01Approach to the Critical Patient/attcp33

Immediate priorities

›Critical stabilization triggers

›Septic shock physiology

›SBP < 90 mmHg or MAP < 65 mmHg

›Lactate >= 2 mmol/l

›CNS involvement

›Altered mental status or GCS < 13

›Meningeal signs: neck stiffness, photophobia, Kernig/Brudzinski

›Respiratory failure

›SpO2 < 90% on room air

›Signs of cavitary pulmonary sporotrichosis

›Initiate IV antifungal therapy immediately when disseminated disease confirmed

›Liposomal amphotericin B (L-AmB) 3-5 mg/kg/day IV

›Do not delay for culture confirmation when clinical picture is compelling

Monitoring and targets

›Monitoring bundle

›Continuous pulse oximetry

›SpO2 target >= 94%

›Renal function monitoring

›Creatinine and electrolytes daily during amphotericin B therapy

›Nephrotoxicity risk is lower with liposomal vs deoxycholate formulation

›Itraconazole trough levels

›Target trough > 0.5 mcg/mL

›Check at 2 weeks after initiation then periodically

Consult triggers

›Mandatory infectious disease consultation

›All cases of disseminated sporotrichosis

›HIV co-infection management and ART optimization

02History/hx58

Presentation pattern

›Core syndrome

›Subacute-to-chronic onset of multifocal skin lesions

›Non-contiguous distribution distinguishing from lymphocutaneous form

›Nodules, ulcers, or plaques in non-dermatomal distribution

›Constitutional symptoms

›Fever (significantly associated with systemic disease, p = .001)

›Weight loss (p = .006)

›Malaise and fatigue

›Organ-specific symptoms by system

›Pulmonary: cough, hemoptysis, dyspnea, pleuritic chest pain

›MSK: joint pain, swelling, bone pain, decreased range of motion

›Neuro: headache, confusion, behavioral changes, visual hallucinations

›Ocular: vision changes, eye pain, photophobia

›Mucosal: oral or nasal ulcers

Exposure history

›Zoonotic and environmental exposures

›Cat contact

›Sick or stray cats with skin lesions (major vector in endemic areas, Brazil)

›Scratches or bites from infected cats

›Environmental exposures

›Soil, sphagnum moss, rose bushes, hay, organic debris

›Floriculture, agriculture, mining occupations

›Geographic residence or travel

›Tropical and subtropical regions

›Latin America (especially Brazil), southeastern US, East Asia

›Endemic area exposure associated with aPR 1.64 for systemic infection

03Physical Exam/exam55

Vitals and general

›Stability assessment

›Temperature

›Fever may be low-grade or high

›Hemodynamic instability in severe cases

›Heart rate and blood pressure

›Tachycardia with sepsis physiology

›Hypotension in severe disseminated disease

›Mental status

›GCS and orientation assessment

›Behavioral changes suggesting CNS involvement

Skin and lymph node exam

›Cutaneous findings

›Multiple erythematous nodules, papules, plaques, or ulcers

›Non-contiguous and non-lymphatic distribution

›Hallmark of hematogenous dissemination

›Lesion characteristics

›Verrucous or hyperkeratotic plaques

›Ulcerated lesions with granulomatous base

›Fixed cutaneous lesions not following lymphatic spread

›Mucosal involvement

›Oral or nasal ulcers

›Conjunctival lesions

›Lymphadenopathy

›Regional lymphadenopathy

›Generalized lymphadenopathy in severe dissemination

Organ-system examination

›Pulmonary exam

04Differential Diagnosis/ddx40

Life-threatening mimics

›Other disseminated endemic mycoses

›Histoplasmosis (disseminated)

›ICD-10 B39.3

›Urine and serum Histoplasma antigen; endemic overlap in Americas

›Cryptococcosis (disseminated)

›ICD-10 B45.9

›Serum and CSF CrAg; mucicarmine stain on histopathology

›Talaromycosis (Talaromyces marneffei)

