Transcript Infectious Diseases Case Presentation 18 September 2002

Infectious Diseases
Case Presentation
18 September 2002
Dr Zakeya Bukhary, Fellow,
Infectious Diseases
Dr Hail Al-Abdely, Consultant,
Infectious Diseases
First Case
History
• A 19-year-old girl from the Eastern
Province, who was completely healthy
until May 2001 when started to c/o:
– RIF pain and fever associated with
constipation and weight loss
– The pain was colicky and slowly progressive,
moderately severe, non-radiating and not
relieved by analgesics
History
• Fever was on and off with no diurnal
variation and no night sweating or chills
• No nausea or vomiting
• No skin rash or joint pains
• Systemic review: unremarkable
History
• No Hx of TB or contact with TB
patients
• No previous abdominal surgeries
• No drug Hx
• Lives in Dhahran
History
• At the local hospital (DHC), she was found
to have ileocecal mass (5/2001)
• Colonoscopy showed ulcers of the Rt
hemicolon and Bx was consistent with
acute inflammation.
• Started empirically on ciprofloxacin + flagyl
but without response
History
• Colonic biopsy ? Crohn’s.
• Started on oral steroids.
• Has temporary improvement and
gained wt.
• Oct 2001, f/u showed an increase in
the mass size clinically and confirmed
by CT abdomen.
• 27 Oct 2001, laparatomy (at DHC)
showed unresectable mass with
intense inflammation involving the
Rt. hemicolon
• Bx showed necrotizing granuloma
with broad fungal hyphae. Culture
was negative.
• Treated with ABLC and continued
low dose steroid
• On 11 Nov 2002  referred to
KFSH&RC for 2nd opinion
• Pt was clinically unwell but not toxic
• P/E:
– T 38.8ºC
PR 110/min
BP 120/70
RR 20
Wt 49 kg
Ht 158 cm
– Not in distress or jaundiced or cyanosed
– Was pale
– No LN enlargement
– Chest/heart exam  unremarkable
Abd Exam
• Soft, with large, irregular, ill-defined mass
extending from the RUQ to RIF
and umbilical region; mildly tender and
hard.
• Non-palpable liver or spleen
• No ascitis
• B.S. were present
Investigation
WBC 14.0
PMN 80%
No bands
Lymph 20.0%
Eosinophils 1.3%
MCV 78.8 MCH 23.4
Hb 92
Plt 305
ESR 15
Urea 4.9
Cr 96
Na 135
K+ 3.3
ALT 50
ALP 185
PPD skin test –ve
Bil 4 Alb30
CXR  N
CT abdomen
12 November 2001
Differential Diagnosis
D. Dx
•
•
•
•
•
Deep GI mycosis
TB
Actinomycosis
Crohn’s
Lymphoma
Course
• Review of histopath slides from DHC
– showed moderate chronic colitis, no
cryptitis with positive granuloma and
fungal hyphae
• With prominent eosinophilic infiltrate
Pathology
• Pt was spiking high grade Temp
40.0º C
• Started on Ambisome + Tazocin for
possibility of perforation and
superadded bacterial infection
• Pain control, NPO, TPN
• Surgical opinion confirmed that the
mass was non-operable
Course
• 14 Nov 2001
– FNA and True cut Bx to get tissue for
microbiological Dx for c/s
• 17 Nov 2001
– Steroids - methylprednisone 1 mg/kg/d started
Course
• 20 Nov 2001
– Dx of GI mycosis confirmed by culture positive
Basidiobolus ranarum
– IV itraconazole was added
– Ambisome changed to Ampho B to minimize
drug induced hepatitis
Course
• f/u CT scan Abd (20/11/2001):
– showed very impressive response to steroids
+ antifungal (Ampho B + short course of
itraconazole) with regression of the
inflammation and dilatation of the Rt.
hemicolon which has emptied its content and
has partly collapsed.
• Clinically, pt was improving with no
fever and no abd pain
• Started on oral feed
• 11 Dec 2001  discharged on
ketoconazole 600 mg p.o. OD, and
steroids on tapering dose
• In vitro - susceptibility test showed
better inhibitory effect of ketoconazole
which was started orally
CT abdomen
8/4/2002
2/9/2002
Discussion
Basidiobolomycosis
• Introduction
– Classification
– Epidemiology
– Pathogenesis & Clinical Manifestation
– Diagnosis
• Revision of invasive G.I.B.
