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Aspergillosis differential diagnosis

Introduction

Overview

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

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,Β 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 Nonmotile,Β Gram-positive,Β aerobicΒ or facultativelyΒ anaerobic,Β endospore-forming,Β rod-shapedΒ bacterium
Legionella Ubiquitous Chronic lung disease

Building water systems

  • + Urine Antigen
Gram negativeΒ bacterium
Tuberculosis Asia,Africa Ill contact individuals Aerobic,Β non-encapsulated,Β non-motile,Β acid-fastΒ bacillus
Listeriosis Ubiquitous Pregnant women [8]

Adults > 65

Immunocompromised.

flagellated,Β catalase-positive, facultativeΒ intracellular,Β anaerobic,Β nonsporulating,Β Gram-positiveΒ 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
aΒ Gram-negativeΒ Ξ±-proteobacteriumΒ Β intracellular parasite
Leptospirosis Temperate, tropical climates. People who work with animals
  • Antibodies labelled with fluorescent markers positive for leptospires.
Spiral-shaped bacteriaΒ 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-negativeΒ bacteria. facultative intracellular parasites
Viral Chickenpox βˆ’
  • Spots appearing in two or three waves
Whole infected cell (wc)Β ELISAΒ for IgG. βˆ’
Coxsackie A virus βˆ’ Children attending day care[13] PainfulΒ blistersΒ in the mouth, palms and on the feet.

Rash, appears after episode of high fever.

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

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-ΞΌm), 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

