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Disseminated Histoplasmosis
Histoplasmosis

Presentation

We report three cases with such atypical presentation. Our first patient presented with bowel perforation, the second with left-sided pleural effusion and the third with submandibular abscess. [ncbi.nlm.nih.gov]

Immune System

  • Splenomegaly

    This case highlights consideration of disseminated histoplasmosis in patients presenting with diffuse adenopathy along with hepatomegaly and/or splenomegaly in the right clinical setting. [ncbi.nlm.nih.gov]

    He fulfilled 5 of 8 diagnostic criteria: fever ≥38.5°C, splenomegaly, ≥2 cytopenias, ferritin level >500 ng/mL, and evidence of hemophagocytosis in the bone marrow. [bloodjournal.org]

    Many dogs have a protracted course of weight loss to emaciation, chronic cough, persistent diarrhea, fever, anemia, hepatomegaly, splenomegaly, lymphadenopathy, and nasopharyngeal and GI ulceration. [merckvetmanual.com]

  • Generalized Lymphadenopathy

    The majority of AIDS patients with disseminated disease have CD4 counts The most common clinical findings include fever, hepatomegaly, splenomegaly, and generalized lymphadenopathy. [hivinsite.ucsf.edu]

Entire Body System

  • Fever

    The patient's fever continued despite several days of treatment with meropenem, minocycline, and micafungin. [ncbi.nlm.nih.gov]

  • Weight Loss

    We present a case of a 64-year-old man with a prolonged history of fatigue, weight loss, fever, and kidney failure. Kidney biopsy showed severe granulomatous interstitial nephritis with numerous giant cells. [ncbi.nlm.nih.gov]

    Clinical signs may be nonspecific but often include respiratory difficulty, fever, depression, anorexia, and weight loss. [merckvetmanual.com]

  • Lymphadenopathy

    Histoplasmosis was acquired in South America; its manifestations included prolonged fever, splinter hemorrhages, erythema multiforme, arthritis, and mediastinal lymphadenopathy. [ncbi.nlm.nih.gov]

    Lymphadenopathy, hepatomegaly, ocular disease (conjunctivitis, granulomatous chorioretinitis, retinal detachment, optic neuritis), lameness, and cutaneous nodules or ulcers may also be seen. [merckvetmanual.com]

  • Anemia

    Here we report a case of progressive disseminated histoplasmosis with Comb's positive hemolytic anemia, which is infrequently reported from a country like India where histoplasmosis is not an endemic mycosis. [ncbi.nlm.nih.gov]

    Disseminated histoplasmosis is a systemic fungus disease characterized by weakness, weight loss, fever, hepatosplenomegaly, anemia, and frequently by leukopenia. [annals.org]

    Evaluation of his anemia revealed a ferritin level of 85 000 ng/mL, which was a level that prompted consideration of hemophagocytic lymphohistiocytosis (HLH) as a unifying diagnosis. [bloodjournal.org]

    Many dogs have a protracted course of weight loss to emaciation, chronic cough, persistent diarrhea, fever, anemia, hepatomegaly, splenomegaly, lymphadenopathy, and nasopharyngeal and GI ulceration. [merckvetmanual.com]

  • Chills

    Symptoms Chills Cough Fever Headache Joint pain Mental status changes Muscle aches and stiffness Nausea, vomiting Possible rash (erythema nodosum) Skin lesions Visual changes (chorioretinitis) Signs and tests A physical examination may show abnormalities [ufhealth.org]

    […] symptoms develop, onset occurs 3-14 days after exposure. [14] Acute is defined as less than 1 month of symptoms, whereas subacute refers to more than 1 month of symptoms but less than 3 months. [1] Fever, headache, malaise, myalgia, abdominal pain, and chills [emedicine.medscape.com]

    Presentation Features Acute pulmonary histoplasmosis (lung disease) Approximately 90% of patients have no symptoms If symptoms develop, they will start within 3-14 days after exposure Symptoms are similar to flu-like symptoms (chills, fever, headache, [dermnetnz.org]

    MARIO MADRUGA, MD, MARK WALLACE, MD, ANGELA WABULYA, MD, and NA’IM FANAIAN, MD Orlando Health, Orlando, Fla MARY HILAL, MS4 Florida State University For 3 days, a 28-year-old woman with a history of polymyositis and possible dermatomyositis had fever, chills [consultant360.com]

