Bilateral adrenal histoplasmosis in a Malaysian tertiary hospital:Report of four cases

Rationale:Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency.Often these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal tissues.Patients concerns:We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal masses.Diagnoses:Bilateral adrenal histoplasmosis.Interventions:Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal treatment.Outcomes:Two patients’adrenal function recovered not requiring any steroid replacement,while 1 patient still requires long-term steroid replacement.Lessons:Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal insufficiency.Usually patients have an exposure to bird droppings,bat guano or soil contaminated with histoplasmosis fungi.Histopathological examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.

Intestinal histoplasmosis in immunocompetent adults

AIM: To present a retrospective analysis of clinical and endoscopic features of 4 cases of immunocompetent hosts with intestinal histoplasmosis(IH).METHODS: Four immunocompetent adults were diagnosed with IH between October 2005 and March 2015 at West China Hospital of Sichuan University. Clinical and endoscopic characteristics were summarized and analyzed retrospectively. GMS(Gomori methenamine silver), PAS(periodic acid-Schiff) and Giemsa staining technique were used to confirm Histoplasma capsulatum(H. capsulatum). The symptoms, signs, endoscopic presentations, radiographic imaging, pathological stain results and follow-up are presented as tables and illustrations.RESULTS: The cases were male patients, ranging from 33 to 61 years old, and primarily presented with nonspecific symptoms such as irregular fever, weight loss, abdominal pain and distention. Hepatosplenomegaly and lymphadenopathy were the most common signs. Endoscopic manifestations were localized or diffuse congestion, edema, ulcers, and polypoid nodules with central erosion involving the terminal ileum, ascendingcolon, transverse colon, descending colon, sigmoid colon and rectum, similar to intestinal tuberculosis, tumor, and inflammatory bowel disease. Numerous yeast-like pathogens testing positive for PAS and GMS stains but negative for Giemsa were detected in the cytoplasm of the histiocytes, which were highly suggestive of H. capsulatum.CONCLUSION: Immunocompetent individuals suffering from histoplasmosis are rarely reported. It is necessary that gastroenterologists and endoscopists consider histoplasmosis as a differential diagnosis, even in immunocompetent patients.

Disseminated histoplasmosis in a 17-year-old Nigerian male patient:A case report

Rationale:Disseminated histoplasmosis is the most severe form of histoplasmosis and often associated with fatal outcomes.Both pulmonary and disseminated forms mimics tuberculosis(TB)and may be misdiagnosed.Patient concerns:A 17-year-old male patient compliant with anti-tuberculosis therapy with complaints of fever,cough productive of thick yellowish sputum,fast breathing,abdominal pain,swelling and jaundice.HIV status was negative.Diagnosis:Disseminated histoplasmosis.Interventions:Antimicrobials including anti-TB therapy,ceftriaxone,gentamicin,azithromycin and ciprofloxacin.Outcomes:He was responding to anti-TB drugs until about 4 and a half months on treatment when he fell ill.Peripheral blood film done 2 days prior to his demise revealed florid yeast like organisms in monocytes with eccentric chromatin suggestive of Histoplasma capsulatum.Lessons:Histoplasmosis can both mimic and coexist with TB and so a high index of suspicion is needed for its diagnosis.

Fatal gastrointestinal histoplasmosis 15 years after orthotopic liver transplantation

We report a case of ileo-colonic Histoplasmosis without apparent respiratory involvement in a patient who had previously undergone an orthotopic liver transplant(OLT) for primary biliary cholangitis 15 years earlier. The recipient lived in the United Kingdom,a non-endemic region for Histoplasmosis. However,she had previously lived in rural southern Africa prior to her OLT. The patient presented with iron deficiency anaemia,diarrhoea,abdominal pain and progressive weight loss. She reported no previous foreign travel,however,it later became known that following her OLT she had been on holiday to rural southern Africa. On investigation,a mild granulomatous colitis primarily affecting the right colon was identified,that initially improved with mesalazine. Her symptoms worsened after 18 mo with progressive ulceration of her distal small bowel and right colon. Mycobacterial,Yersinia,cytomegalovirus and human immunodeficiency virus infections were excluded and the patient was treated with prednisolone for a working diagnosis of Crohn's disease. Despite some early symptom improvement following steroids,there was subsequent deterioration with the patient developing gram-negative sepsis and multi-organ failure,leading to her death. Post-mortem examination revealed that her ileo-colonic inflammation was caused by Histoplasmosis.

