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Clinical  Management  Issues   2011; 5(3) 95

Clinical Management Issues

IntroduCtIon

An organizative hitch characterized by an 
unintentional delayed communication, did 
not affect the positive clinical evolution of 
a patient, and allowed us to study in depth 
an atypical clinical case in terms of differ-
ential diagnosis. A literature search and the 
discussion among all clinicians which come 
from this clinical presentation enabled us 
to contribute with personal, professional 
knowledge of every specialist, and may rep-
resent a stimulating subject for a debate also 
for readers. Only after writing down this 
contribution, we were finally informed of 
the exact microbiological diagnosis, so that 
we voluntary introduced this short premise. 
When postponing the communication of 

Why do we describe this case
The modern medicine makes use of sensi-
tive and specific laboratories technologies, 
which allow to make important diagnosis 
in short periods of time. But sometimes 
this isn’t true. The late availability of a 
microbiological specimen has allowed to 
establish the clinical features by the defini-
tive diagnosis of atypical mycobacteriosis. 
The treatment for a long period with only 
one carbapenem antibiotic did not affect 
the clinical response of the patient

Corresponding author
Dott. Roberto Manfredi
Infectious Diseases, University 
of Bologna, S. Orsola Hospital
Via Massarenti 11
I-40138 Bologna, Italy
Telephone: +39-051-6363355
Telefax: +39-051-343500
roberto.manfredi@unibo.it

Case report

Abstract
A probable case report of an abdominal botryomycosis has been hypothesized in a patient with a 
stable HIV infection under an effective antiretroviral therapy. Hyperpyrexia, abdominal pain 
and tenderness, and a thickening of small intestinal walls associated with multiple mesenteric 
adenopathies and a peritoneal involvement, prompted an ultrasonography-guided fine needle 
biopsy, and later a laparoscopy-laparotomy which excluded a neoplastic or lymphoproliferative 
disorders, showing only abundant fibrotic and necrotic-steatonecrotic tissue, with sparse 
multinuclear giant cells type Langhans. The prompt response to surgical intervention and a 
treatment with i.v. meropenem alone might be referred to a concurrent gram-negative infection 
of abdominal origin, until a late culture of an atypical Mycobacterium came to our attention 
over one month after the end of hospitalization. An updated literature search is presented and 
discussed, in relationship with the observed, extremely infrequent case reports of botryomycosis 
in different clinical settings.

Keywords: Intrabdominal mass; Peritoneal involvement; Inflammatory signs; Surgical 
treatment; Meropenem; Botryomycosis; Atypical mycobacteriosis
Una “misteriosa” massa intraddominale a eziologia infettiva, in un paziente con infezione da 
HIV controllata. Un “ritardo diagnostico” consente di approfondirne la conoscenza studiando 
una patologia rara
CMI 2011; 5(3): 95-106

1 Department of Infectious 
Diseases, University 
of Bologna, S. Orsola-
Malpighi Hospital, 
Bologna, Italy

2 Department of Pathology 
and Histopathology, 
University of Bologna, S. 
Orsola-Malpighi Hospital, 
Bologna, Italy

3 Department of 
Surgery and Organ 
Transplantation, University 
of Bologna, S. Orsola-
Malpighi Hospital, 
Bologna, Italy

Sergio Sabbatani 1, Roberto Manfredi 1, Benedetta Fabbrizio 2, Antonio Caira 3,  
Fabio Filippo Trapani 1, Giovanni Fasulo 1, Pierluigi Viale 1

A “mysterious” intrabdominal mass 
with infectious origin, in a patient 
with HIV infection under control.  

A “delayed diagnosis” allows  
to enlarge our knowledge,  

by assessing a rare disease

the final microbiological diagnosis to the 
“Discussion” section, we aim to leave some 



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Clinical  Management  Issues   2011; 5(3)96

An intrabdominal-peritoneal mass during HIV infection

time and some “suspense” to the readers too, 
in order to underline the adjunctive diagnos-
tic difficulties potentially descending from 
apparently lacking laboratory data in an 
extremely complicated diagnostic “puzzle”, 
and the need to always maintain an elevated, 
broad spectrum mind in the clinical manage-
ment of “difficult to treat” patients.

Botryomycosis has been described since 
1950s as an uncommon bacterial infection 
mimicking actinomycosis and fungal in-
fections, characterized by one or multiple 
aspecific suppurative-granulomatous foci 
containing sulphur-like granules, usually 
with eosinophilic infiltrates, where in many 
cases either Gram-positive organisms (i.e. 
Staphylococcus aureus, coagulase-negative 
Staphylococci, Streptococcus spp., Bacillus or 
Corynebacterium spp.), or Gram-negative 
organisms (i.e. Escherichia coli, Pseudomonas 
aeruginosa, Proteus or Neisseria spp.), and also 
anaerobe bacteria (including Actinobacillus 
and Peptostreptococcus spp., and Propionibac-
terium acnes), might be cultured: sometimes a 
mixed bacterial flora may be found [1-4].