›Southeast Asia endemic; umbilicated papules in HIV patients

›Paracoccidioidomycosis

›Latin America; "pilot wheel" yeast morphology

›Blastomycosis

›Verrucous skin lesions plus pulmonary disease; broad-based budding yeast

Cutaneous and noduloulcerative mimics

›Infectious mimics

›Cutaneous leishmaniasis

›ICD-10 B55.1

›Travel history; biopsy with amastigotes

›Nocardiosis

›Lymphocutaneous spread pattern; partially acid-fast organisms

›Atypical mycobacterial infection

›M. marinum and M. kansasii; aquatic or soil exposure

›AFB stain and culture

›Disseminated tuberculosis

›PPD or IGRA; AFB cultures

›Non-infectious mimics

›Pyoderma gangrenosum

05Laboratory Tests/lt49

Microbiological diagnosis

›Fungal culture (gold standard)

›Tissue or skin biopsy culture

›Sabouraud dextrose agar at 25-30 degrees Celsius

›Sporothrix spp. grows as mold at room temperature; yeast at 37 degrees

›Blood cultures for disseminated disease

›Fungemia may be detected in severe dissemination

›Lysis-centrifugation technique increases yield

›CSF culture for CNS disease

›Lumbar puncture mandatory when neurological symptoms present

›Synovial fluid culture for osteoarticular involvement

›Histopathology

›PAS and GMS stains for yeast identification

›Cigar-shaped yeasts (2-6 microns) characteristic

›Asteroid bodies (Splendore-Hoeppli phenomenon)

›Autofluorescence on H&E sections

›Aids identification when yeasts sparse

›Suppurative and granulomatous inflammation pattern

Serological and molecular testing

›Sporothrix serology

›Sporothrix antibody detection (ELISA or immunodiffusion)

›Useful in resource-limited settings

›Sensitivity varies by assay and disease form

›No FDA-approved antigen detection assay available

›Molecular testing

›PCR for Sporothrix DNA from tissue

›Not widely standardized or commercially available

›Species identification (S. brasiliensis vs S. schenckii vs S. globosa)

06Diagnostic Tests/dt51

Scoring Systems

›Severity assessment tools

›No validated sporotrichosis-specific severity score exists

›Risk stratification based on organ involvement and immune status

›CNS involvement denotes highest mortality category

›Organ system involvement classification

›Cutaneous disseminated: skin lesions in non-contiguous distribution

›Pulmonary: cavitary or diffuse pulmonary infiltrates

›Osteoarticular: >= 2 bone or joint sites affected

›CNS: meningitis, leptomeningitis, encephalitis

›Ocular: endophthalmitis, chorioretinitis

›Multisystem: >= 2 organ systems beyond skin

›Host immune status classification

›HIV/AIDS with CD4 < 200 cells/mm3: highest risk for dissemination

›Transplant recipient: intermediate to high risk

›Immunocompetent host with dissemination: rare, warrants immune workup

MRI

›CNS sporotrichosis MRI

›Brain MRI with gadolinium for suspected CNS involvement

›Leptomeningeal enhancement pattern

›Communicating hydrocephalus from meningeal inflammation

›Periventricular signal changes

›Spine MRI for paraplegia or focal neurological deficits

›Epidural abscess or cord compression evaluation

›Spinal cord signal changes

›MRI brain preferred over CT for posterior fossa and meningeal detail

›Higher sensitivity for early leptomeningitis

›Gadolinium essential for meningeal disease

07Disposition/dispo39

Admission criteria

›Mandatory inpatient admission indications

›All confirmed or suspected disseminated sporotrichosis

›IV antifungal induction therapy required

›Close monitoring for drug toxicity

›CNS involvement

›ICU-level care for meningitis with altered mental status

›Neurosurgical consultation for hydrocephalus

›Septic shock or hemodynamic instability

›ICU admission with vasopressor support

›Severe pulmonary disease

›Respiratory failure requiring supplemental oxygen or ventilation

›Inability to tolerate oral medications

›Nausea, vomiting, or GI dysfunction

Level of care

›ICU indications

›Hemodynamic instability or septic shock

›CNS disease with GCS < 13

›Respiratory failure requiring ventilatory support

›Multiorgan dysfunction

›Infectious disease consultation

›Mandatory for all disseminated cases

›Species identification and antifungal susceptibility guidance

›Subspecialty consultations based on organ involvement

›Neurology or neurosurgery for CNS disease

›Orthopedics for osteoarticular disease requiring intervention

›Pulmonology for severe or cavitary pulmonary disease

›Ophthalmology for ocular sporotrichosis

08Treatment/t61

Induction antifungal therapy

›Liposomal amphotericin B (first-line for disseminated disease)

