| Abstract|| |
A 63-year-old woman presented with severe volume depletion and pre-renal azotemia. She had xerostomia, xerophthalmia and cervical lymhadenopathy. Urine examination revealed proteinuria, hematuria and glycosuria. Laboratory studies, after volume repletion, revealed hyper-gammaglobulinemia. Renal biopsy showed interstitial nephropathy and salivary-gland biopsy showed glandular atrophy and diffuse fibrosis. Diagnosis of leishmaniasis was established by bone marrow examination and serology. The patient was treated with pentavalent antimonial (Glucantime) with an excellent response. The treatment, however, had to be interrupted because of transient nephrotoxicity. After a break of four weeks, the antimonial was reinstituted with no more side effects. Both the sicca syndrome and the nephropathy responded very well to the treatment at nine months follow-up. In this case the presentation of visceral leishmaniasis was atypical, probably because of the partially suppressed immunity. The clue to the diagnosis was the polyclonal hypergammaglobulinemia.
Keywords: Sicca syndrome, Visceral leishmaniasis, Nephropathy.
|How to cite this article:|
Kaaroud H, Mhibik S, Béji S, Moussa F B, Abdallah T B, Maiz H B. Visceral Leishmaniasis in a Patient with Sicca Syndrome and Nephropathy. Saudi J Kidney Dis Transpl 2003;14:526-9
|How to cite this URL:|
Kaaroud H, Mhibik S, Béji S, Moussa F B, Abdallah T B, Maiz H B. Visceral Leishmaniasis in a Patient with Sicca Syndrome and Nephropathy. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2021 Jan 21];14:526-9. Available from: https://www.sjkdt.org/text.asp?2003/14/4/526/32994
| Introduction|| |
Visceral leishmaniasis or Kala Azar is an opportunistic protozoal disease endemic in several countries. This disease is characterized by fever, hepatosplenomegaly and hypergammaglobulinemia and is inevitably fatal if not treated.
Leishmaniasis has been reported as a complicating infection in some immunosuppressed patients such as patients infected by the human immunodeficiency virus (HIV).  Its association with Gougerot Sjogren syndrome has not been reported as yet.
The main treatment of this infection is the antimony derivatives, but their nephrotoxicity make their handling difficult especially in patients with nephropathy.
| Case Report|| |
A 63-year-old woman was referred to our hospital with renal failure. She had a medical history of goiter, xerostomia and xerophthalmia several years ago. The patient presented with a one-month history of anorexia, fever, fatigue and vomiting. Physical examination revealed dehydration, hypotension, right cervical lymphadenopathy, avascular homogenous goiter, proteinuria, hematuria and glucosuria. There was no hepatosplenomegaly. Laboratory tests showed hemoglobin of 110g/L, total leukocyte count 5. 1x10³/mm³, ESR 112 mm/h, potassium 2.8 mmol/L, chloride 114 mmol/L, total proteins 91 g/L, gammaglobulin 25.2 g/L with polyclonal peek and serum creatinine 433.2 µmol/L (creatinine clearance 4.9 ml/mn). The liver transaminases were normal. An abdominal ultrasound showed normal size of kidneys, normal liver and spleen. Salivary gland biopsy showed glandular atrophy and diffuse fibrosis. Renal biopsy showed interstitial fibrosis, cellular infiltration and tubular atrophy. Bone marrow examination showed invasion of macrophages by anastigote leishmania. Anti-leishmanial antibodies were positive to titres of 1/100.
After rehydration and improvement of renal function (serum creatinine came down to 88 umol/L), the patient was given intramuscular pentavalent antimonials (Glucantime) 54 mg/ kg/day. By day 13 of treatment with pentavalent antimonials, moderate impairement of renal function was observed with serum creatinine of 132.6 µmol/L, which improved with withdrawal of treatment. One month later, she received a second course of pentavalent antimonials 54 mg/day for 13 days without side effects. The patient had been also treated for the sicca syndrome with corticosteroids 0.5 mg/day for two months, which was tapered by 10 mg every 15 days over the next three months. Ninety days after admission, the patient was discharged in excellent clinical condition, with serum creatinine at 79.6 µmol/L, gammaglobulin 12 g/L, and antileishmanial antibodies being negative. Over the nine months of follow up, the patient was symptom free and all laboratory tests were normal.
| Discussion|| |
Visceral leishmaniasis is still endemic in some regions of Tunisia and has been reported in some immunosuppressed patients from these areas.  Our patient did not have a previous history of Kala Azar infection but resided in an endemic region. The common underlying diseases associated with leishmaniasis are malignancies, HIV infection, systemic lupus erythematosus and in patients on hemodialysis.  Kala Azar is also recognized in patients receiving immunosuppressive therapy especially renal transplant recipients. , The association with sicca syndrome was described previously in canine leishmaniasis. 
It is suggested that a deficiency in the hosts' immune system rather than micro-organism's virulence factors is responsible for acquiring Kala Azar. Impaired cell-mediated immunity and inhibition of macrophage function may act as predisposing factors.  Immunodeficiency state can facilitate the reactivation of a dormant illness in infected patients or predispose such patients to infection in endemic areas.  Visceral leishmaniasis is characterized in immunocompetent patients by fever, hepatosplenomegaly, pancytopenia and hyper-gammaglobulinemia. The extrahematopoietic forms are more frequent in immunosuppressed patients, and the diagnosis is often not considered in the first place.  Our patient had an incomplete form and bone marrow examination was carried out because of persistent altered general state and hypergammaglobulinemia. The drugs of choice to treat leishmaniasis are antimony derivatives although amphotericin B has been proposed as an alterative treatment in resistant cases.  Although the recommended dosage in normal renal function is well known, the presence of renal impairment makes treatment with pentavalent antimonials difficult and the optimum dosage and duration of treatment is not clearly defined.  Little is known about the pharmacokinetics of pentavalent antimonials in renal insufficiency, and there are no data concerning dosage adjustment in patients on hemodialysis. In renal transplant patients, variable doses were given ranging from 10 to 100 mg/kg/day for 2 to 4 weeks. ,,, We therefore decided, in our patient, to give Glucantime after improvement of renal function at the dose of 54 mg/kg/day. Immunodeficient patients are at risk of relapse and treatment may have to be continued for several weeks or months. 
However our patient received treatment for only two months. The toxicity of pentavalent antimonials is not very clear. Some side effects that are observed include headache, myalgia, fever, dyspepsia and nephrotoxicity. The serious complications are pancreatitis, hepatitis and hemorrhage.  Our patient developed renal function impairment due to cumulative toxic effects, which was reversible when Glucantime was withdrawn. A previous study has reported a poor outcome especially in renal transplant recipients; 33% died of super infection, most often Pseudomonas septicemia, or disseminated intravascular coagulation.  If leishmaniasis is not treated, it is usually fatal. The outcome depends on early diagnosis and treatment which may be delayed because of misleading presentation of the disease, particularly in immunodeficient patients.
| Conclusions|| |
Visceral leishmaniasis should be considered in the differential diagnosis of patients, even with moderate immunodeficiency, who present with fever, hematologic abnormalities or hyper-gammaglobulinemia. Therapy with pentavalent antimonials seems efficient as was seen in our case. Adjustment of dosage is necessary in patients with renal failure and more studies are needed to give specific guidelines about this.
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Department of Nephrology and Internal Medicine, Charles Nicolle Hospital, Tunis