    The symptoms of pulmonary histoplasmosis are similar to those of pneumonia and include flu-like symptoms such as fever, chills, sweats, a dry cough, malaise, and chest pains. Some affected people also experience joint pains. [medicinenet.com]

Respiratoric

  • Cough

    The acute form may produce fever, worsening cough, weight loss, malaise, and dyspnea. Approximately 5-20% of patients have CNS involvement. [emedicine.medscape.com]

    Case report We report the case of a young Cameroonian woman who presented with cough, hyperthermia, weight loss, pancytopenia, and hepatosplenomegaly. A positive HIV serology was discovered and a chest radiography revealed a 'miliary pattern'. [ncbi.nlm.nih.gov]

    The acute respiratory disease is characterized by respiratory symptoms, a general ill feeling, fever, chest pains, and a dry or nonproductive cough. Distinct patterns may be seen on a chest X-ray. [diagnose-me.com]

    […] and other respiratory symptoms Skin lesions and joint pain occur in 5-6% of patients, mainly female Chronic pulmonary histoplasmosis Occurs mostly in patients with underlying lung disease Symptoms include coughing up blood, weight loss, malaise, fever [dermnetnz.org]

  • Painful Cough

    Patients infected with large amounts may have difficulty breathing, chest pain, cough and other respiratory symptoms Skin lesions and joint pain occur in 5-6% of patients, mainly female Chronic pulmonary histoplasmosis Occurs mostly in patients with [dermnetnz.org]

    chills, pleuritic chest pain, weight loss, malaise, myalgias, and sweats. [aafp.org]

    Symptoms of fever, chills, sweats, headache, myalgia, anorexia, cough, and chest pain characterize these illnesses ( 10 ), and respiratory failure and death may ensue ( 103 ). [antimicrobe.org]

  • Sneezing

    If an infected person coughs or sneezes on another person the microorganisms, suspended in warm, moist droplets, may enter the body through the nose, mouth or eye surfaces. [en.wikipedia.org]

Gastrointestinal

  • Diarrhea

    Chronic GI signs, especially large intestinal diarrhea, are usually most obvious in dogs, but cats tend to have respiratory and nonspecific clinical signs. [merckvetmanual.com]

    Aside from constitutional symptoms, gastrointestinal involvement may produce diarrhea and abdominal pain. [emedicine.medscape.com]

    Abstract Background A 56-year-old female with a 30-year history of ileocolic Crohn's disease presented with a 1-month history of bloody diarrhea and decreased caliber of stools; physical examination revealed a broad indurated anal fissure. [nature.com]

    Symptoms mainly showed as abdominal pain, diarrhea, anorexia, nausea, bilious vomiting, constipation, tenesmus and abdominal tenderness [ 6 ]. [omicsonline.org]

    Side effects of myelosuppression, diarrhea, and hepatotoxicity can be reversed with folic or folinic acid. [clinicaladvisor.com]

  • Abdominal Pain

    Featured: Abdominal Pain (Adults) Abdominal pain in adults can range from a mild stomach ache to severe pain. [emedicinehealth.com]

    Aside from constitutional symptoms, gastrointestinal involvement may produce diarrhea and abdominal pain. [emedicine.medscape.com]

    Symptoms mainly showed as abdominal pain, diarrhea, anorexia, nausea, bilious vomiting, constipation, tenesmus and abdominal tenderness [ 6 ]. [omicsonline.org]

    (b) Generalized erythematous maculopapular rash, observed on follow-up Click here to view Seven months later, she presented with high fever, severe cough with expectoration, abdominal pain, and distension with generalized erythematous maculopapular rash [e-ijd.org]

    The most common manifestations include diarrhea, vague abdominal pain, and fever. Intestinal obstruction and perforation have been reported. [hivinsite.ucsf.edu]

  • Abdominal Distension

    Six months later, she had abdominal distension and received prednisone, hydroxychloroquine and azathioprine. [ncbi.nlm.nih.gov]

    Blood 2014 123:2449; doi: https://doi.org/10.1182/blood-2014-01-550657 A 25-year-old Guatemalan man presented to the hospital with abdominal distension and fever. [bloodjournal.org]

    In September 2013, the following symptoms appeared: abdominal distension, fever, night sweating, and the development of a palpable mass on the neck. [kjim.org]

    A few days later he developed abdominal distension, was taken to another hospital for treatment and died there a couple of days later. [jpma.org.pk]

  • Gastropathy

    Patients with HIV infection may have decreased acid secretion, secondary to HIV gastropathy. Therapeutic concentrations with the capsule preparation may not be achieved in these patients. [hivinsite.ucsf.edu]

