Acute reversible renal failure in acute generalized exanthematous pustulosis

Vincent M. Brandenburg, Christian Kurts, Frank Eitner, Emma Hamilton-Williams and Bernhard Heintz

Department of Nephrology and Immunology, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany Email: vincent.brandenburg{at}post.rwth\|[hyphen]\|aachen.de

Sir,

Acute generalized exanthematous pustulosis (AGEP) is characterized by rapidly evolving, generalized, aseptic non-follicular pustular eruption arising on a widespread oedematous erythema [1,2]. AGEP was introduced to the international literature as distinct clinical entity only in 1980 [3] and it is in >80% of all cases considered to be a special subtype of cutaneous adverse drug reaction [1,2]. Reduced renal function has been described previously in about a third of all cases without further details [1]. In our report we document for the first time in literature acute, reversible glomerular damage in a patient with amoxicillin-induced AGEP.

Case

A 51-year-old, previously healthy Caucasian man was treated with amoxicillin p.o. for 5 days (day 1–5) for suspected sinusitis. On day 4 a diffuse oedematous erythema including trunk and extremities developed acutely and 1 day later multiple pinhead-sized pustules erupted predominantly on the man's back accompanied by generalized pruritus. Amoxicillin was stopped and 50 mg/day prednisolon was administered orally between days 4 and 7 without improvement. Some purpuric lesions emerged on the lower extremities. Upon admission at day 8, blood pressure and heart rate were normal. Axillary temperature was 40.1°C and the patient suffered from severe malaise. Discrete ankle oedema was present. Dermatological examination revealed hundreds of pinhead-sized pustules especially on the trunk emerging from a generalized erythematous eruption. The clinical diagnosis of AGEP was established. Laboratory examination showed hyponatraemia (130 mmol/l) (normal range 135–144), hypocalcaemia (1.93 mmol/l) (2.10–2.60), hypoproteinaemia (49 g/l) (66–83), elevated C-reactive protein (CRP) (194 mg/l) (<5 mg/l) and significant leukocytosis (36.1 g/l) (4.3–10.0) with neutrophilia (94%) and no eosinophilia. Platelet count, liver enzymes, and blood coagulation tests were normal. Serum creatinine levels were elevated to 1.8 mg/dl (0.7–1.2) and BUN was 55 mg/dl (20–50). Mild glomerular proteinuria and microhematuria were present. Examination of urinary sediment showed red blood cell casts and >90% of erythrocytes were dysmorphic. The patient refused renal biopsy. Test for antinuclear antibodies, antineutrophil cytoplasmic antibodies, circulating immune complexes, and cryoglobilins were negative. The antistreptolysin O titer was not elevated. C3-complement level was 0.8 (0.9–1.8) at day 9 and 1.2 at day 11. Cultures obtained from blood samples and pustular swabs were sterile. Upon day 10 the itching sensation disappeared and a widespread cutaneous desquamation occurred. On day 15 the cutaneous eruption had resolved completely without specific therapy. In the interval between days 8 and 15, complete blood count was normalized but eosinophils were now elevated to 14% (<8). CRP levels fell continuously to 11 mg/l and body temperature was normalized since day 12. Hyponatraemia, hypocalcaemia, and hypoproteinaemia were also normalized at day 15. Creatinine levels fell to 1.4 mg/dl at day 9 and have continued to be normal since day 10. Urinary sediment has been free of erythrocytic casts or dysmorphic erythrocytes since day 11. Proteinuria was reduced to normal levels at day 15. After 6 months of follow-up, renal function tests were in normal ranges.

Comment

We present a patient with typical clinical findings and laboratory tests for AGEP, for which amoxicillin is a well-documented causative agent [1,2]. There is, however, no satisfactory hypothesis established yet, why only a small percentage of all patients with cutaneous adverse drug reactions develop AGEP. In several previous studies of patients with AGEP, the liver and kidney were reported to be also affected [1,2,4]. These findings in combination with malaise and severe inflammatory response suggest the presence of multi-organ involvement beyond simple cutaneous drug reaction in AGEP [5]. Concerning kidney function, 32% of patients with AGEP were found to have disturbed renal function in a retrospective analysis [1]. There is, however, no detailed information available in the literature about the nature of renal involvement. Acute interstitial nephritis is a well-established mechanism of adverse renal drug reaction [6]. However, in our patient there was strong evidence for predominantly glomerular renal damage. The exact renal pathology remains unclear, as no biopsy specimen was obtained. In the present case, glomerulonephritic urinary sediment was transient, completely reversible and showed a parallel course to the cutaneous eruptions. Some cases of renal failure in AGEP may find an explanation in concomitant leukocytoclastic vaskulitis (20% of cases [1]), as hypersensitivity vasculitis may affect renal function [7]. Recent data demonstrated an involvement of T cells in the pathogenesis of AGEP, suggesting that renal involvement may be due to a type III or type IV hypersensitivity reaction [8]. A role of drug-specific antibodies has not been demonstrated yet.

In conclusion, our case report is indicative of AGEP being part of a multi-system disease with strong evidence for glomerular involvement.

References

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  8. Britschgi M, Steiner UC, Schmid S et al. T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest2001; 107: 1433–1441[Abstract/Free Full Text]




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