Actually, after the early observations car-
ried out in animals (especially cattle and 
horses), the term “botryomycosis” has been 
proposed by Rivolta in 1884 [1,5], after 
noticing the “grapelike” appearance of its 
macroscopic lesions, which resembled those 
caused by fungi (hence the suffix “mycosis”). 
Later, Magrou proved the most common 
bacterial origin of botryomycosis, by isolat-
ing S. aureus from pulmonary lesions [6], 
and also demonstrated that the unusual 
histopathological picture of botryomycosis 
was the result of a sort of “symbiotic” rela-
tionship between the inoculum microor-
ganism dose, the virulence of the different 
pathogens, and the immune response of the 
affected host [1,6].

Although primarily considered as a vet-
erinary disease, over one hundred of human 
cases have been described in the past century, 
in form of single reports or small case series. 
The majority of described episodes involved 
mainly skin and skin structures [2,7], and 
more infrequently the thorax and the abdo-
men (the so-called visceral botryomycosis, 
which remains a rare disease, often described 
in the compromised host, although the spe-
cific role of host immune response in the 
pathogenesis of visceral botryomycosis is not 
fully understood) [2,3,8,9]. Possible adjunc-
tive host risk factors associated with both 
cutaneous and visceral botryomycosis in-
clude: diabetes mellitus, cystic fibrosis, mal-

nutrition, alcoholism, HIV infection, major 
or minor trauma, a chronic granulomatous 
disease, and prior surgery [2,8,10-16].

Also the pathogenesis of botryomyco-
sis is not completely known: the process is 
thought to involve a combination of sup-
porting factors including an inciting event 
(i.e. a major or minor trauma, including 
piercing for example), the amount of inocu-
lated microorganisms, the intrinsic virulence 
of infecting pathogens, and the intrinsic host 
susceptibility [1-3,6,16].

Since its first report in humans published 
in 1913 [17], botryomycosis remained dif-
ficult to distinguish f rom actinomycosis 
and fungal diseases, in both cutaneous and 
visceral localizations. When the respira-
tory tract is involved, actimomycosis usually 
has an aspiration origin, while the factors 
prompting botryomycosis have not been 
identified yet, with host factors and foreign 
bodies probably playing some role in its 
pathogenesis [1-3,7,18,19].

A retrospective, historical re-appraisal of 
botryomycosis, may be found in the nar-
ration of the Philoctetes’s diseases by So-
phocles masterpiece [20,21], with reference 
to the long-term granulomatous, non-heal-
ing cutaneous wounds of the Greek hero 
Philoctete, which occurred after a painful 
but not lethal snake (viper) bite at his foot. 
The superinfection of this lesion caused the 
legendary, very prolonged stay at the isle of 
Lesmos of the Greek hero, where Philoctete 
was reclaimed by his companions in order to 
prompt a positive course to the long-lasting 
Troy war [20-22]. The limb lesion of Phi-
loctete was described as a painful and ex-
tremely chronic ulcer, not lethal in its course 
but still present after around one decade, and 
complicated by bleeding and a discharge of 
malodorous and purulent material, so that 
it caused severe functional impotence. Some 
Homer’s commenters interpreted the lesion 
of Philoctete as caused by maduromycosis, 
mycetoma, chromoblastomycosis, and also 
botryomycosis. A comparison between the 
description of the clinical features of Phi-
loctetes’s disease and that of very similar af-
flictions (also called actinophytosis, or bac-
terial pseudomycosis, pyogenic granuloma, 
or granular bacteriosis, in some narrations) 
[1,23] shows a clinical resemblance of bot-
ryomycosis, since each of the considered dis-
eases has a chronic course, may frequently 
affect the extremities, may be caused by an 
initial trauma, may present with ulcers, and 
may discharge purulent-haematic material. 



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Clinical  Management  Issues   2011; 5(3) 97

S. Sabbatani, R. Manfredi, B. Fabbrizio, A. Caira, F. F. Trapani, G. Fasulo et al

As examined by Urso and Farella in their 
1996 contribution on Philoctetes’s disease 
[22], actually botryomycosis is primarily lo-
calized at limbs with cutaneous ulcers, has a 
long-term course in absence of an effective 
treatment, is complicated by purulent and 
sero-hematic discharge, has an anamnestic 
trauma, and a foul odour, but usually it is 
not painful.

Anecdotal cases of primary botryomyco-
sis (especially cutaneous localizations) have 
been reported also in patients without any 
known underlying illness. However, immu-
nocompromised patients as a whole [2,7], 
and especially subjects with an underly-
ing cystic fibrosis [24], those with diabetes 
mellitus [2], and patients with HIV and 
AIDS [8,10,25-32], seem to be more prone 
to develop botryomycosis (in particular its 
visceral form), compared with the general 
population. With regard to life age, episodes 
of botryomycosis have been described from 
infancy to old age.

Aim of our report is to describe a patient 
with a stable HIV infection under an effec-
tive antiretroviral therapy, who developed a 
gross abdominal mass with peritoneal in-
volvement, potentially caused by a visceral 
botryomycosis, as suggested by multiple, 
repeated diagnostic procedures (including 
imaging and histopathology studies), and 
whose aetiology might be attributed to a 
gram-negative pathogen, due to the prompt 
response to a treatment with i.v. meropen-
em alone, after laparotomy and biopsy. A 
comprehensive literature search has been 
performed and discussed, in relationship 
with the observed, extremely inf requent 
case report of possible botryomycosis dur-
ing HIV disease, whose diagnosis has been 
finally modified by the delayed knowledge 
of a microbiological isolation.