Jaw & Teeth

  • Oral Ulcers

    Oral ulcers are common in HIV-infected patients, with a broad differential, including viral, bacterial, fungal, mycobacterial and neoplastic aetiologies. [ncbi.nlm.nih.gov]

    Generally most of the cases of Histoplasmosis in India present with skin lesions and oral ulcers, mass lesions are uncommon presentation. [ijohsjournal.org]

Cardiovascular

  • Chest Pain

    Histoplasmosis Symptoms Chest Pain There are many causes of chest pain. A serious form of chest pain is angina, which is a symptom of heart disease and results from inadequate oxygen supply to the heart muscle. [medicinenet.com]

    The acute respiratory disease is characterized by respiratory symptoms, a general ill feeling, fever, chest pains, and a dry or nonproductive cough. Distinct patterns may be seen on a chest X-ray. [diagnose-me.com]

    Possible symptoms include: fever dry cough chest pain joint pain red bumps on your lower legs In severe cases, symptoms may include: excessive sweating shortness of breath coughing up blood Widespread histoplasmosis causes inflammation and irritation. [healthline.com]

    Acute symptomatic pulmonary histoplasmosis has a short duration, with possible symptoms including fever, chills, chest pain, and a non-productive cough. [encyclopedia.com]

  • Tachycardia

    Examination findings included resting tachycardia and melenic stool. Blood pressure was 95/50 mm Hg. Multiple raised, soft, bluish 0.3 to 1 cm lesions were noted on the trunk and extremities. [consultant360.com]

Liver, Gall & Pancreas

  • Hepatosplenomegaly

    Histoplasmosis is an uncommon cause of hepatosplenomegaly in South Africa. A case of immune reconstitution syndrome (IRS) to disseminated histoplasmosis in a patient presented to a tertiary hospital in Kwazulu-Natal, South Africa, is described. [ncbi.nlm.nih.gov]

  • Hepatomegaly

    A higher fever (≥38.5ºC), maculopapular/papular rash, splenomegaly, hepatomegaly, wheezing, hemoglobin ≤9.5g/dL, platelets ≤80,000/µL, CD4 count ≤75/µL, aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN), lactate dehydrogenase [ncbi.nlm.nih.gov]

    Lymphadenopathy, hepatomegaly, ocular disease (conjunctivitis, granulomatous chorioretinitis, retinal detachment, optic neuritis), lameness, and cutaneous nodules or ulcers may also be seen. [merckvetmanual.com]

    Subacute PDH usually presents with weight loss, fever and hepatomegaly in association with focal abnormalities such as lymphadenopathy, meningitis, oral or gastrointestinal ulceration, and adrenal insufficiency. [life-worldwide.org]

  • Jaundice

    On examination, he was found to be asthenic, normotensive, anaemic and jaundiced with hepatosplenomegaly. On investigation, his haemoglobin was found to be 9.5 gm/dl, ESR: 47 mm/h, total bilirubin: 2mg/di. [jpma.org.pk]

    There was clubbing of fingers but without lymphadenopathy, anemia, or jaundice. [atmph.org]

Musculoskeletal

  • Myalgia

    A 34-year-old, HIV-positive man living in Texas presented with a 2-week history of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face, and extremities, including the palms. Initially secondary syphilis was suspected. [ncbi.nlm.nih.gov]

    If symptoms develop, onset occurs 3-14 days after exposure. [14] Acute is defined as less than 1 month of symptoms, whereas subacute refers to more than 1 month of symptoms but less than 3 months. [1] Fever, headache, malaise, myalgia, abdominal pain, [emedicine.medscape.com]

    Acute primary histoplasmosis is a syndrome with fever, cough, myalgias, chest pain, and malaise of varying severity. Acute pneumonia (evident on physical examination and chest x-ray) sometimes develops. [merckmanuals.com]

    Symptoms vary from mild fever, myalgia, and cough, with increased sputum, to lassitude, pain in the chest, and shortness of breath. These usually start 8-15 days after exposure, and may be accompanied by arthralgia and erythema nodosum. [isradiology.org]

    A 13-year-old girl presented with malar rash [Figure 1] a, fever, myalgia, stiffness of hands and knees, and photosensitivity. [e-ijd.org]

Skin

  • Skin Lesion

    Disseminated skin lesions of acute life-threatening progressive disseminated histoplasmosis. Characteristic skin lesion of disseminated histoplasmosis in AIDS, showing central ulceration. [life-worldwide.org]