Oozing sub-cutaneous masses due to histoplasmosis in a patient from Mali

We presented the case of a 64 year old from Mali who was admitted to the hospital for "oozing sub-cutaneous masses".The diagnosis of African histoplasmosis was established by serology. Several courses of amphotericin B resulted in a cure with sequellae.

Clinical,biochemical and imaging characteristics of adrenal histoplasmosis in immunocompetent patients in a non-endemic area:A case series

Objective:To document the clinical,biochemical and imaging phenotypes of immunocompetent patients with adrenal histoplasmosis.Methods:The clinical,biochemical and radiologic data of 18 immunocompetent patients[age:45.00(39.25,56.25)years,median(IQR),m/f(16/2)]with adrenal histoplasmosis presenting in the Department of Endocrinology,BSMMU between 2014 and 2020 were retrospectively analyzed.Results:All patients were seronegative for HIV infection,and 27.8%(5/18)had well controlled diabetes mellitus.The median duration of the symptoms was 6.00(IQR:4.00,11.25)months.All had significant weight loss,anorexia and weakness.Fever was present in 61.1%(11/18)patients and night sweat was present in 27.8%(5/18)cases.Hypotension and hyperpigmentation were present in 55.6%(10/18)and 66.7%(12/18)cases,respectively.Three of 18 patients presented with adrenal crisis.Hyponatremia occurred in 55.6%(10/18)cases,but none had hyperkalemia.Thirteen of 18 patients had adrenal insufficiency whereas 83.3%(15/18)had high adrenocorticotropic hormone.CT scan revealed bilateral adrenal enlargement in all cases with oval shape and regular margin.All were hypodense having radiodensity 21-90 hounsfield unit,and 11.1%(2/18)were heterogeneous in contrast enhancement.None had noticeable calcification whereas 1.1%(2/18)cases had central necrosis with peripheral rim enhancement.Hepatomegaly was present in 6 cases,splenomegaly in 3 cases and 5 patients had abdominal lymphadenopathy.Histoplasmosis were confirmed by positive fine needle aspiration cytology of adrenal tissue.Conclusions:Adrenal histoplasmosis should be considered in the list of differentials of bilateral adrenomegaly in immunocompetent individuals even living in non-endemic areas.

Gastrointestinal histoplasmosis complicating pediatric Crohn disease:A case report and review of literature

BACKGROUND Infection with Histoplasma capsulatum(H.capsulatum)can lead to disseminated disease involving the gastrointestinal tract presenting as diffuse abdominal pain and diarrhea which may mimic inflammatory bowel disease(IBD).CASE SUMMARY We report a case of 12-year-old boy with presumptive diagnosis of Crohn disease(CD)that presented with several months of abdominal pain,weight loss and bloody diarrhea.Colonoscopy showed patchy moderate inflammation characterized by erythema and numerous pseudopolyps involving the terminal ileum,cecum,and ascending colon.Histologic sections from the colon biopsy revealed diffuse cellular infiltrate within the lamina propria with scattered histiocytic aggregates,and occasional non-necrotizing granulomas.Grocott-Gomori’s Methenamine Silver staining confirmed the presence of numerous yeast forms suggestive of Histoplasma spp.,further confirmed with positive urine Histoplasma antigen(6.58 ng/mL,range 0.2-20 ng/mL)and serum immunoglobulin G antibodies to Histoplasma(35.9 EU,range 10.0-80.0 EU).Intravenous amphotericin was administered then transitioned to oral itraconazole.Follow-up computed tomography imaging showed a left lower lung nodule and mesenteric lymphadenopathy consistent with disseminated histoplasmosis infection.CONCLUSION Gastrointestinal involvement with H.capsulatum with no accompanying respiratory symptoms is exceedingly rare and recognition is often delayed due to the overlapping clinical manifestations of IBD.This case illustrates the importance of excluding infectious etiologies in patients with“biopsy-proven”CD prior to initiating immunosuppressive therapies.Communication between clinicians and pathologists is crucial as blood cultures and antigen testing are key studies that should be performed in all suspected cases of histoplasmosis to avoid misdiagnosis and inappropriate treatment.

