substantial improvement in survival of people living with hiv has been observed with the introduction of antiretroviral therapy ( art ) in sub - saharan africa .
however , the introduction of art has led to new immune - mediated complications from dysfunction of the recovering immune system , termed immune reconstitution inflammatory syndrome ( iris ) . in patients with cryptococcal meningitis ( cm ) , a very common opportunistic infection in sub - saharan africa ,
iris is a frequent complication that is most often associated with exaggerated inflammatory responses in the central nervous system .
although cm remains the most common cause of adult meningitis in the overall population in sub - saharan africa , there are only a few recognized , reported cases of gastrointestinal ( gi ) involvement with cryptococcus in the literature .
an hiv - infected patient on art with a history of recent cm presented with chronic abdominal pain , thickened ileum , and abdominal lymphadenopathy .
he was initially treated for abdominal tuberculosis ( tb ) but later , he was shown to have a histologically confirmed cryptococcoma in the ileum . the major objective of this case report is to highlight the challenges in diagnosis and management of intra - abdominal cryptococcosis , especially in the setting of recent initiation of art .
a 37 year old hiv - positive male was initially diagnosed and treated for cm in may of 2009 with amphotericin induction therapy for 2 weeks followed by fluconazole 400  mg / day .
he had a protracted hospital course lasting 4 weeks because of persistently high intracranial hypertension despite sterilization of his cerebrospinal fluid , and he , required repeated therapeutic lumber punctures .
he started art ( zidovudine , lamivudine , and efavirenz ) on the 11th june 2009 with a baseline cd4 count of 5  cells/l . at day + 21 of art
, he reported abdominal pain with hypogastric tenderness that was empirically treated as urinary tract infection with a 5  day course of ciprofloxacin , and he noted some improvement . his cd4 count at the time had risen to 29  cells/l . at day + 35 of art ,
his general exam was unremarkable , except for a tachypnea of 28 breaths per minute .
the patient was managed as a possible atypical pneumonia with doxycycline , and his respiratory symptoms improved . however , the abdominal pain persisted intermittently with occasional vomiting . at day + 84 of art and in view of the persistent abdominal pain and an occasional dry cough ,
another chest radiograph was performed to exclude tb , which was also unremarkable . at this time ,
his cd4 was only 14  cells/l , and the hiv-1 viral load was 22,000  copies / ml . he reported 100% adherence to his art , and pill counts verified his adherence . at day + 112 of art , the patient still had similar complaints of abdominal pain and occasional vomiting .
repeat cd4 was 8  cells/l , and the viral load was minimally decreased at 15,475  copies / ml . the patient initially declined an ultrasound - guided biopsy but consented to the procedure at day + 140 of art .
this second ultrasound revealed a thickened ileum up to 6 mm , with adjacent 1  cm lymph nodes .
two biopsy specimens from the lymph nodes demonstrated no abnormality at histology . at day + 168 , the patient still had the same complaints with almost unchanged cd4 of 24  cells/l and viral load of 23,755  copies / ml .
he was presumed to be failing art , possibly due to poor absorptive surface because of the thickened gut wall .
a decision was made to initiate empiric anti - tb treatment for possible gastrointestinal tb .
after one week of tb empiric therapy , the patient presented with an acute abdomen , having signs of focal peritonitis in the right iliac fossa .
an upright abdominal radiograph demonstrated evidence of perforation with free air visible under the right hemidiaphram .
an emergency laparotomy was performed , revealing fecal matter with purulent fluid , adhesions , pneumoperitonium , and intestinal perforation at 10  cm proximal to the ileocecal junction .
the confirmatory histopathology report received 2 weeks later revealed a cryptococcoma in the ileal wall as the cause of the perforation with exuberant inflammation demonstrated by the multinucleated giant cell ( figs . 2 and 3 on hematoxylin and eosin stain and figs . 4 and 5 on periodic acid - schiff stain ) .
the patient 's marked clinical improvement after surgery , the lack of any evidence of cryptococcal infection elsewhere in the body especially in the central nervous system and a well formed granuloma formed the basis for the patient 's continuation with maintenance dose of fluconazole 200  mg / day under observation .
at this point , his tb medications were stopped and he was switched to second line art with subsequent viral suppression . through december 2014 , he continues to remain in care on second line art without any complaints .
we have presented a 37 year old hiv positive male , with a history of recent cm who subsequently developed chronic abdominal pain , eventually manifesting as a cryptococcoma of the ileum .
after treatment for cm and initiating art , he had presented with chronic abdominal pain and low grade fever without diarrhea .
he subsequently developed an intestinal perforation and presented with an acute surgical abdomen requiring bowel resection .
we suspected an iris phenomena , in accordance with the patient presentation shortly after initiation of art , recent history of cm , and exuberant inflammation in the granuloma on histology .
