Aspergillosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Haytham Allaham, M.D. [2]; Serge Korjian M.D.

Overview

Aspergillosis must be differentiated from other diseases that cause fever, chest pain, dyspnea, sinusitis, allergic symptoms, and elevated IgE concentrations. Differential diagnosis includes other infections (fungi, bacteria, viruses, and parasites), non-infectious pulmonary diseases (such as asthma, COPD, interstitial lung disease, bronchiectasis, and lung tumors), cardiac diseases (such as pericarditis, endocarditis, or myocarditis), facial diseases (such as infectious sinusitis, sinus tumor, or nasal polyps), systemic diseases (such as Hyper IgE syndrome, Churg-Strauss syndrome, granulomatosis with polyangiitis, Goodpasture's syndrome), congenital diseases (such as cystic fibrosis or ciliary dyskinesia), transplant-related complications (such as GVHD), diseases with cutaneous manifestations (such as eczema, scabies, deep vein thrombosis, cellulitis), and adverse drug reactions.

Diffential Diagnosis

Aspergillosis must be differentiated from other diseases that cause fever, chest pain, dyspnea, sinusitis, allergic symptoms, and elevated IgE concentrations. Differential diagnosis includes:

Pathogen Disease Geographic distribution High risk Groups Differentiating features Microscopic findings
Physical exam Laboratory findings
Fungal Histoplasmosis Mississippi and Ohio River valleys
  • Cave dwellers
  • Soil that contains bird or bat dropping[1]
  • Urine antigen testing
Yeast are typically smaller, with narrow-based budding, found intracellularly within macrophages
Coccidioidomycosis Southwestern US region Opportunistic infection seen in AIDS Serologic tests( enzyme immune assay )more sensitive Characteristic spherule appearance
Paracoccidioidomycosis[3] Central and South america Opportunistic infection seen in AIDS
  • Elevated liver enzymes
Smaller fungi with thin cell walls, forming mariner wheel appearance, circumferentially surrounding the parent cell.( Captain wheel appearance )
Sporotrichosis Ubiquitous Gardeners [4] + Sporotrichin skin test Finger or cigar shaped yeast.
Aspergillosis[5] Ubiquitous Cell wall detection using galactomannan antigen detection, Beta-D-glucan detection test. Septated hyphae with acute angle branching
Bacterial Anthrax Ubiquitous Live stock handlers NonmotileGram-positiveaerobic or facultatively anaerobicendospore-forming, rod-shaped bacterium
Legionella Ubiquitous Chronic lung disease

Building water systems

  • + Urine Antigen
Gram negative bacterium
Tuberculosis Asia,Africa Ill contact individuals Aerobicnon-encapsulatednon-motileacid-fast bacillus
Listeriosis Ubiquitous Pregnant women [8]

Adults > 65

Immunocompromised.

flagellatedcatalase-positive, facultative intracellularanaerobicnonsporulatingGram-positive bacillus
Brucellosis

Mexico, South and Central America

People who take unpasteurized dairy products Gram-negative bacteria,non-motile, encapsulated coccobacilli.
Scrub typhus Asia-Pacific region

Australia

Afghanistan

Hikers[9]
  • Indirect immunofluorescence
Gram-negative α-proteobacterium  intracellular parasite
Leptospirosis Temperate, tropical climates. People who work with animals
  • Antibodies labelled with fluorescent markers positive for leptospires.
Spiral-shaped bacteria with hooked ends on dark-field.
Cat scratch fever Ubiquitous cat licking a person's open wound, or bites or scratches a person[11]
  • enzymatic immunoassay positive for antibody to B henselae
  • lymphocytosis
Gram-negative bacteria. facultative intracellular parasites
Viral Chickenpox
  • Spots appearing in two or three waves
Whole infected cell (wc) ELISA for IgG.
Coxsackie A virus Children attending day care[13] Painful blisters in the mouth, palms and on the feet.

Rash, appears after episode of high fever.

Clinically diagnosed
Others Primary lung cancer Age >65 CT guided bronchoscopy + for malignant cells

Differentiating Aspergillosis in immunocompromised host

Aspergillosis is more common among immunocompromised patients who are at high risk for other fungal, bacterial, and viral infections. It should be differentiated from the following diseases:

Disease Differentiating signs and symptoms Differentiating tests
CNS lymphoma[14]
Disseminated tuberculosis[15]
Aspergillosis[16]
Cryptococcosis
Chagas disease[17]
CMV infection[18]
HSV infection[19]
Varicella Zoster infection[20]
Brain abscess[21][22]
Progressive multifocal leukoencephalopathy[23]
  • Symptoms are often more insidious in onset and progress over months. Symptoms include progressive weakness, poor coordination, with gradual slowing of mental function. Only seen in the immunosuppressed. Rarely associated with fever or other systemic symptoms

Differentiating invasive aspergillosis from other diseases

Invasive aspergillosis must be differentiated from other conditions with similar presentation. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality[24] for example, mucormycosis. The differentials include:

Disease General features Signs and Symptoms Radiological abnormalities Histopathological abnormalities Other differentiating characters
Facial/Sinus swelling and ulceration Cranial neuropathy Disturbance in ocular motility
Mucormycosis
  • +

(Mucosal thickening on the paranasal sinuses is more common in rhinocerebral mucormycosis(ROCM) than bacterial orbital cellulitis(BOC)[25]

  • +

(Specially if there is invasion of the cavernous sinus)

  • +

(Limited eye movement is more common in patients with rhino-cerebral mucormycosis (ROCM) than in those with bacterial orbital cellulitis)[26]

  • Nonpigmented, wide (5- to 20-μm), thin-walled, ribbon-like hyphae with few septations (pauciseptate) and right-angle branching[27]
  • In lesions exposed to air, thick-walled spherical structures can form at the ends of the hyphae
  • Fungal elements invading the blood vessel wall or inside their lumen
Invasive aspergillosis
  • +
  • +
  • +

(There may be painful ophthalmoplegia if there is invasion of the cavernous sinus)[30]

Orbital cellulitis
  • +
  • +

(The ocular symptoms of bacterial orbital cellulitis (BOC) , such as facial edema, pain, and blepharoptosis, are similar to those of rhino-cerebral mucormycosis (ROCM) soon after infection onset, therefore it maybe difficult to distinguish the two during the initial phase of infection.

Eye lid swelling is more common in BOC than ROCM)[33]

Extra nodal T cell lymphoma
  • +

(Primary CNS NK/Tcell lymphoma of the nasal type)

  • +/-
Cutaneous Anthrax
  • +

References

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