CAse report

A 37-year-old homosexual male patient 
was initially diagnosed with HIV infection 
four years ago, and was treated with a power-
ful association antiretroviral therapy shortly 
after his referral to our HIV outpatient clinic 
(7 months later). At that time, the HIV rep-
lication rate proved elevated (as showed by 
plasma HIV-RNA levels of 620,000 copies/
ml), and the patient’s immune defence was 
somewhat compromised (as demonstrated 
by a CD4+ T-lymphocyte count of 254 
cells/µl), so that a treatment with the fixed 

association tenofovir-emtricitabine (200-
300 mg/day), plus the protease inhibitor 
atazanavir (300 mg/day), boostered with 
ritonavir (100 mg/day), was recommended, 
and taken by our patient with optimal adher-
ence and no relevant clinical and laboratory 
adverse events.

The past clinical history of our patient in-
cluded a previous, cured syphilis five years 
before, and a phlemmonous appendicitis 
which required surgery, one year before the 
hospitalization in our Division. An allergy to 
amoxicillin-clavulanate was also reported.

Starting from one month before admis-
sion, our patient complained of an irregu-
lar, elevated hyperpyrexia (up to 40°C of 
body temperature), not responsive to broad 
spectrum empiric antibiotics (mostly be-
ta-lactames and macrolides), and poorly 
responsive to antipyretics too, associated 
with mild abdominal pain and tenderness, 
but in absence of diarrhoea, stipsis, nausea 
and vomiting.

Upon admission, a normal leukocyte count 
was shown (6,560 cells/µl), with a tendency 
towards neutrophilia (81.6%), together with 
an elevated erythrocyte sedimentation rate 
(ESR) (75 mm/hour), significantly elevated 
C-reactive protein levels (20.2 mg/dl), and 
overt increased serum fibrinogen levels (648 
mg/dl), in absence of other relevant labora-
tory abnormalities, when excluding a mod-
erate anaemia (haemoglobin level 10.7 g/dl), 
and elevated ferritin levels (up to 780 mg/
ml). The absolute CD4+ T-lymphocyte count 
raised to 399 cells/µl, while HIV-RNA test-
ed extremely low (370 copies/ml), after a the 
7-month successful antiretroviral treatment 
performed with tenofovir-emtricitabine plus 
atazanavir-ritonavir.

An abdominal ultrasonography, and a 
contrast-enhanced abdominal computer-
ized tomography (CT) study showed a mild 
liver and spleen enlargement, an evident 
ascitic effusion, and focused on a thicken-
ing of several small intestinal loops and the 
related mesenteric tissue, with involvement 
of the adjacent peritoneum, located in the 
left paraumbilical region.

The large majority of all performed 
microbiological investigations tested nega-
tive or not significant in relationship with 
the underlying clinical situation. They in-
cluded: blood, sputum, urine, and stool 
culture, stool search for parasitic diseases 
(including Cr yptosporiudium spp. and 
Clostridium difficile), Widal-Wright serol-
ogy, Histoplasma, Entamoeba, Enterovirus 



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Clinical  Management  Issues   2011; 5(3)98

An intrabdominal-peritoneal mass during HIV infection

and Adenovirus serology, and Cryptococ-
cus neoformans serum antigen search. Signs 
of the previous known syphilis infection 
were retrieved (as demonstrated by a low 
1:320 TPHA titre, with negative trepone-
mal tests), serum Quantiferon test proved 
negative, as well as the intradermal Man-
toux reaction. Only the Epstein-Barr virus 
molecular biology tested positive, by dis-
closing 3,250 genome equivalents/ml, while 
the molecular assay for Cytomegalovirus 
infection proved negative (< 500 genome 

equivalents/ml). All laboratory oncology 
markers proved negative.

An esophagogastroduodenoscopy showed 
an erosive gastritis-duodenitis (in absence 
of Helicobacter pylori infection), and a pan-
colonoscopy with multiple biopsies disclosed 
an aspecific colitis. An ultrasonographic 
heart study showed a mild pericardial effu-
sion, a high-resolution thorax CT scan test-
ed not significant, while a further contrast-
enhanced abdominal TC scan, carried out 
10 days after the first examination, showed 

Figura 1
The microscopic 
examination of the 
abdominal mass 
biopsy shows wide 
areas of steatonecrosis, 
granulation tissue 
and a diffuse, chronic 
inflammatory, 
granulomatous 
reaction, with areas 
of colliquative, non-
caseation necrosis. 
Numerous granulomas 
are apparent. 
Haematoxylin-
eosin stain. Original 
magnification 10×

Figura 2
In the specimen also 
extensive necrotic 
and steatonecrotic 
processes, together 
with granulation 
tissue and a diffuse, 
chronic inflammatory, 
granulomatous reaction 
are recognizable, with 
areas of colliquative, 
non-caseation necrosis. 
Focus on the upper 
area of necrosis. 
Haematoxylin-
eosin stain. Original 
magnification 20×



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Clinical  Management  Issues   2011; 5(3) 99

S. Sabbatani, R. Manfredi, B. Fabbrizio, A. Caira, F. F. Trapani, G. Fasulo et al

a progressively increased amount of ascitic 
fluid, a number of enlarged mesenteric and 
para-aortic lymph nodes (up to 16-18 mm 
of maximum diameter), and a hypodense, 
round intrabdominal mass at the root of me-
senterial branch, primarily compatible with 
a lymphoproliferative origin. A subsequent 
total-body tomoscintigraphy (positron 
emission tomography, or PET), disclosed 
a diffuse and intense hypercaptation of the 
18F-FDG radiocompound at all abdominal 
sites (with a maximum SUV – Standardized 
uptake values – index of 17), especially at 
lower left abdomen, where an intestinal and 
peritoneal involvement were confirmed.