although , the initial immune recovery coupled with falling hiv-1 viral loads is consistent with iris , the subsequent virological failure makes the diagnosis of paradoxical iris less clear . in cryptococcosis ,
ideally , intra - operative cultures would have been performed which could have helped distinguish iris from cryptococcal relapse , based on culture sterility vs. growth , respectively .
cryptococcus organisms can be acquired in the gut primarily through hematogenous dissemination   or less commonly through direct inoculation during paracentesis or via a neurosurgical shunt .
the presentation in these gi cases of cryptococcal infection is usually vague , as seen in our patient , with subacute fevers , constitutional symptoms , asthenia , and anorexia .
virtually every intra - abdominal organ has been reported to be affected by cryptococcal infection .
the diagnosis of gi cryptococcosis requires a high index of suspicion , yet as in this case , clinicians may often initially focus on other common etiologies in immunocompromised persons , such as tb .
although abdominal tb was found to be the most common diagnosis in patients with hiv / aids presenting with chronic abdominal pain and abdominal lymphadenopathy , these studies were conducted predominantly in persons without cryptococcosis . among persons with a known pre - existing opportunistic infection , such as cm , the pre - test probability changes as paradoxical iris enters into the differential diagnosis . in our case ,
the characteristics of granulomas found in hiv - infected persons varies depending on whether or not they are receiving art . in pulmonary cryptococcomas ,
persons not receiving art demonstrate yeast proliferation with a histiocytic response but only minor lymphocytic and neutrophilic components .
conversely , cryptococcal granulomas in persons on art are characterized by the presence of cd4 t cells , greater response of histiocytes , and multinucleated giant - cell formation , as demonstrated in our patient .
there is a paucity of evidenced - based data for the management of cryptococcomas . in our case ,
the initial abdominal lymph node biopsy ( 5 weeks prior to the perforation ) did not reveal a diagnosis .
the question raised is , if we had confirmed the diagnosis of gi cryptococcoma before the perforation , would we have been able to effectively intervene . to answer this question
, it might be important to know if the cryptococcoma were due to iris or cryptococcal relapse .
could the patient have benefited from immunosuppressive therapy to treat iris and perhaps , avoid the perforation , or would more enhanced fungal therapy be needed to eradicate the cryptococcus ?
two case reports have described cryptococcomas due to paradoxical iris ; one in the brain   and the other in the retroperitoneal abdomen . in both cases
, they simply observed the patients but also emphasized the importance of confirming sterility of contents in the cryptococcoma by culture . in a case report by katchanov et al .
, a similar presentation of a central nervous system cryptococcoma was initially treated with antifungals exclusively with radiological worsening until steroids were added to direct therapy at paradoxical iris .
we have previously reported the challenges and dangers of using corticosteroids for cm because they may be contraindicated in cases of fluconazole - resistant cryptococcal relapse .
surgery , corticosteroids , and interferon - gamma have been tried in iris - like cryptococcomas due cryptococcus gattii 
 .
empiric tb therapy , including rifampin , could have induced the metabolism of fluconazole , possibly lowering plasma levels by ~50% . these lower levels may have removed the fungistatic control of the cryptococcus , precipitating the perforation . however , after the surgery , the patient was observed on secondary prophylaxis doses of fluconazole , and he did well . to treat a cryptococcoma in the setting of recent initiation of art , where iris versus relapse can not be determined due to the absence of culture results , treatment with a combination of enhanced antifungal therapy and anti - inflammatory therapy
gi cryptococcosis has been described as a rare occurrence , with only a few published case reports .
we have discussed an hiv - infected patient with profound immunosuppression and recent cm who developed a gi cryptococcoma during initial immune recovery followed by virological failure after initiation of art .
the cryptococcoma was not identified and he developed perforation of the ileum , requiring surgery . we anticipate that with the roll out of art in sub - sahara africa , we are bound to see rare presentations of some of common conditions such as cm .
we recommend that health workers have a high index of suspicion for unusual complications of opportunistic infections in the setting of art - associated iris .
often treatment of iris requires only observation or anti - inflammatory drugs , but the presence of active infection needs to be excluded .
the authors declared no potential conflicts of interest with respect to the research , authorship , and/or publication of this article .
 the introduction of antiretroviral therapy ( art ) may lead to unusual paradoxical and unmasking presentations of opportunistic infections . 
 intra - abdominal cryptococcosis is a rare manifestation of cryptococcus . 
 we present the case of an hiv - infected patient on art , with a history of cryptococcal meningitis who presented with subacute , worsening abdominal pain during immune recovery . 
 this evolved into chronic abdominal pain , with thickened bowel , and abdominal lymphadenopathy , while receiving empiric tuberculosis treatment . at 6-months , he developed intestinal perforation due to a histologically confirmed cryptococcoma . 
Introduction
Case report
Discussion
Conflict of interest