Focal Segmental Glomerulosclerosis Associating Kimura Disease

Abstract

Kimura disease presents as a benign subcutaneous mass. Although it principally affects the skin and soft tissues, there is a high prevalence of related renal disease. We report a case of Kimura disease from western Asia, presenting itself as nephrotic syndrome, and this case was seen at a nontransplant kidney presenting with focal segmental glomerulonephritis.

• Eosinophilia
• Focal segmental glomerulosclerosis
• Immunoglobulin E
• Kimura disease
• Nephrotic syndrome

INTRODUCTION

Kimura's disease (KD) was first identified where it was described as “angiolymphoid hyperplasia with eosinophilia (ALHE).” The disease was histologically defined by Kimura, and subsequently has been regarded as a separate clinical entity from ALHE in the Japanese literature.[1&2] It causes slowly growing masses in the head and neck regions that arise in the periauricular area, salivary glands, deep soft tissues, regional lymph nodes (LN) and related muscles.[4] The accompanying kidney involvement frequently results in proteinuria and nephrotic syndrome (NS).[3-8], [11]

CASE REPORT

A 21-year-old male patient presented with widespread edema, masses in the neck region, dyspnea, and decreased production of urine. He was first examined in January 2003 with masses in the preauricular and parotis regions. Excisional biopsy from the mass and lymph node was reported as “ALHE.” Increase in the size of the mass and generalized edema prompted the patient to seek medical help from another medical center, and he was admitted with a preliminary diagnosis of NS. The laboratory analyses were as follows; albumin: 14 g/L, leucocytes: 17.800 [eosinophilia (EO) 28%], the amount of proteinuria in the 24 h urine sample was 6.7 g/day. Renal biopsy was not performed, and the patient was operated upon by plastic surgeons with the aim of removing the mass. Subsequently KD diagnosis was made. The patient was admitted to our unit in order to investigate the etiology of the increase in the dimensions of the mass lesion and edema, with the preliminary diagnoses of NS and acute renal failure. Physical examination findings were as follows: a preauricular mass extending into the left mandibular angle and to temporal and malar regions was detected. There was 4 + soft, pitting edema of the lower extremities. Laboratory examinations were as follows: urea: 136 mg/dL, creatinine: 2.9 mg/dL, albumin: 10 g/L, leucocytes: 20.800 (21% EO). The immunoglobulin (IgG) level was 5.1 g/L (7–16), IgE level was 1987 IU/mL (10–506), and IgA and IgM levels were normal. The C3 was 0.77 g/L (0.9–1.8) and the C4 level was normal. The ASO was 495 IU/mL (0–200), and CRP was 200 mg/L (0–5). When the peripheral blood parameters of the patient were examined, CD 3, CD 4, CD 8, CD16, CD 19, CD 56, and CD 57 levels were within the normal limits. The PPD test was negative and the ratio of CD 4/CD 8 was normal. The volume of the 24-hour urine was 200 cc, creatinine clearance was 3 mL/min, and protein concentration was 696 mg/day. Abdominal ultrasound was normal. The volume load did not respond to diuretics and urine output decreased; furthermore, an increase in urea and creatinine levels was observed. Thus, hemodialysis was begun. After four sessions of hemodialysis, an improvement in renal functions and normal urine output was observed. After the patient began to urinate, proteinuria was detected as 17.3 g/day in the 24-h urine sample. Renal biopsy was performed and focal segmental glomerulosclerosis was diagnosed. The patient started to receive 1 mg/kg/day prednisolone and 5 mg/kg/day cyclosporine. Treatment resulted in rapid remission of nephrotic syndrome and normalization of EO, IgE levels, and preauricular lesion. The patients continued taking 4 mg/kg/day cyclosporine and 10 mg alternate-day prednisolone.

DISCUSSION

The triad of painless masses in the head and neck, increased levels of serum IgE, and EO should always raise the suspicion of KD in Asian men.[10] KD can easily be mistaken for a number of benignant and malignant diseases that arise from salivary glands, lymph nodes, soft tissues, and vascular structures. Since it can cause peripheral EO, it can be confused with parasitic infections and allergic reactions.[9&10]

A significant association between KD and renal diseases, and particularly NS exists.[7] Renal involvement, often in the form of NS, occurs months or years after the onset of mass lesions, or in conjunction with them.[11&12]

The connection between the etiopathogenesis of KD and NS has not yet been elucidated. Some authors have suggested that KD is triggered subsequent to allergic or hypersensitivity reactions, or is the result of an atypical cellular autoimmune reaction. Various bacteria, viruses, parasitic agents, or toxins have been implicated in the immunologic reaction.[12]

The alterations in T lymphocyte immunoregulation due to viral infections and toxins or an IgE-induced type 1 hypersensitivity that mediates lymphokine release were implicated in characteristic lymph node changes and renal involvement.[9] Although T lymphocyte–mediated immunopathogenesis have been proposed, Thomas et al. have obtained normal results in some skin tests (PPD-T, PPD-B, cat scratch skin test) in a patient with mesangioproliferative GLN, and, consequently, these investigators have disagreed with a generalized T lymphocyte disorder.[8] However, in our patient, some of the tests showing the number and function of T lymphocytes were also within the normal limits.

Until 1990, the total number of reported KD cases was 266, and renal involvement was frequent. Proteinuria was detected in 16%, and in 78% of these the level of proteinuria fulfilled the criterion for nephrotic syndrome. Less than 40 of the reported cases underwent biopsy and histological diagnoses were as follows: membranous GLN in 10 patients, mesangioproliferative GLN in eight patients, diffuse proliferative GLN in one patient, FSGS in one patient, and MCD in four patients.[7]

In our literature search, we did not find any large series after 1990. In the previous publications with larger patient series, FSGS was demonstrated in only one patient.[7] The number of patients reported after 1990 is five. In three of these cases with a diagnosis of FSGS and KD, renal transplantation was performed.[3], [11&12] Our case is the third FSGS patient without a history of transplantation after year 1990.

Senel et al. have been able to achieve rapid improvement in KD lesions and renal functions by immunosuppressive therapy (cyclosporine, low dose corticosteroids, and azathioprine) in a patient with KD and FSGS, and have recommended the use of this regimen in FSGS patients with extensive fibrosis and glomerulosclerosis.[11] In a case with KD and FSGS reported by Romao et al., corticosteroid monotherapy was given after the diagnosis of NS. There was a partial remission in proteinuria, but the rapid decline in the renal functions necessitated transplantation.[3] In our patient, we preferred the combined treatment approach on the basis of findings in favor of chronicity, confirmed efficacy of cyclosporine in this patient group, and ineffectiveness of steroid monotherapy.

The prognosis in patients developing NS is closely related to the histopathological type. No differences with regard to the rates of corticosteroid response between the nephrotic syndrome due to KD and the primary renal disease were detected.[7]

We thought it was worth reporting this NS case from Turkey, since it is a rare occurrence in our country. The patient had a typical clinical presentation with characteristic histopathologic features and renal involvement, which is common in the advanced stages. It should always be borne in mind that the patient should be referred to an appropriate medical center after the initial diagnosis is made, owing to the risk of subsequent renal involvement.