• Rx
Zygomycetes
Mucorales
(Mucormycosis)
Entomophthorales
(Entomophthoramycosis)
Conidiobolus
Basidiobolus
• Basidiobolus species are
normal inhabitants of soil
throughout the world
• They have been also isolated
from the gut of amphibians and
reptiles
• These fungi cause a chronic
inflammatory granulomatous
disease (Entomophthoramycosis)
• reported in healthy inhabitants of
tropical and subtropical regions
(Africa, Southeast Asia, South
America)
• The mode of transmission of
infection to humans remains
unknown
• Inhalation, ingestion, direct
inoculation and acquisition
secondary to I.M. injection and
insect bites have been postulated
• The disease generally manifested
as subcutaneous lesions
• Visceral involvement and deep
invasive infection either primary or
secondary to subcutaneous
disease, is rare and affects mainly
immunocompromised hosts and
can be fatal.
Nazir et al, Ann Trop Paediatrics 1997;17:161
• Diagnosis depends on
microscopic documentation of
tissue invasion and presence of
typical hyphae of B. ranarum
• In contrast with mucormycosis
no vascular invasion or tissue
infarction or necrosis
• Lesions produced by B. ranarum
are characterized by an acute
and/or chronic inflammation in
association with broad, irregular,
erratically septate hyphae,
surrounded by a distinctive
eosinophilic sheath
• Culture of the fungus is the only
way to identify correctly the
species.
• Immunodiffusion test has been
used in several patients and
claims 100% specificity
specificity and may have a
prognostic value.
Kaufman et al, J Clin Microb 1990;28:9:1887
• The first case described of the infection
was in a pt from Indonesia by Joe et al
in 1956
• Approximately 300 cases (90%
cutaneous) have been reported in the
World Literature, mostly from Tropical
Asia, Africa and South America
• A majority of cases have been in
children under 10 years of age
• In 1994, a healthy 8-year-old boy
reported as a case of invasive
retroperitoneal infection due to
B. ranarum based on histopath
who did not respond to high dose
Ampho B but the mass resolved
completely in 6/52 in response to
K1 saturated solution orally
Ann Trop Paediatrics 1997;17:161
• The 5th case was a 49-year-old lady
who presented with GIB mimicking
Crohn’s disease with no response to
mesalamine and steroids
• Diagnosed histopathologically
• Responded clinically to oral itraconazole
Smilack et al, Gastroenterology 1997;119:250
• In 1996 B. ranarum involving the
rectum was reported from Kuwait,
in a 30-year-old man presented
with PR-bleed and polypoid mass
• Dx confirmed by culture
• Responded to antifungals (Ampho
B + ketoconazole)
Khan et al CID 1998;26:521
Am J Clin Pathol 1999;112:610
• Lyon et al conducted a case-control
study to generate hypotheses
about potential risk factors in the
reported few cases of GIB in AZ,
between 1994 to 1999.
• According to their results they
considered:
–Ranitidine
–Smoking
–Digging earth as of one’s job
• The length of residence in AZ
to be associated significantly
with GIB
• Some factors did not reach
statistical significance, including:
–Steroids
–Use of over-the-counter drugs
–Animal contact
–Eating unwashed vegetables
• One of the cases had a Hx of PICA
daily for years before the Dx of GIB
CID 2001;32:1448
• Currently, there is no means of
preventing this infection or even
identifying those at risk for development
of this disease
• Early detection of the disease seems to
be the best hope of reducing the serious
morbidity and mortality associated with
long-standing disease
• Based on the limited information, it
appears that optional treatment of GIB
combines surgical and medical methods
• Pts should undergo resection and
debridement of all affected tissues;
followed prolonged antifungal Rx
CID 2001;32;1448
• Clinical failures have been described
in association with Ampho B
Mycopathologia 1986;95:101
Am Trop Paed 1997;17:161
CID 1999;28:1244
• Ketoconazole has been shown to be
effective in both in vitro and in vivo
studies
AAC 1984;25:413
• The best choice of antifungal
agent is not clear, but
itraconazole seems to have the
best results
Mycopathologia 1986;95:101
Am J Kidney Dis 1997;29:620
Am J Clin Pathol 1999;112:610
CID 1998;27:663
CID 1999;28:1244
CID 2001;32:1448
• In general Basidiobolus spp
displays low MICs of itraconazole
0.25 g/ml, ketoconazole 0.5 g/ml
JAC 1999;44:557
• MICs of 0.1 – 1.0 g/ml found to
be inhibitory
Rev Inf Dis 1987;9(Suppl 1):S15
End of First Case
Second Case
History
• 52Y/O American white female.
