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We describe a scrub typhus patient with acute renal failure for whom a diagnosis was made based on
serology as well as immunohistochemical (IHC) staining and an electron microscopic examination (EM) of a
renal biopsy specimen. For our case, we demonstrated by IHC staining and EM that renal failure was caused
by acute tubular necrosis due to a direct invasion of Orientia tsutsugamushi.
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VOL. 46, 2008 CASE REPORTS 1549
FIG. 1. Histopathologic findings for the kidneys from a patient with scrub typhus. (a) Histopathologic findings for the kidneys (hematoxylin and
eosin stain; magnification, 100). Acute tubular necrosis with chronic interstitial nephritis is illustrated. Many atrophic tubules and lumens
containing desquamated epithelial casts (asterisks) are found. (b) Immunofluorescent staining of a kidney (magnification, 100). Positive
immunofluorescent staining is indicated in the tubular structures (arrows). Scattered positive signals are also identified in the vascular structures
(asterisks). (c) Immunohistochemical staining of a kidney (magnification, 100). Positive IHC staining is indicated in the tubular structures, and
scattered positive signals are also identified in the vascular structures. (d) Ultramicroscopic findings of the renal tubular epithelial cells. Many O.
tsutsugamushi (O) cells are seen in the cytoplasm. Many small vesicles (arrows) with an O. tsutsugamushi envelope appear around the degenerated
Orientia coccobacilli (DO). Scale bar, 2.0 m.
tients with scrub typhus present with an eschar at the site of the tubules. These histopathologic findings were suggestive of
mite bite, a maculopapular rash, fever, myalgia, headache, and acute tubular necrosis with chronic tubulointerstitial nephritis.
anorexia (4). The prognosis varies between patients, ranging Several hypotheses have been proposed to explain the mech-
from asymptomatic infection to death. Because scrub typhus anism by which O. tsutsugamushi infection causes acute renal
causes systemic vasculitis, it can cause meningitis, interstitial failure. First, it is assumed that the pathophysiology of acute
pneumonia, acute pulmonary edema, hepatitis, and acute renal renal failure is associated with prerenal azotemia due to renal
failure in untreated cases (6, 7, 8, 9). Hematuria and protein- hypoperfusion in cases of shock or volume depletion. Accord-
uria may occur because of renal invasion in 10 to 20% of ing to Dumler et al., prerenal azotemia is the main pathophys-
patients with scrub typhus. Acute renal failure is not a common iology of renal failure caused by the decrease of effective renal
entity, but it is known to be one of the serious complications blood flow due to increased vascular permeability in patients
seen in patients with scrub typhus, spotted fever, or murine with murine typhus accompanied by systemic vasculitis (1).
typhus (3, 5, 10). Fever, headache, and rash are potential Hypoalbuminemia is commonly noted to occur in patients with
indicators for rickettsial disease and are known to be useful rickettsial disease. This has been reported to be due to the
clues for the diagnosis of scrub typhus (1). However, our pa- leakage of plasma albumin into the perivascular space because
tient visited us with the chief complaint of a prompt deterio- of widespread vascular damage (1). In our case, however, there
ration of renal function without the triad of symptoms of scrub was no clear evidence of decreased blood pressure or other
typhus, including typical skin lesions, fever, and headache. To signs and symptoms suggestive of volume depletion, including
identify the cause of the prompt deterioration of renal func- diarrhea and vomiting. Furthermore, our patient had a normal
tion, a renal biopsy with IHC staining, immunofluorescent range of serum albumin levels. This led to the speculation that
staining, and EM were performed. This established a diagnosis acute renal failure did not occur due to prerenal azotemia in
of scrub typhus. An early recovery was achieved following our patient. Second, disseminated intravascular coagulation
doxycycline treatment. (DIC) is considered another pathophysiological trait of renal
In our case, a renal biopsy showed that the capillary loop and failure. To put this another way, renal failure is caused by
cellularity were normal in the glomerulus. The renal tubules microangiopathy due to thrombosis or coagulation in multiple
underwent multifocal tubular necroses, and foci of some organs of patients with DIC. In our case, however, there were
mononuclear cells were identified in the infiltration of the no notable laboratory findings suggestive of DIC or his-
tubulointerstitium. Tubular epithelial cells underwent degen- topathologic findings suspected to indicate thrombosis. Third,
erative changes and were detached from the basement mem- acute tubular necrosis might cause renal failure because of the
brane (Fig. 1). Epithelial casts were observed in some renal direct invasion of O. tsutsugamushi into a renal parenchyma.
1550 CASE REPORTS J. CLIN. MICROBIOL.
Walker and Mattern (7) and others (10) reported that his- This study was supported by research funds from Chosun University
topathological findings were suggestive of multiple interstitial of 2005.
We declare no commercial interest and do not belong to any asso-
nephritis in patients with renal failure accompanied by murine ciation that might pose a conflict of interest for this work.
typhus. Our patient also had acute tubular necrosis, in which
numerous O. tsutsugamushi coccobacilli were deposited within
his renal tubules, as determined by IHC staining, immunoflu- REFERENCES
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