The peritoneal fluid was repeatedly ta-
pered and examined: an elevated protein 
content (5,280 mg/dl) was associated with 
an increased leukocyte count (960 cells/µl), 
composed by 75% lymphocytes, 10% neu-
trophils, and 15% monocyte-macrophages. 
At the microscopic examination, a preva-
lence of phlogistic and necrotic material 
was found (poorly represented granulocytes, 
lymphocytes, and plasmacells, with a pre-
dominant CD3+ T-lymphocyte number, and 
a regular CD4+/CD8+ T-lymphocyte ratio), 
in absence of neoplastic cells. Neither bacte-
ria, nor mycobacteria, nor fungi, or other mi-
croorganisms were observed at Gram stain, 
Ziehl-Nielsen stain, and Grocott stain, and 
all cultures tested repeatedly negative for 

all searchable microorganisms (as well as 
molecular biology probes for Mycobacterium 
tuberculosis and atypical mycobateria).

A lymphoprolipherative disease was 
therefore suspected, due to the underlying 
HIV disease, the positivity of Epstein-Barr 
virus viraemia, and especially the aspect of 
the abdominal-peritoneal lesion at all in-
strumental examinations (ultrasonography, 
contrast-enhanced CT scan, and especially 
the PET scan).

As a consequence, an ultrasonography-
guided biopsy of abdominal wall close to 
the thickened mesenteric tissue was per-
formed, but all microbiological and his-
topathological studies performed on biopsy 
material did not disclose any infectious or 
neoplastic disorder, showing only abundant 
fibrotic and necrotic-steatonecrotic tissue 
only, with sparse multinucleated giant cells 
type Langhans.

Thereafter, an explorative laparoscopy and 
laparotomy was finally deemed necessary 
twenty days after admission, in order to have 
a definite diagnosis and approach a specific 
treatment. Thick, hard, white-grayish mem-
branes involving the parietal peritoneum 
and some intestinal loops which appeared 
conglomerated were seen in the left paraum-
bilical region, close to the peritoneal wall of 
the left hemiabdomen. Once again, all intra-
operative material and many tissue biopsies 

Figura 3
When observing the 
slide with a greater 
magnification, the 
granulomas are 
composed of monocytes, 
epithelioid macrophages 
and numerous 
Langhans’ giant cells. 
Langhans’ giant cells 
have multiple nuclei, 
with a “horse-shoe-
like” configuration. 
Haematoxylin-
eosin stain. Original 
magnification 40×



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Clinical  Management  Issues   2011; 5(3)100

An intrabdominal-peritoneal mass during HIV infection

involving also the colonic wall, proved nega-
tive at all microbiological examinations and 
culture and molecular biology testings for all 
searchable microbial pathogens, while his-
topatological studies demonstrated a diffuse 
granulomatous inflammatory process with a 
non-specific aspect, and a diffuse oedema of 
small intestinal walls. On macroscopic ex-
amination, the fibrotic-adipose tissue showed 
multiple areas of steatonecrosis. Microscopic 
examination disclosed wide areas of stea-
tonecrosis, granulation tissue and a diffuse, 
chronic inflammatory, granulomatous reac-
tion, with areas of colliquative, non-caseation 
necrosis (Figures 1 and 2).

The granulomas were composed of mono-
cytes, epithelioid macrophages and numer-
ous Langhans’ giant cells. Langhans’ giant 
cells have multiple nuclei, with a “horse-
shoe-like” configuration (Figure 3).

When considering the clinical course of 
hospitalization, a first empirical attempt per-
formed with i.v. levofloxacin (500 mg twice 
daily for one week) apparently did not act 
significantly. Later, i.v. meropenem (at 3 g/
day) plus i.v. fluconazole (at 400 mg/day) 
were introduced under the suspicion of a 
bacterial and/or fungal aetiology, but fluco-
nazole was discontinued 10 days later after 
obtaining repeated, negative microscropy 
and culture assays for fungal organisms, 
while i.v. meropenem was carried out at the 
same dosage for two more weeks, and acted 
favourably on both the febrile reaction, and 
all the phlogistic parameters (especially C-
reactive protein, ESR, and serum fibrinogen 
levels, which remained remarkably altered 
since patient’s admission). Notably, both 
hyperpyrexia, and abdominal signs rapidly 
disappeared after laparoscopy/laparotomy 
itself, and especially during the prolonged, 
single-agent antibiotic therapy.

