicillin) and hydroxychloroquine, sulfasalazine, fluconazole, mycostatin and sulfosalicylic acid cream for the scalp lesion following joint review with dermatology unit. Oral prednisolone 60 mg/m 2 /day was commenced on the 15 th day of admission and to the work-up for renal biopsy. He had a renal biopsy done on the 30 th day of admission and the histology report confirmed lupus nephritis class IIB (after more than two weeks of steroid); mild mesangial hypercellularity, normal tubules and interstitial space [Figure 2]. Oral cyclophosphamide was added and he was discharged after 31 days of admission.
He has been on regular follow-up (6 visits till date). Prednisolone was reduced to 1 mg/kg/dose after eight weeks of previous dosage. The generalized edema has resolved and proteinuria had markedly reduced to urine protein to creatinine of 0.31. He developed steroid toxicity with moon face and alternate day prednisolone was commenced at a dose of 0.5 mg/kg/day and cyclophosphamide 2 mg/kg/day were continued. Presently, he is on alternate day prednisolone 0.5 mg/kg, losartan (angiotensin converter enzyme inhibitor, an anti-proteinuric agent), and cyclophosphamide and sunscreen lotion and to continue the follow-up in the clinic.
SLE remains an exotic disease in African blacks especially in Nigerian children, although there is an increase in the awareness of the disease. Non-availability of serological diagnostic markers may have contributed to the infrequent, under-diagnosis and under-reporting of the disease in the country. But, SLE is fast becoming a common condition in Nigeria. [3],[4] Adelowo and colleagues studied 1250 rheumatology cases over a six-year period and found that lupus accounted for 66 (5.28%) cases of which 95.5% were females; the age range was 17-55 years with mean age of 33 years. [5] The classical triad in majority of children with SLE is fever, polyarthritis and rash; other common features are oral and nasal septum ulcers, hepatosplenomegaly and lymphadenopathy. [4],[5],[6] Olowu studied 11 children, 7 females and 4 males, with a mean age of 11.2±2.53 years. [4] The commonest non-diagnostic symptom was fever, while lupus nephritis, arthritis and serositis were major manifestations. [4] Our index patient is an 11-year-old boy with renal, mucosal and skin manifestations. Fever was also a prominent feature in this patient. He fulfilled five of the criteria for SLE: malar rash, discoid rash, oral ulcers, photosensitivity and nephritis. [3],[7] Lupus nephritis is the commonest visceral manifestation of SLE and can present as hypertension, nephritic or nephrotic syndrome, acute or chronic renal failure and tubulointerstitial nephritis (TIN). [3],[6],[8],[9] Lupus nephritis has been shown to be the common cause of secondary childhood nephrotic syndrome in Nigeria. [8] Olowu et al., reviewed the etiology of 78 cases of childhood nephrotic syndrome diagnosed by histological findings on renal biopsy over 8 years; 24 cases were of secondary etiology while the rest were idiopathic. [8] Lupus nephritis was the commonest secondary etiology and accounted for 37.5% of childhood nephrotic syndrome in their series. [8] Our index case presented with lymphadenopathy, hepatomegaly, hypertension, elevated plasma creatinine, hematuria and nephrotic syndrome. Although hypo-albuminemia and hyper-cholesterolemia are frequent, [3],[4],[6],[8] our patient had marginally reduced serum albumin level and increased cholesterol level. LE cell was positive but antibodies to double stranded DNA was negative, probably because the patient has been on treatment for 6 months before carrying out the investigation, as the test is usually positive in about 70% of SLE patients with active untreated disease. [5] C3, C4 and C1q complement levels could not be done due to unavailability of the facility in our laboratory services in the country and when it is available, it is unaffordable because of financial constraint. This is a similar challenge encountered by Adelowo and colleagues in their study. [5] Lupus nephritis has been classified by World Health Organization (WHO revised, 1995) based on light microscopic findings, into six histological groups (I-VI) in increasing order of severity. [3],[7],[10] This classification determines management approach and the prognosis, the higher the class, the worse the prognosis. [3],[8],[10] Olowu and others in their study of the clinicopathology of childhood-onset renal SLE, documented predominance of class III and IV diseases lupus nephritis in children. [6] Acute renal failure and renal tubular dysfunction were also associated with severe TIN, which occurred in 91% of the cases. [6] Our index patient had class IIB lupus nephritis (mild mesangial hypercellularity) in a delayed renal biopsy after two weeks of corticosteroid treatment. The outcome of the treatment of lupus nephritis could be varied, although with aggressive treatment, prognosis can be improved. [3],[10] About 20% of cases will progress to end stage renal disease (ESRD) requiring dialysis. [3],[10] In Olowu and colleague’s study with mostly class III and IV disease, they documented a remission rate of 71.4% at end of 12 months, a renal survival rate of 86%, relapse rate of 14.3% and mortality rate of 30%. [2],[8] The outcome however was influenced by misdiagnosis and delayed diagnosis. [8] Response to treatment in our index patient is being monitored via clinical evaluation and urinalysis. The skin lesion has healed leaving hypo-pigmented patches with some degree of photosensitivity. He has maintained normal renal function but still has proteinuria although it is no longer in the nephrotic range.
We conclude that SLE with renal involvement is not an unusual disease in Nigeria especially in the region; accessibility to diagnostic facilities like serological studies, immunosuppressive agents, and monitoring of the blood level of the agent may bring a major change in the approach of the disease in the sub-region.
Source of Support: None, Conflict of Interest: None
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