    Skin lesions and oral ulcers are seen in more than one-third of patients. Predisposing factors like exposure to birds, farming, mining, diabetes were observed in few patients. [ncbi.nlm.nih.gov]

    See also: Histoplasmosis Histoplasmosis - acute Histoplasmosis - chronic pulmonary Skin lesion of histoplasmosis Alternative Names Systemic histoplasmosis Causes, incidence, and risk factors Histoplasmosis is caused by a fungus found in the central and [ufhealth.org]

  • Sweating

    He had unintentional weight loss, low-grade fever, and night sweats. He has lived all his life in Lubbock, Texas. Physical examination was remarkable for left cerebellar signs, including dysmetria, dysdiadochokinesia, and positive Romberg’s sign. [neurology.org]

    Symptoms of chronic pulmonary histoplasmosis include: a severe cough that can produce green or yellow phlegm chest pain weight loss night sweats fatigue loss of lung parenchyma In most cases, symptoms last for several months and, if left untreated, can [diagnose-me.com]

    Possible symptoms include: fever dry cough chest pain joint pain red bumps on your lower legs In severe cases, symptoms may include: excessive sweating shortness of breath coughing up blood Widespread histoplasmosis causes inflammation and irritation. [healthline.com]

    His oral temperature was 40.6°C (105.1°F), and he had occasional rigors, emesis, and night sweats. [aafp.org]

    The symptoms of pulmonary histoplasmosis are similar to those of pneumonia and include flu-like symptoms such as fever, chills, sweats, a dry cough, malaise, and chest pains. Some affected people also experience joint pains. [medicinenet.com]

Neurologic

  • Confusion

    This case presentation underscores the broad spectrum of clinical presentations as well as the potential for diagnostic confusion with protozoa such as Leishmania or Trypanosoma species during histopathologic examination if special stains for fungal organisms [ncbi.nlm.nih.gov]

    CNS involvement may produce headache, visual and gait disturbances, confusion, seizures, altered consciousness, and neck stiffness or pain. The chronic form is associated with constitutional symptoms. [emedicine.medscape.com]

    Amphotericin B therapy is the treatment of choice for patients with AIDS who are admitted to the hospital with moderate to severe histoplasmosis.(5) In particular, a patient with presumptive or confirmed DH presenting with hypotension, hypoxemia, mental confusion [hivinsite.ucsf.edu]

  • Seizure

    CNS involvement may produce headache, visual and gait disturbances, confusion, seizures, altered consciousness, and neck stiffness or pain. The chronic form is associated with constitutional symptoms. [emedicine.medscape.com]

    Figure 6: MRI of the brain: An MRI of the brain was conducted when the patient developed an episode of generalized tonic–clonic seizures after 2 weeks of amphotericin B treatment. [atmph.org]

    If, however, a patient with Toxoplasma encephalitis has a history of seizures, then anticonvulsants should be administered at least through the acute treatment phase. [hivwebstudy.org]

  • Convulsions

    The patient developed generalized tonic–clonic convulsions and needed care for the critical condition 2 weeks into treatment. [atmph.org]

Workup

Investigations Laboratory workup done revealed red blood cell - 3.09 × 10 6 /Ul, hemoglobin - 8.7 g/dl, hematocrit - 24.4%, total leukocyte count - 3970/mm 3, normal differential count, and platelet count - 1,50,000/mm 3. [ijohsjournal.org]

An infectious disease team may be alerted when: The disease has not been definitively diagnosed after an initial workup The patient is immunocompromised (for example, in AIDS or after chemotherapy); The infectious agent is of an uncommon nature (e.g. [en.wikipedia.org]

Serum

  • Lymphopenia

    […] lymphocytes, and 3% monocytes), platelet count - 56,000/mm 3 ; C-reactive protein - 40 mg/L (normal [7] based on malar rash, photosensitivity, nonerosive arthritis, positive ANA, serositis (pleural effusion), and hematological disorder (leukopenia, lymphopenia [e-ijd.org]

Other Pathologies

  • Granulomatous Tissue

    tissue with multinucleated giant cells, epithelial histiocytes, and lymphocytic mononuclear inflammatory infiltrate. [atmph.org]

    Figure 1: Upper gastrointestinal endoscopy showing growth above epiglottis Click here to view The biopsy from oropharyngeal mass reveals an inflammatory granulomatous tissue composed of lymphocytes, plasma cells, neutrophils, and histiocytes. [ijohsjournal.org]

