Prof R. Vanholder Professor of Medicine at the University of Ghent, Belgium, Associate Head of the Nephrology Division of the Ghent University Hospital Ghent, Belgium

 

HISTORY
A 35-year old transplant recipient presents in October 2001 with diffuse lymph node adenopathy. She developed end-stage renal failure in the context of a Lupus Erythematosus Disseminatus, which was diagnosed in 1980. After evolving into lupus nephritis, morphologically typed as membrano-proliferative glomerulonephritis, she needed dialysis first in 1991 and received a successful kidney graft in 1995. Shortly after the transplantation, she developed a ureteral leak, for which the ureter of the transplant kidney was connected to her own left ureter, after nephrectomy of her own left kidney. In that removed kidney, a hypernephroma was found accidentally upon routine morphological examination, apparently without further sequel, in spite of intense follow-up. In 1996, a vascular stent was positioned in the renal artery of the transplant kidney because of stenosis. After that, the patient’s history was uneventful until 2001.

RECENT HISTORY
In February 2001, corticosteroid immunosuppressive therapy was completely stopped, after gradual tapering. In September 2001, the patient developed skin lesions on the legs which were similar to the lesions developed many years previously during flares of her lupus. The lupoid nature of the lesions was confirmed by skin biopsy. Corticosteroids were then restarted again for a short 2-week period while azathioprine (ImuranR) was replaced by mofetyl mycophenolate (CellceptR). The third immunosuppressive agent (NeoralR) was maintained all the time at the same dose and the same adequate serum levels.
In October 2001, the patient developed multiple palpable cervical, supraclavicular and occipital lymph nodes; they were not painful, and some of these nodes had a diameter > 0.5 cm. This evolution was accompanied by a subfebrile status, weight loss, night sweats, general malaise and resistance to erythropoietin.

CLINICAL STATUS AT HOSPITALIZATION
The patient was hospitalized, and upon admission, body temperature was 37°4C. Blood pressure was 150/100 mmHg. Pulmonary and cardiac auscultation were normal. Upon abdominal palpation, no hepato-splenomegaly could be registered. The patient showed no edema. Palpable, non-painful lymph nodes were present as described above.

QUESTION 1: DIFFERENTIAL DIAGNOSIS

BIOCHEMISTRY UPON ADMISSION
The following biochemical results were found upon admission (only relevant information given):
- Sedimentation rate: 85/114 mm
- Hemoglobin: 7.8 g/dL
- Leukocyte count: 7590 cells/mm3
- Phosphorus: 2.6 mg/dL
- Serum creatinine: 1.85 mg/dL (stable versus before)
- CRP: 5.2 mg/dL
- Cyclosporin peak (C2): 547 ng/mL
- Antinuclear factor (ANF): negative
- Hemocultures (bacterial): negative
- Lupus anticoagulans: negative
- Cytomegalovirus IgM: negative
- Cytomegalovirus PCR: negative
- Cryptococcus antigen: negative
- Total lymphocyte count: 188/mm3

QUESTION 2: FURTHER INVESTIGATIONS

LYMPH NODE BIOPSY (1)
This slide shows the crude morphology of a lymph node, without comment: for comments, see next slide.

LYMPH NODE BIOPSY (1)
This slide shows the crude morphology of a lymph node, with as comment: Lymph node loaded with histiocytes (slide 2 of power point review added).

LYMPH NODE BIOPSY (2) – ACID-FAST STAINING
This slide shows the morphology of a lymph node after acid-fast staining, without comments, see next slide.

LYMPH NODE BIOPSY (2)
This slide shows the morphology of a lymph node, after acid-fast staining with as comment: Red: acid-fast rods.

TECHNICAL INVESTIGATIONS: SUMMARY
The results of the performed technical investigations are as follows:
- Ultrasound abdomen: no hepatomegaly – discrete splenomegaly – retroperitoneal: enlarged lymph nodes.
- CT-scan: pathologically enlarged lymph nodes in neck, thorax, mediastinim and retroperitoneum.
- High resolution CT-scan of the thorax: apart from the lymph nodes, no changes; parenchyma preserved in normal condition.
- Excisional biopsy of a cervical lymph node: Ziehl-Nielsen: massive acid-fast rods.
- Bone marrow: positive for acid-fast rods.
- Kidney biopsy: positive for acid-fast rods.
- Hemocultures (BACTEC): positive for acid-fast rods.
- Repeated gastric lavage: negative for acid-fast rods.

QUESTION 3: DIFFERENTIAL DIAGNOSIS

QUESTION 4: THERAPY

CLINICAL EVOLUTION
In the three months that followed the diagnosis, the lymph nodes grew bigger and the patient showed a body weight loss by 10 kg. She remained subfebrile, and CRP rose to 18 mg/dL. Lymphocyte counts fell to an absolute minimum of 60 cells/mm3. In the meanwhile, the results of the antbiogram became available, and it appeared that the infective Mycobacterium was resistant to ethambutol and ofloxacine. These two agents were replaced by rifabutine and clofaminzine. Kidney function deteriorated forcing us to start hemodialysis and at a later stage even to remove the transplanted kidney. As inflammation persisted and the general condition continued to deteriorate, the association of aminoglycosides was considered.

QUESTION 5: THERAPY WITH AMINOGLYCOSIDES

PHARMACOKINETIC CURVE OF AMIKACIN
This slide shows the average pharmacokinetic curve of amikacin blood levels, subsequent to several administrations, showing an appropriate peak as well as through. (slide 5 of powerpoint review added)

QUESTION 6: DURATION OF AMINOGLYCOSIDE TREATMENT