After the explorative laparoscopy/laparot-
omy with multiple biopsies, i.v. therapy with 
meropenem was continued for two further 
weeks, and finally allowed to reach a sta-
ble, complete disappearance of fever and 
all abdominal complaints, together with a 
complete normalization of all inflamma-
tory indexes, so that our patient was dis-
charged without any antimicrobial therapy 
(when excluding the unmodified antiretro-
viral combination treatment). A repeated 
a contrast-enhanced abdominal CT scan 
four weeks after the end of his hospitali-
zation confirmed the complete resolution 
of the acute episodes, with isolated fibrotic 
remnants involving the site of the patho-
logical process.

dIsCussIon

Classically, botryomycosis may present 
with cutaneous or visceral (mainly pulmo-
nary) involvement.

When considering cutaneous botryo-
mycosis, feet, hands, inguinal and gluteal 
areas are the most frequently affected. In-
frequent complications may occur under 
the appearance of subcutaneous invasion, 
or by a local lymph node or bone involve-
ment (osteomyelitis), including also skull, 
mandible, or orbit, as well as tendons and 
muscle [2,33-35]. Cutaneous botryomycosis 
sometimes occurs after skin inoculation of 
microorganisms following trauma, surgery, 
or in presence of foreign bodies (including 
piercing practices), or positioning of medi-
cal devices like a pacemaker or orthopaedic 
biomaterials [7,19,23,33,36]. The majority 
of patients present with skin or subcutaneous 
nodules, but in other cases verrucous lesions 
or non-healing ulcers associated with drain-
ing fistulae may develop, with purulent dis-
charge and the frequent presence of yellow-
ish “grains”, resembling the “sulphur grains” 
typical of actinomycosis [37]. Cutaneous 
lesions have a slow clinical progression, and 
may evolve for several months to years (in 
rare cases). Five episodes complicated by 
fistulisation and deep, bone infection have 
been described in 2006 in men aged over 
70 years, who had their long-term infection 
resolved after extensive surgery and pro-
longed antimicrobial administration [23]. 
A paediatric case presenting with hyperpy-
rexia, elevated inflammatory indexes, and 
an inguinal inflammatory mass associated 
with pruritic papules, evolved in a promi-
nent lymphadenitis, which was successfully 
treated with oxacillin and surgery, which 
material yielded the growth of a S. aureus 
strain, although showed a granulomatous 
process at histopatology examination [38]. 
A single case of muscular botryomycosis of 
the abdominal wall followed visceral surgery, 
and involved primary the rectus abdominis 
muscle [35]. Mucosal involvement (i.e. that 
of nasal septum and tongue, or a more exten-
sive oral-facial involvement) has also been 
infrequently reported [16,39,40], as well 
as conjunctival lesions [41]. Patients with 
HIV infection and AIDS may present with 
multiple pruritic papules on neck, trunk, 
and limbs, difficult to be diagnosed until a 
biopsy is performed [28], or a pyoderma-
like appearance in the genital region (suc-
cessfully treated with dapsone in one case) 
[29], as well as complicated forms including 



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Clinical  Management  Issues   2011; 5(3) 101

S. Sabbatani, R. Manfredi, B. Fabbrizio, A. Caira, F. F. Trapani, G. Fasulo et al

both skin and pulmonary involvement with 
concurrent isolation of S. aureus and Pneu-
mocystis carinii in a patient with full-blown 
AIDS [30]. Only one case with lethal course 
followed an isolated cutaneuos localization 
of botryomycosis, in the setting of a severe 
AIDS-related immunodeficiency [26].

Visceral cases of botryomycosis account 
for a non-negligible portion of referred, 
but usually anecdotal cases, burdened by a 
proportionally greater severity and mortal-
ity rate when compared with cutaneous epi-
sodes. Clinical presentations involving liver, 
spleen, kidney, brain, and prostate have been 
described together with the more frequent 
pulmonary localizations [2,3,7]. Systemic 
symptoms such as fever, fatigue, or weight 
loss, may accompany all forms of visceral 
disease.

In particular, signs and symptoms associ-
ated with pulmonary botryomycosis include 
chronic cough, dyspnoea, haemoptysis, and 
chest pain. Clinical examination may be 
negligible, or demonstrate reduced breath 
sounds or rhonchi, should a consolidated 
parenchyma is of concern. Given the pro-
longed disease duration, lung botryomycosis 
may be mistaken for a mycosis, tuberculosis, 
actinomycosis, or a malignancy (especially 
pulmonary cancer) [4,10,15,42,43]. A lit-
erature search performed by Bersoff-Matcha 
in 1998, allowed to record 7 cases of appar-
ently primary pulmonary botryomycosis, 5 
of them treated with surgery, and responsive 
to a concomitant antibiotic treatment, after 
staining and/or culture positive for either 
Gram-positive organisms (S. aureus, non-
haemolytic Streptococci, Bacillus spp.), or 
Gram-negative bacteria (P. aeruginosa, Ser-
ratia spp., other unidentified Gram-negative 
rods) [3], as initially supposed in our case re-
port. A positive outcome was registered after 
a combined medical-surgical management 
in the large majority of cases [3]. A thoracic 
case of botryomycosis was described with a 
pleural lung mass presentation complicated 
by bone invasion into the thoracic spine and 
two posterior ribs [3]. The cultures tested 
negative for all bacterial, mycobacterial, and 
fungi, as well as for Actinomyces and Nocardia 
spp. Malignancies were excluded through a 
mediastinoscopy and lymph node biopsy and 
examination. No immunological abnormali-
ties were detected, save an absolute CD4+ 
T-lymphocyte count of 290 cells/µl (but the 
patient tested HIV-negative). An extensive 
pulmonary-pleural-spine intervention final-
ly yielded P. aeruginosa, so that a ceftazidime 
treatment was administered postoperatively, 