Treatment

This, we believe, is the first reported treatment of HLH with anakinra in a patient with AIDS and acute disseminated histoplasmosis. [ncbi.nlm.nih.gov]

Prognosis

Considering appropriate diagnosis and timely therapy, the reported patient had good prognosis despite being diagnosed with disseminated histoplasmosis. [ncbi.nlm.nih.gov]

What is the prognosis of histoplasmosis? People with mild symptoms of histoplasmosis usually resolve the disease on their own without treatment. In more severe cases, the prognosis is good for those who receive appropriate treatment. [medicinenet.com]

Etiology

HLH is a syndrome of pathologic immune activation characterized as primary or secondary in etiology. This patient had HLH secondary to disseminated histoplasmosis in the setting of severe immune deficiency. [bloodjournal.org]

Previous studies in endemic areas supported the hypothesis that new infection/reinfection, rather than reactivation, is the main etiology of symptomatic histoplasmosis. No previous reports have presented clinical evidence of reactivation. [ncbi.nlm.nih.gov]

2015/8/6/775/169927 Introduction Histoplasma capsulatum, a thermal dimorphic fungus, is the etiologic agent of histoplasmosis. It is most prevalent endemic mycosis in North America, whereas in India it is seen in the Gangetic delta. [mjdrdypu.org]

[…] pneumonia was found to be 10% to 15% among hospitalized patients with CAP and of them 6% developed progressive pneumonia. [5] Mortality of un-resolving pneumonia ranges from 27 to 49%. [6] Approximately, 20% of presumed non-responding CAP had noninfectious etiology [lungindia.com]

Histoplasma capsulatum (H. capsulatum), the etiologic organism for histoplasmosis, infects humans via the respiratory tract. After the organism reaches the alveolar space, it replicates in macrophages and spreads in the reticuloendothelial system. [clinicaladvisor.com]

Epidemiology

Published literature lacks systematic studies on disseminated histoplasmosis in India, and previous reviews on its epidemiology in India were conducted two decades back. [ncbi.nlm.nih.gov]

We need tests; we need treatments; but first of all, we physicians need to integrate our South American epidemiology in our diagnostic algorithms. [journals.plos.org]

Epidemiology and Pathology In the tropics, the fungi are found in both rural and urban areas, in soil around dead or hollow trees, in caves, and anywhere where there are bird or bat excreta. [isradiology.org]

Epidemiology and management of infectious complications in contemporary management of chronic leukemias. Infect Disord Drug Targets. 2011;11:3-10. https://doi.org/10.2174/187152611794407755 Kalkanis A, Judson MA, Napier MB. [revistabiomedica.org]

Pathophysiology

[…] profound, can calcify Extrapulmonary findings: Liver and spleen calcifications, adrenals, oral ulcers, bone marrow Differentials: Sarcoidosis and tuberculosis Usual treatment: Itraconazole; amphotericin for severe or diffuse disease Prognosis: Excellent Pathophysiology [emedicine.medscape.com]

Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology. Clin Infect Dis 1997; 24:1195-203. 10. Wheat J. Histoplasmosis in the acquired immunodeficiency syndrome. [hivinsite.ucsf.edu]

[clarification needed][21] Cause Pathogenic viruses Pathogenic bacteria Pathophysiology[edit] There is a general chain of events that applies to infections.[22] The chain of events involves several steps—which include the infectious agent, reservoir, [en.wikipedia.org]

The pathophysiology of disseminated Mycobacterium avium complex disease in AIDS. J Infect Dis. 1999;179 Suppl 3:S461-5. 59. Gordin FM, Cohn DL, Sullam PM, Schoenfelder JR, Wynne BA, Horsburgh CR Jr. [hivwebstudy.org]

Prevention

Ketoconazole has been used to prevent relapse, but available information suggests that up to 50 percent of AIDS patients relapse even with ketoconazole treatment. A more effective therapy to prevent recurrence is needed. [clinicaltrials.gov]

The National Institute for Occupational Safety and Health, along with the Center for Disease Control and Prevention (CDC), engages in promotions geared to educate employers and workers about the risks and prevention strategies for histoplasmosis. [encyclopedia.com]

Source: Centers for Disease Control and Prevention. Tables Table 1. [hivwebstudy.org]

A timely diagnosis, with appropriate therapies, could have prevented death. [ncbi.nlm.nih.gov]

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