Histoplasmosis and inflammatory bowel disease: A case report

BACKGROUND Infection with Histoplasma capsulatum can lead to a disseminated disease involving the gastrointestinal tract presenting as diffuse abdominal pain and inflammatory diarrhea which may mimic inflammatory bowel disease(IBD).CASE SUMMARY In the current report,we discuss the case of a 41-year old male who presented to the emergency department with complaints of high-grade intermittent fevers and severe abdominal pain with associated diarrhea and hematochezia.Laboratory results demonstrated transaminitis and elevated erythrocyte sedimentation rate,C-reactive protein and ferritin levels.The patient’s presentation was thought to be an exacerbation of his underlying IBD,but further investigations revealed a positive Histoplasma antigen in the urine.The patient was offered a colonoscopy and biopsy to confirm the diagnosis;however,he refused.He was treated with itraconazole and showed significant improvement of his symptoms,thereby confirming the diagnosis of gastrointestinal histoplasmosis.CONCLUSION Here within,we provide a review of IBD,evaluation of chronic diarrhea,and gastrointestinal histoplasmosis.

Disseminated histoplasmosis in primary Sjogren syndrome:A case report

BACKGROUND Sj?gren syndrome(SS)is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands.And histoplasmosis is an invasive mycosis caused by the saprophytic dimorphic fungus H.capsulatum.In patients with primary SS(PSS),disseminated histoplasmosis(DH)is extremely rare.CASE SUMMARY We report a 37-year-old female patient admitted to our hospital with exacerbating fatigue,somnolence,and pancytopenia as the main symptoms.She was eventually diagnosed with DH based on pancytopenia,splenomegaly,and findings of bone marrow smears.The atypical clinical symptoms made the diagnosis process more tortuous.Unfortunately,she died of respiratory failure on the day the diagnosis was confirmed.CONCLUSION We present a rare and interesting case of DH in a PSS patient.This case updates the geographic distribution of histoplasmosis in China,and expands the clinical manifestations of DH in PSS,highlighting the significance of constantly improving the understanding of PSS with DH.

Peritoneal Histoplasmosis about a Case and Literature Review

Histoplasmosis is an opportunistic granulomatous fungal infection. Peritoneal histoplasmosis (PH) is a rare form. The first case of PH was described in 1970 but this is the first case reported in Mauritania. We report the case of a 60-year-old male patient with a history of pulmonary tuberculosis, treated and declared cured, and partial epileptic seizures treated with Carbamazepine. Contrast computed tomography of the abdomen showed a large mass with a large intraperitoneal fluid component with a finely calcified wall in places, for which laparoscopy and biopsy were performed, identifying Histoplasma capsulatum infection. The subject received treatment with amphotericin B deoxycholate with good evolution, and outpatient management with itraconazole. PH is a rare entity that requires high clinical suspicion, especially in immunocompetent patients. The patient was informed that non-identifying information from the case would be submitted for publication, and he provided consent.