and continued for a prolonged time. A di-
agnosis of botryomycosis was posed on the 
ground of the appearance of the multiple 
biopsy and surgical specimens, enforced by 
the presence of bright eosinophilic clubs at 
the periphery of granules [3]. Another pri-
mary pulmonary case of botryomycosis com-
plicated by parietal pleural involvement was 
attributed to viridans Streptococci, and was 
cured with surgery plus antibiotic treatment 
[43]. A further case of primary lung bot-
ryomycosis with multiple continuous organ 
involvement (parietal pleura, chest wall, dia-
phragm, liver, and costovertebral junction) 
was successfully treated with a three-month 
long antibiotic therapy, after obtaining the 
diagnosis through a CT-guided biopsy of 
the pulmonary mass [44]. A particular case 
of lung botryomycosis secondary to a for-
eign body aspiration, and cured by the sole 
extraction of the foreign body, without any 
surgical-medical intervention, has been also 
reported [19].

When considering concomitant or un-
derlying disorders in the field of pulmonary 
botryomycosis, Paz et al. reported one pa-
tient whose first manifestations of chronic 
granulomatous disease were represented by 
a lung botryomycosis, thus recommending 
a concurrent evaluation for this underlying 
disease [11]. On the other hand, patients 
with cystic fibrosis are well known to be 
at risk for respiratory botryomycosis, since 
different anatomic and immune defence 
defects, and iatrogenic causes are expect-
ed to support a pulmonary botryomycosis 
[24]. Katzenelsen et al. reported 7 pulmo-
nary cases of botryomycosis, with even 5 of 
7 complicated by a lethal course, despite a 
frequent resort to surgery and antimicrobial 
chemotherapy. A gram-positive (Micrococcus 
pyogenes var. aureus) or a gram-negative (P. 
aeruginosa) aetiology was found in all cases. 
As expected, all episodes of suspected lung 
botryomycosis have to be assessed in a differ-
ential diagnosis process with actinomycosis 
and fungal infections, as well as malignan-
cies [14,15,24,37,43-47].

Only a few cases of visceral botryomy-
cosis have been reported as intrabdominal 
abscesses, but detailed aetiological, clinical, 
and outcome notices were often lacking in 
their short descriptions [2]. When the liver, 
spleen, or kidney are involved, a chronic 
abdominal pain and local tenderness to 
palpation are usually present [33,48], as in 
the patient observed by us. One case of ce-
cal botryomycosis [49], and one episode of 
rectal botryomycosis [47] have been also 



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Clinical  Management  Issues   2011; 5(3)102

An intrabdominal-peritoneal mass during HIV infection

described: the last one responded to eryth-
romycin despite the absence of positive cul-
tures [48]. In these cases, ultrasonography 
and CT scans of the abdomen reveal a mass 
lesion suspicious for an abscess or a malig-
nant process, as in the patient reported by 
us. A fatal case of disseminated visceral bot-
ryomycosis probably caused by P. aeruginosa 
has been described in detail by Winslow 
and Chamblin [50], in an 80-year-old man 
who underwent prostatectomy, and with 
post-mortem examination showing multi-
ple, scattered granules involving the lower 
respiratory tract, the heart, and the urinary 
tract (as the supposed origin of the systemic 
infection), which tested negative for fungi 
and Actinomyces spp., but proved repeatedly 
positive for P. aeruginosa cultures. Botryomy-
cosis complicated by central nervous system 
involvement has been also described, in as-
sociation with dental caries or after oral sur-
gery [33,51,52]; focal neurological deficits, 
seizures, or also a meningeal involvement 
have been reported, as well as a rare, fulmi-
nant episode [33]. A unique case of autoptic 
diagnosis of heart botryomycosis has been 
reported recently by Gupta et al. [53]: in 
this anecdotal case, further botryomycotic 
abscesses involved the lungs and the bone 
marrow, leading to a picture of disseminated 
disease, occurring in absence of an apparent 
immunodeficiency.

From a pathogenetic point of view, a 
concomitant immunodeficiency is known 
to prompt the onset and the progression of 
botryomycosis. Brunken et al. [2] reviewed 
some of the immunologic abnormalities 
possibly retrieved in botryomycosis, and 
also postulated a nonspecific host reaction, 
possibly on a hypersensitivity basis, or the 
establishement of a sort of symbiosis status 
between the infecting organisms and the 
host defences. In one cutaneous case re-
port of the year 1983, a reduced absolute B 
e T lymphocyte count was found, together 
with a blunted response to concanavalin 
A stimulation [2]. In particular, a concur-
rent HIV disease or AIDS is thought to 
be a severe risk factor for a predominantly 
cutaneous [25,26,31,32], but also visceral 
(pulmonary only) botryomycosis [10], with 
the multiple immunologic abnormalities 
of HIV infectious probably implicated in 
its pathogenesis. Ahdoot et al. reported 
the successful treatment of a case of muco-
cutaneous botryomycosis with an atypi-
cal presentation, occurred in a 21-year-old 
HIV-infected Somalian woman followed 