– Told to have pulmonary nodules on CXR
10/9/01and subsequently on CT chest 21/9/01
in the US.
– Totally asymptomatic.
– No Intervention
– Moved to Saudi Arabia with her husband
(work for a Saudi bank) 11/2001
History
• Lived in:
– Arkansas- childhood
– California (1978-1995)
– Scotland (1995-1998)
– Poland (1998-2001)
History
• PMH:
– Hypertension
– Hyperlipidemia
– S/P Hysterectomy & salpingo-opherectomy
1996 for large ovarian cyst.
Meds
• Quinapril 20mg QD
• Indapamide 1.5mg QD
• Simvastatin 40mg QD
History
• Seen in a private hospital in Riyadh
– Clinical evaluation was unremarkable
– PPD: negative
– CT chest 17/1/02
17/1/2002
17/1/2002
17/1/2002
17/1/2002
Differential Diagnosis
What will you do next?
Intervention
• Open-Lung biopsy 6/2/02
– Report
• “Caseating granuloma”.
• Sent for TB culture.
Start 4 drugs anti TB (4 March 2002)
High fever and diffuse skin rash (12 March 2002)
Stop anti TB
Better
Course
• 20 March 2002
– Further stains showed fungus
– Started on fluconazole 400mg QD
– Serologies sent for:
•
•
•
•
Cryptococcal serum antigen, negative
Coccidioides ab, negative
Balstomyces ab, negative
Histoplasma ab, could not be determined
Pathology
11/6/2002
11/6/2002
• D/C fluconazole and start itraconazole 400
mg QD
• Patient did not take it.
28/8/2002
28/8/2002
Histoplasmosis
• Introduction
–Pathogenesis
–C. Fx
–Dx
–Rx
Histoplasmosis
• Histoplasma capsulatum was first
described in 1905.
• It is a thermally dimorphic fungus,
found in soil enriched by droppings of
some birds and bats
• It can remain viable for years in the
soil
Histoplasma capsulatum (filamentous phase)
Pathogenesis
• Hyphal elements of H. capsulatum, are
inhaled into the lungs, where they reach the
alveolar spaces and transform into yeasts
forms
• Following pulmonary infection, organisms
spread through lymphatics to the regional
lymph nodes and hematogenously to other
organs
• In immunocompetent patients
resemble tuberculosis, with
caseating granulomas and necrosis
• Granulomas heal with fibrosis and
can calcify
• Reactive arthritis, pericarditis and
erythema nodosum can present
Clinical
• The degree of exposure and immune
status of the host determines the severity
of the disease
• More than 95% of persons infected are
asymptomatic
• Histoplasmoma: a coin-like lesion in the
lungs
• In symptomatic cases:
– Primary pulmonary histoplasmosis
• Mild self-limiting disease
• Rarely severe with ARDS
– Chronic pulmonary histoplasmosis
• Occurs in a setting of underlying
disease, e.g. COPD
• Subacute recurrent pneumonia
• Associated with apical fibrosis and
cavitation
• In symptomatic cases (cont.):
–Disseminated disease
• Most serious form, usually in
immunodeficient patients with
prolonged fever,
hepatosplenomegaly,
meningoencephalitis, sepsis,
DIC.
Dx
• Tissue Bx stains are highly
sensitive
• Immunodiffusion (more specific less
sensitive ) and complement fixation
(more sensitive less specific) antibody
tests assist in Dx
• Antigen detection by
radioimmunoassays in serum and urine
is highly sensitive and specific in
disseminated disease
• In patients with AIDS who have
disseminated histoplasmosis, elevated
antigen levels are present in the urine in
95% of cases, and in the serum in 80%.
Therapy
• In immunocompetent patients:
itraconazole is the drug of choice
and it is highly effective
• Ampho B has a response rate of
more than 75% in meningeal and
life-threatening histoplasmosis
Dismukes et al, Am J Med 1992;93:489