›Dose

›3-5 mg/kg/day IV

›Preferred over amphotericin B deoxycholate for reduced nephrotoxicity

›Duration of induction

›Continue until clinical stabilization and step-down possible

›Minimum 2 weeks typically before transition to itraconazole

›CNS disease requires longer induction (4-6 weeks)

›Monitoring

›Renal function and electrolytes daily

›Potassium replacement to maintain > 3.5 mmol/l

›Magnesium replacement as needed

›Pre-medication with acetaminophen and diphenhydramine for infusion reactions

›Amphotericin B deoxycholate (alternative if liposomal unavailable)

›Dose

›0.7-1.0 mg/kg/day IV

›Higher nephrotoxicity risk

›Hydration with 500-1000 mL normal saline before infusion

›Monitor creatinine every 2-3 days

Step-down and maintenance therapy

›Itraconazole (oral step-down and maintenance)

›Dose

›200 mg PO twice daily

›Capsule formulation taken with acidic beverage and fatty meal for absorption

›Solution formulation taken on empty stomach

›Duration

›Minimum 12 months after clinical response

09Special Populations/sp43

Pregnancy

›Pregnancy considerations

›Antifungal safety

›Amphotericin B is the preferred agent in pregnancy

›Liposomal amphotericin B preferred for reduced maternal nephrotoxicity

›Itraconazole is teratogenic (FDA category D) and contraindicated in first trimester

›Clinical course in pregnancy

›Disseminated sporotrichosis in pregnancy is rare but life-threatening

›Immunological changes of pregnancy may alter susceptibility

›Delivery considerations

›Infectious disease and maternal-fetal medicine co-management

›Neonatal monitoring if maternal disseminated disease

›Treatment duration

›Amphotericin B maintained throughout pregnancy if disseminated

›Switch to itraconazole postpartum after breastfeeding cessation

Geriatric

›Older adult considerations

›Altered pharmacokinetics

›Reduced renal clearance increases amphotericin B nephrotoxicity risk

›More aggressive electrolyte monitoring required

›Itraconazole absorption may be reduced with achlorhydria

›Atypical presentation

›Fewer systemic symptoms despite severe dissemination

›Cognitive changes may mimic dementia rather than CNS sporotrichosis

›Comorbidity burden

›Diabetes and malignancy more prevalent in older patients

›Drug-drug interactions with polypharmacy more likely

›Functional decline

10Background/b64

Epidemiology

›Global epidemiology

›Causative organisms

›Sporothrix schenckii (global distribution)

›Sporothrix brasiliensis (hyperendemic in Brazil; higher virulence)

›Sporothrix globosa (East Asia)

›Overall sporotrichosis incidence

›Neglected tropical disease with rising incidence

›One-year mortality 17% overall for all sporotrichosis forms

›Mortality rises to 37% in HIV co-infected patients with dissemination

›Distribution

›Tropical and subtropical regions globally

›Brazil: largest hyperendemic zone with zoonotic cat-to-human epidemic

›Latin America, southeastern United States, Japan, South Africa

›At-risk populations

›Malignancy present in 25% of global cohort

›HIV co-infection strongest single risk factor

›Hyperferritinemia associated with higher mortality in disseminated cases

Pathophysiology

›Infection mechanisms

›Transmission routes

›Traumatic inoculation: most common route (thorns, splinters, cat scratches)

›Zoonotic transmission: cat bites and scratches (S. brasiliensis epidemic in Brazil)

›Inhalation: primary pulmonary sporotrichosis (rare, mimics tuberculosis)

›Dimorphic fungal biology

›Mold form at environmental temperatures (23-26 degrees Celsius)

›Yeast form at 37 degrees Celsius (pathogenic tissue form)

›Thermal conversion is key virulence requirement

11Patient Discharge Instructions/pdi28

copy discharge instructions

›Diagnosis and condition explanation

›You have been diagnosed with disseminated sporotrichosis

›A serious fungal infection caused by Sporothrix that has spread to multiple areas of the body