Primary Histoplasmosis of Larynx: A Case Series and Review of Literature

Objective: Aim of the study was to analyze 10 managed cases of Primary Histoplasmosis of Larynx, over a period of 10 years. Design: Retrospective, non-randomized, interventional case series. Patients and Method: This study was conducted in the Department of Otorhinolaryngology S.M.S Medical College from 2002 to 2011. The study consisted of evaluation of self-reported and referred patients who presented to ENT OPD and emergency. In all the cases a detailed history and clinical examination was done. All the patients underwent fiber optic laryngoscopy and subsequent direct laryngoscopy and biopsy. CT Scans were obtained for few cases. The study was a retrospective analysis of 10 treated cases. Main Outcome and Measures: Success of the treatment was defined as resolution of symptoms, differ-entiation from malignancy, no recurrence and regular follow up. Result: A total of 10 cases were managed between 2002 and 2011 and were reviewed. The main presentation was hoarseness of voice, with lesion simulating malignancy. Most common site of involvement was false cord and aryepiglottic fold (6 cases). Primary laryngeal Histoplasmosis was essentially a disease of adult males in all 10 cases. Treatment was exclusively medical with use of Itraconazole as drug of choice in 7 cases. Conclusion: Isolated laryngeal Histoplasmosis is a rare entity. Because of its simulation with malignancy it needs to be included in the differential diagnosis of neoplasm both benign and malignant. Our study clearly limits this kind of disease to adult males most commonly involving false cord and aryepiglottic fold in an endophytic pattern. Though it looks like cancer;biopsy confirms the diagnosis. The treatment is mainly medical with Itraconazole being the drug of choice.

Differential Diagnosis Value of lSF-FDG Imaging in Lung Histoplasmosis and Lung Cancer

In order to confirm the accuracy of ECT （emission computed tomography） scanning imaging in the diagnosis of lung histoplasmosis is higher than CT （computed tomography） scan. We retrospect a lung histoplasmosis patient, he was examined by the CT scan and ECT scanning, respectively. Results showed that lung cancer for CT diagnosis and large benign lesions for 18F-FDG （18F-fluorodeoxyglucose） ECT diagnosis. This indicated that the ECT diagnosis for benign lesions in the lung maybe have higher accuracy than CT scan.

Hepatic Histoplasmosis: An Update

Histoplasma capsulatum is the most common cause of en-demic mycosis in developing countries. It is a self-limited and asymptomatic disease in immunocompetent individu-als but remains a frequent cause of opportunistic infection in patients with compromised immune status. Liver in-volvement as a part of disseminated histoplasmosis is well known. However, liver infection as a primary manifestation of histoplasmosis without evidence of primary lung involve-ment is rare. In conclusion, clinicians should be aware of isolated histoplasmosis affecting the hepatobiliary system, and careful evaluation is warranted to confirm the diagno-sis. Given the appropriate clinical context, histoplasmosis should be considered in both immunocompetent and immu-nocompromised patients, regardless of pulmonary symp-toms, in non endemic as well as endemic areas.

Giemsa and Grocott in the recognition of Histoplasma capsulatum in blood smears

Objective:To facilitate the recognition of intracellular yeasts of Histoplasma capsulation and differentiate it from Leishmania amastigotes and other parasites,using the combination of Giemsa and a rapid modification of Grocott stains to peripheral blood smears in a hematological study.Methods:The combination of both stains was applied consecutively(first Grocott and then Giemsa)to previously fixed peripheral blood smears.Microscopy was performed with 400x and 1000x,the latter using immersion oil.Results:The yeasts of Histoplasma capsulatum were observed into the cytoplasm of leukocytes as brownish oval elements,with 3-4μm in diameter.Conclusions:The combination of both techniques is a simple and fast method to facilitate recognition of intracellular yeasts and it is different from intracellular parasitic elements.Moreover,it allows distinguishing the cell elements that are in the microscopic preparations.It may be very helpful in those cases in which the presumptive diagnosis of histoplasmosis has not been established yet and where other more sophisticated methods are not available.

Non habitual microscopic forms of Histoplasma capsulatum in disseminated disease

This paper communicates the presence of aberrant microscopic forms of Histoplasma capsulatum in a sample obtained by scrapping of the skin lesion and stained with a rapid modification of the Grocott technique.The AIDS patient was treated with cream contained corticoids and antifungal and antibacterial antibiotics by an erroneous diagnosis.Once the etiologic diagnosis was achieved,oral itraconazol was administrated at the daily dose of 400 mg during at least six months.These non habitual forms described in the literature as " aberrant variants", can be interpreted as an "adaptive phenomenon" of this termodimorphic fungal specie,as response of the ecologic alterations produced by antibiotic on the local antagonic bacterial microbiota,the deleterous activity of antifungal on the fungal cells and the local inmunodepression produced by the corticoids.