in the pre-HAART era, and attributed to 
a S. aureus infection [25]. Patients infected 
with HIV may present atypical skin lesions 
mimicking those of prurigo nodularis, li-
chen simplex chronicus, varicella-zoster 
virus, or sporotrichosis [8,26], although no 
clear relationship has been demonstrated 
between the severity of immunodeficiency 
(as expressed by the peripheral, absolute 
CD4+ T-lymphocyte count), and the sus-
ceptibility to botryomycosis. Medical and 
combined medical-surgical treatment has 
been successful in the large majority of the 
described cases.

The diagnosis of botryomycosis is usu-
ally based on one or more of the following 
procedures [7,39]: identification of non-
filamentous bacteria in purulent granules 
from draining sinuses or in biopsy speci-
mens, culturing bacteria f rom ulcers or 
exudates in patients with clinical findings 
of botryomycosis, or on histopathological 
basis, after tissue biopsy, in patients with a 
likely clinical picture. Gram staining or sil-
ver nitrate staining (by the Gomori-Grocott 
technique) of the crushed granules is used 
for morphologic assessment. Botryomycosis 
may be distinguished from actinomycosis 
and mycetoma since botryomycosis gran-
ules are of variable size and shape, and may 
reach up to 500 microns in diameter. On the 
other hand, actinomycetes are branching, 
filamentous bacteria ≤ 1 micron in diam-
eter, while fungi responsible for mycetoma 
have hyphae that are at least 2 microns wide. 
These differences may easily drive a correct 
recognition. Microscopic evaluation may be 
combined with routine bacterial, fungal, and 
mycobacterial cultures for definitive diagno-
sis. In addition, tissue specimens submitted 
to histopathological studies may add sig-
nificantly. The histopathologic appearance 
of botryomycosis is usually depicted by a 
central focus of necrosis, surrounded by a 
chronic inflammatory reaction containing 
histiocytes, epithelioid cells, multi-nucleated 
giant cells, and a marked fibrosis [33]. The 
granules seen in botryomycosis usually con-
tain bacteria within an eosinophilic matrix 
containing club like projections. This histo-
logic appearance is commonly referred to as 
the Splendore-Hoeppli phenomenon [3,5-
7,38], although this last feature may not be 
always present [26,41,48], as happened in 
our atypical case report.

Radiological and imaging procedures usu-
ally play a very significant role to evaluate 
the size and the extent of organ involvement, 



©SEEd Tutti i diritti riservati
Clinical  Management  Issues   2011; 5(3) 103

S. Sabbatani, R. Manfredi, B. Fabbrizio, A. Caira, F. F. Trapani, G. Fasulo et al

also in the view of eventual surgical inter-
ventions. Pulmonary lesions may appear as 
a consolidation or a mass lesion, while oth-
er forms of visceral botryomycosis usually 
present as a mass lesion, with no particular, 
distiguishing features, as in the abdominal 
case reported by us.

As a consequence, the clinical differen-
tial diagnosis of either cutaneous or vis-
ceral botryomycosis, includes a very broad 
spectrum of disorders, i.e.: actinomycosis, 
mycetoma, atypical mycobacterial infec-
tion, sporotrichosis, cutaneous leishmaniasis, 
verrucous herpes, cutaneous abscess, nocar-
diosis (on the side of infectious diseases), 
and also Kaposi’s sarcoma and other ma-
lignancies (especially when an underlying 
HIV disease is of concern, as in our case) 
[7,14,16,24,27,37,43-47].

With regard to treatment recommen-
dations, cutaneous botryomycosis requires 
antibiotic administration, and surgical de-
bridement in the majority of cases, since 
the encapsulated abscesses are thought to 
protect the eventual microorganisms from 
the effects of standard courses of antibiotics 
[7,16,23,34,47]; sulphamidic derivatives like 
dapsone acted successfully in isolated cases 
[29]. Antimicrobial therapy alone may be 
sufficient for superficial, limited episodes, 
especially when a bacterial pathogen has 
been identified and a malignancy has been 
excluded. Should Gram-positive pathogens 
are implicated, including S. aureus, cotrimox-
azole, clindamycin, tetracyclines, erythromy-
cin, or beta-lactam derivatives like oxacillin 
may be used (usually by oral route), after 
checking the in vitro susceptibility testing. 
In the event of Gram-negative infections 
including P. aeruginosa, an initial therapy 
with i.v. ceftazidime, ciprofloxacin, aztre-
onam, or a carbapenem (like imipenem or 
meropenem) is recommended; if the isolate 
tests fluoroquinolone-sensitive, a sequential 
therapy with oral ciprofloxacin is suggested. 
For infectious due to other Gram-negative 
organisms (i.e. Proteus spp., Escherichia coli, 
Serratia spp., or others), an i.v. beta-lactam 
derivative, a fluoroquinolone, or a carbap-
enem may be the initial choice, waiting 
for the in vitro sensitivity studies. In our 
case the potential role of a Gram-negative 
pathogen was strongly suggested by the rel-
evant activity played by meropenem, whose 
antibacterial action is primarily directed 
against these bacterial agents. The antibi-
otic selection for Pseudomonas spp. or other 
Gram-negative microbial agents is similar 