›This requires long-term antifungal treatment lasting at least 12 months

›Medications

›Take itraconazole exactly as prescribed

›Capsules: take with a full meal and an acidic beverage (cola or orange juice) to improve absorption

›Solution: take on an empty stomach

›Do not skip doses; premature discontinuation leads to relapse

›Avoid grapefruit juice while taking itraconazole

›Report any side effects including nausea, abdominal pain, leg swelling, or yellowing of skin

›Exposure precautions

›Avoid contact with cats especially stray or sick cats

›Wear gloves when gardening or handling soil and plant material

›Avoid contact with sphagnum moss, rose bushes, or hay without protective gloves

›Follow-up

›Infectious disease appointment within 1-2 weeks of discharge is mandatory

›Blood test for itraconazole level at 2 weeks after starting medication

›Kidney function and electrolytes to be rechecked after completing IV amphotericin B

›HIV patients: CD4 count and viral load every 3 months

›Return to emergency department immediately for

›New or rapidly worsening skin lesions

›Fever, chills, or night sweats

›Severe headache, neck stiffness, confusion, or vision changes (signs of CNS involvement)

›New joint pain or swelling

›Cough, coughing up blood, or worsening shortness of breath

›Nausea, vomiting, or inability to take oral medications

12References/r27

Guidelines and key sources

›ECMM Global Guideline for Endemic Mycoses

›Thompson GR, Le T, Chindamporn A, et al. Global Guideline for the Diagnosis and Management of the Endemic Mycoses. Lancet Infectious Diseases. 2021. PMID 34364529

›First-line recommendation: L-AmB 3-5 mg/kg/day with itraconazole step-down

›IDSA Opportunistic Infections Guidelines (HIV)

›Benson C, Brooks J, Dhanireddy S, et al. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. IDSA/OARAC 2025

›Secondary prophylaxis itraconazole 200 mg daily until CD4 > 200 cells/mm3

›Neglected Endemic Mycoses Review

›Queiroz-Telles F, Fahal AH, Falci DR, et al. Neglected Endemic Mycoses. Lancet Infectious Diseases. 2017. PMID 28774696

›Extracutaneous Sporotrichosis Review

›Ramirez-Soto MC. Extracutaneous Sporotrichosis. Clinical Microbiology Reviews. 2025. PMID 39807894

Epidemiology and clinical studies

›Global cohort outcomes

›Schapiro S, Pulciano N, Galindo-Ramirez J, et al. Epidemiology and Outcomes of Sporotrichosis: A Descriptive Real-World Analysis From a Global Cohort. Mycoses. 2026. PMID 41732997

›One-year mortality 17% overall; 37% in HIV co-infected

›HIV co-infection outcomes

›Uemura EVG, Rossato L. Sporotrichosis Co-Infection With HIV/AIDS. Mycoses. 2023. PMID 37376902

›69.5% of HIV co-infected develop systemic dissemination

›Clinical factors for systemic disease

›Magalhaes VCR, Colombo SA, Peres NTA, et al. Clinical Factors Associated With Systemic Sporotrichosis in Brazil. Mycoses. 2024. PMID 37743555

›Fever (p=.001), weight loss (p=.006), alcohol use (p=.009) associated with systemic disease

›Iatrogenic dissemination case

›White M, Adams L, Phan C, et al. Disseminated Sporotrichosis Following Iatrogenic Immunosuppression for Suspected Pyoderma Gangrenosum. Lancet Infectious Diseases. 2019. PMID 31473127

›Osteoarticular sporotrichosis

›Ramirez-Soto MC, Bonifaz A, Tirado-Sanchez A, et al. Differences in Epidemiological and Clinical Findings Between Localized and Systemic Osteoarticular Infection Caused by Sporothrix. Medical Mycology. 2025. PMID 40973070

›CNS sporotrichosis

›Taborda MH, Costa FB, Kleinubing JR, et al. Teaching NeuroImage: Leptomeningitis With Communicating Hydrocephalus in an Immunocompromised Patient With Disseminated Sporotrichosis. Neurology. 2024. PMID 38889379

›Antifungal susceptibility

Evidence & Review

Evidence & Review