Invasive Infections for Endemic Fungi in Pediatrics in Guatemala

Background: Invasive fungal infections are common opportunistic diseases in patients with AIDS, other conditions related to immunodeficiency and healthy infants. Most publications on this subject are related to industrialized countries, and in adult population, with limited data in Latin America (except for Brazil, Colombia, and Argentina), and especially in pediatric population. These patients present a variety of clinical manifestations representing a diagnostic and therapeutic challenge for the health system. Objective: The objective of the study is to describe the epidemiological and laboratory characteristics of children with invasive fungal infections in Guatemala. Methods: A review of the microbiology service database was carried out at Roosevelt Hospital in Guatemala. Positive cultures were taken from children under 15 years of age, in a period of seven years, from 2007 to 2014, with its corresponding medical history. Results: Finally, 23 isolates were documented but only 15 patients were included in the study with complete information;10 Histoplasma capsulatum cases, 4 Cryptococcus neoformans cases and 1 Coccidioidessp case. The average age was 7 years old for Histoplasma and 9 years old for Criptococo, with an age range from 6 months to 14 years. Around 60% of the patients were older than 5 years, of which, more than two-thirds were HIV positive children without antiretroviral therapy, who presented an invasive fungal infection at the time of HIV diagnosis. These infections are endemic in Guatemala, so the distribution was mostly uniform. Around 80% of the patients had some disease related to immunodeficiency and 70% were infected with human immunodeficiency virus (HIV). The microbiological isolation was from blood, bone marrow, lymph nodes, cerebrospinal fluid and urine. The predominant laboratory findings were decrease in hematological series. The most frequent clinical syndromes were fever, adenomegaly, hepatosplenomegaly, respiratory, gastrointestinal, neurological and weight loss. Mortality rate was 53% (from them, 62% were HIV positive). From these patients, an87% did not receive antifungal treatment in time due to late diagnosis of the infection. Conclusions: These infections should be considered when treating pediatric patients from tropical regions, with nonspecific systemic symptoms and signs, lymph node involvement and hematological alterations related to the mononuclear phagocytic system, mainly if they are patients infected by HIV in an advanced stage, infants, or children with a disease that weakens the immune system. When there is a high suspicion of a fungal infection, screening for HIV is mandatory;cultures should be taken early and together with rapid diagnostic tests. An antifungal treatment should be started immediately and then modified accordingly to laboratory results.

Colonic Bleeding Due to Histoplasma and Mycobacterium Coinfection in Renal Transplant Patient

Introduction： Histoplasmosis is a rare infectious condition caused by the fungus Histoplasma capsulatum that can be presented from asymptomatic to severe forms. Tuberculosis, still an endemic infection in some developing countries, can also have variable clinical presentations. Both diseases involve the lungs mostly, but in immunocompromised patients, especially those with advanced HIV infection and transplant patients, disseminated forms are more frequently found. Gastrointestinal involvement is unusual, and digestive bleeding is an even rarer complication. Case presentation： We report the case of a 39-year-old female who was diagnosed with a Mycobacterium tuberculosis and Histoplasma capsulatum coinfection occurring 11 years after a living-donor-related renal transplant. The patient presented a severe gastrointestinal bleeding caused by an ulcer in the ascending colon. She improved after a combined treatment with tuberculostatic and fungicidal drugs. Conclusions： Simultaneous gastrointestinal involvement by histoplasmosis and tuberculosis, presenting as severe digestive bleeding, with minimal respiratory symptoms associated, make this an extremely rare case and a diagnostic challenge. Therefore, it is important to keep a high clinical suspicion of opportunistic infection, especially in immunocompromised patient who presents with LGB.