to that of cutaneous botryomycosis, but all 
episodes of visceral infection usually require 
several months of therapy to have all signs 
and symptoms of botryomycosis resolved 
(while in our case report a proportionally 
rapid response occurred to combined surgery 
and meropenem administration). There is no 
conclusive evidence about the duration of 
medical therapy of botryomycosis, which is 
usually continued until signs and symptoms 
of infection have resolved. For superficial 
infection, 6 to 8 weeks may be sufficient, 
while subjects suffering from a deep infec-
tion and/or a concurrent immunodeficiency 
may require more prolonged courses. Both 
antimicrobial chemotherapy and a careful 
surgical debridement are strongly recom-
mended for the treatment of cutaneous 
botryomycosis (especially those with deep 
tissue invasion, including muscle or bone, 
for those with delayed recovery, and for im-
munocompromised patients), as well as for 
almost all visceral episodes [7,23], as in our 
case. A resection of the mass often occurs 
prior to diagnosis, given the concern for a 
malignancy in the majority of cases of vis-
ceral localization of botryomycosis.

In the setting of HIV disease and AIDS, 
as to our knowledge only 10 cases have been 
reported until now [8,10,25-32], the large 
majority of them (even nine episodes) with 
isolated or predominant skin involvement, 
with only one lethal case associated with a 
severe form of AIDS [26]. As a consequence, 
one single case of pulmonary disease has 
been described in a patient diagnosed with 
a very advanced form of HIV-related im-
munodeficiency (as expressed by a CD4+ 
lymphocyte count of 8 cells/µl), with cough 
and a blood-streaked sputum, fever, chills, 
shortness of breath, and weight loss, as-
sessed with a chest CT scan and diagnosed 
by a fine needle aspiration percutaneous lung 
biopsy, and attributed to S. aureus infection 
on a microscopical basis only, and success-
fully treated with amoxicillin-clavulanate 
and later with erythromycin [10].

Our suspected case of botryomycosis suc-
cessfully resolved after laparotomy and bi-
opsy, and a prolonged antimicrobial therapy 
with a carbapenem (meropenem) alone, 
might have been the first episode of vis-
ceral (intraabdominal) botryomycosis ever 
described in patients living with HIV. The 
difficult differential diagnosis becomes even 
more cumbersome when an underlying HIV 
disease is present, due to the extremely broad 
spectrum of concomitant and overlapping 



©SEEd Tutti i diritti riservati
Clinical  Management  Issues   2011; 5(3)104

An intrabdominal-peritoneal mass during HIV infection

lare from surgical specimens became finally 
available, so that a diagnosis of abdominal, 
atypical mycobacteriosis was unexpectedly 
confirmed, meropenem was discontinued, 
and a specific, long-term treatment was 
established on a day-hospital basis, with 
associated ethambutol, clarythromycin, and 
rifabutin. Notably, atypical mycobacteriosis 
is also included among possible microbiolo-
gical ethiologies of botryomycosis itself, but 
in our experience all microscopic, culture, 
histopathologic, and even molecular biology 
testings on all available clinical specimens 
resulted repeatedly negative up to 40 days 
after patient’s discharge, and our patient ex-
perienced a prolonged clinical response to 
a single-agent antimicrobial chemotherapy 
performed with meropenem alone (which 
is known to have very limited activity as 
a monotherapy, against mycobacteria as a 
whole). After a further two-month follow-
up, at this time our patient is still under an 
effective and well tolerated oral treatment 
for atypical mycobacteriosis, together with 
its antiretroviral regimen carried out to en-
sure a continued control of the underlying 
HIV disease.

dIsClosure

The Authors declare that they have no 
financial competing interests.

conditions, including for instance bacterial, 
fungal, actinomycotic, tubercular, mycobac-
terial, and also neoplastic, lymphoprolifera-
tive, and dysreactive diseases (as suspected 
and ruled out in the diagnostic workout of 
the presented case) [44-46]. The apparent 
lack of some histopatological hallmarks 
of botryomycosis, like the macroscopic 
eosinophilic granuli, and the microscopic 
Splendore-Hoeppli phenomenon, as well as 
the impossibility to culture organisms and 
to search them with molecular diagnostic 
techniques too, might be also attributed to 
the concurrent HIV infection and its relat-
ed immunological abnormalities, possibly 
modified in their appearance and course 
due to the prompt and effective activity of 
the combination antiretroviral therapy al-
ready administered to our patient, and the 
related, remarkable immune system recov-
ery achieved in the meantime by our patient 
[54]. Moreover, the prompt and durable re-
sponse to a prolonged treatment with a po-
tent, single antibiotic agent primarily active 
against a wide spectrum of Gram-negative 
pathogens could have suggested a potential 
bacterial aetiology of intestinal-abdominal 
origin of our case of intrabdominal infection, 
which remained for a long time with an un-
known microbiological diagnosis.

Only 40 days after patient’s discharge, 
from the microbiology laboratory a delayed 
culture of Mycobacterium avium-intracellu-

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