References

  1. ↑ Information for Healthcare Professionals about Histoplasmosis. Centers for Disease Control and Prevention. 2015. Available at: http://www.cdc.gov/fungal/diseases/histoplasmosis/health-professionals.html. Accessed February 2, 2016.
  2. ↑ Brown J, Benedict K, Park BJ, Thompson GR (2013). “Coccidioidomycosis: epidemiology”. Clin Epidemiol. 5: 185–97. doi:10.2147/CLEP.S34434. PMCΒ 3702223. PMIDΒ 23843703.
  3. ↑ Marques SA (2013). “Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating”. An Bras Dermatol. 88 (5): 700–11. doi:10.1590/abd1806-4841.20132463. PMCΒ 3798345. PMIDΒ 24173174.
  4. ↑ Mahajan VK (2014). “Sporotrichosis: an overview and therapeutic options”. Dermatol Res Pract. 2014: 272376. doi:10.1155/2014/272376. PMCΒ 4295339. PMIDΒ 25614735.
  5. ↑ Sherif R, Segal BH (2010). “Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications”. Curr Opin Pulm Med. 16 (3): 242–50. doi:10.1097/MCP.0b013e328337d6de. PMCΒ 3326383. PMIDΒ 20375786.
  6. ↑ Hicks CW, Sweeney DA, Cui X, Li Y, Eichacker PQ (2012). “An overview of anthrax infection including the recently identified form of disease in injection drug users”. Intensive Care Med. 38 (7): 1092–104. doi:10.1007/s00134-012-2541-0. PMCΒ 3523299. PMIDΒ 22527064.
  7. ↑ Schuetz P, Haubitz S, Christ-Crain M, Albrich WC, Zimmerli W, Mueller B (2013). “Hyponatremia and anti-diuretic hormone in Legionnaires’ disease”. BMC Infect. Dis. 13: 585. doi:10.1186/1471-2334-13-585. PMCΒ 3880094. PMIDΒ 24330484.
  8. ↑ Lamont RF, Sobel J, Mazaki-Tovi S, Kusanovic JP, Vaisbuch E, Kim SK, Uldbjerg N, Romero R (2011). “Listeriosis in human pregnancy: a systematic review”. J Perinat Med. 39 (3): 227–36. doi:10.1515/JPM.2011.035. PMCΒ 3593057. PMIDΒ 21517700.
  9. ↑ Zhou YH, Xia FQ, Van Poucke S, Zheng MH (2016). “Successful Treatment of Scrub Typhus-Associated Hemophagocytic Lymphohistiocytosis With Chloramphenicol: Report of 3 Pediatric Cases and Literature Review”. Medicine (Baltimore). 95 (8): e2928. doi:10.1097/MD.0000000000002928. PMCΒ 4779037. PMIDΒ 26937940.
  10. ↑ Iroh Tam PY, Obaro SK, Storch G (2016). “Challenges in the Etiology and Diagnosis of Acute Febrile Illness in Children in Low- and Middle-Income Countries”. J Pediatric Infect Dis Soc. 5 (2): 190–205. doi:10.1093/jpids/piw016. PMIDΒ 27059657.
  11. ↑ Gouriet F, Lepidi H, Habib G, Collart F, Raoult D (2007). “From cat scratch disease to endocarditis, the possible natural history of Bartonella henselae infection”. BMC Infect. Dis. 7: 30. doi:10.1186/1471-2334-7-30. PMCΒ 1868026. PMIDΒ 17442105.
  12. ↑ De Paschale M, Clerici P (2016). “Microbiology laboratory and the management of mother-child varicella-zoster virus infection”. World J Virol. 5 (3): 97–124. doi:10.5501/wjv.v5.i3.97. PMCΒ 4981827. PMIDΒ 27563537.
  13. ↑ Flett K, Youngster I, Huang J, McAdam A, Sandora TJ, Rennick M, Smole S, Rogers SL, Nix WA, Oberste MS, Gellis S, Ahmed AA (2012). “Hand, foot, and mouth disease caused by coxsackievirus a6”. Emerging Infect. Dis. 18 (10): 1702–4. doi:10.3201/eid1810.120813. PMCΒ 3471644. PMIDΒ 23017893.
  14. ↑ Gerstner ER, Batchelor TT (2010). “Primary central nervous system lymphoma”. Arch. Neurol. 67 (3): 291–7. doi:10.1001/archneurol.2010.3. PMIDΒ 20212226.
  15. ↑ von Reyn CF, Kimambo S, Mtei L, Arbeit RD, Maro I, Bakari M, Matee M, Lahey T, Adams LV, Black W, Mackenzie T, Lyimo J, Tvaroha S, Waddell R, Kreiswirth B, Horsburgh CR, Pallangyo K (2011). “Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality”. Int. J. Tuberc. Lung Dis. 15 (8): 1087–92. doi:10.5588/ijtld.10.0517. PMIDΒ 21740673.
  16. ↑ LatgΓ© JP (1999). “Aspergillus fumigatus and aspergillosis”. Clin. Microbiol. Rev. 12 (2): 310–50. PMCΒ 88920. PMIDΒ 10194462.
  17. ↑ Rassi A, Rassi A, Marin-Neto JA (2010). “Chagas disease”. Lancet. 375 (9723): 1388–402. doi:10.1016/S0140-6736(10)60061-X. PMIDΒ 20399979.
  18. ↑ Emery VC (2001). “Investigation of CMV disease in immunocompromised patients”. J. Clin. Pathol. 54 (2): 84–8. PMCΒ 1731357. PMIDΒ 11215290.
  19. ↑ Bustamante CI, Wade JC (1991). “Herpes simplex virus infection in the immunocompromised cancer patient”. J. Clin. Oncol. 9 (10): 1903–15. doi:10.1200/JCO.1991.9.10.1903. PMIDΒ 1919640.
  20. ↑ Hambleton S (2005). “Chickenpox”. Curr. Opin. Infect. Dis. 18 (3): 235–40. PMIDΒ 15864101.
  21. ↑ Alvis Miranda H, Castellar-Leones SM, Elzain MA, Moscote-Salazar LR (2013). “Brain abscess: Current management”. J Neurosci Rural Pract. 4 (Suppl 1): S67–81. doi:10.4103/0976-3147.116472. PMCΒ 3808066. PMIDΒ 24174804.
  22. ↑ Patel K, Clifford DB (2014). “Bacterial brain abscess”. Neurohospitalist. 4 (4): 196–204. doi:10.1177/1941874414540684. PMCΒ 4212419. PMIDΒ 25360205.
  23. ↑ Tan CS, Koralnik IJ (2010). “Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis”. Lancet Neurol. 9 (4): 425–37. doi:10.1016/S1474-4422(10)70040-5. PMCΒ 2880524. PMIDΒ 20298966.
  24. ↑ Trief D, Gray ST, Jakobiec FA, Durand ML, Fay A, Freitag SK, Lee NG, Lefebvre DR, Holbrook E, Bleier B, Sadow P, Rashid A, Chhabra N, Yoon MK (2016). “Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus”. Br J Ophthalmol. 100 (2): 184–8. doi:10.1136/bjophthalmol-2015-306945. PMIDΒ 26112869.
  25. ↑ Son JH, Lim HB, Lee SH, Yang JW, Lee SB (2016). “Early Differential Diagnosis of Rhino-Orbito-Cerebral Mucormycosis and Bacterial Orbital Cellulitis: Based on Computed Tomography Findings”. PLoS ONE. 11 (8): e0160897. doi:10.1371/journal.pone.0160897. PMCΒ 4976984. PMIDΒ 27501044.
  26. ↑ Son JH, Lim HB, Lee SH, Yang JW, Lee SB (2016). “Early Differential Diagnosis of Rhino-Orbito-Cerebral Mucormycosis and Bacterial Orbital Cellulitis: Based on Computed Tomography Findings”. PLoS ONE. 11 (8): e0160897. doi:10.1371/journal.pone.0160897. PMCΒ 4976984. PMIDΒ 27501044.
  27. ↑ Guarner J, Brandt ME (2011). “Histopathologic diagnosis of fungal infections in the 21st century”. Clin. Microbiol. Rev. 24 (2): 247–80. doi:10.1128/CMR.00053-10. PMCΒ 3122495. PMIDΒ 21482725.
  28. ↑ Trief D, Gray ST, Jakobiec FA, Durand ML, Fay A, Freitag SK, Lee NG, Lefebvre DR, Holbrook E, Bleier B, Sadow P, Rashid A, Chhabra N, Yoon MK (2016). “Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus”. Br J Ophthalmol. 100 (2): 184–8. doi:10.1136/bjophthalmol-2015-306945. PMIDΒ 26112869.
  29. ↑ Hamilos G, Samonis G, Kontoyiannis DP (2011). “Pulmonary mucormycosis”. Semin Respir Crit Care Med. 32 (6): 693–702. doi:10.1055/s-0031-1295717. PMIDΒ 22167397.
  30. ↑ Siraj CA, Krishnan J, Nair RR, Girija AS (2005). “Invasive aspergillosis producing painful ophthalmoplegia”. J Assoc Physicians India. 53: 901–2. PMIDΒ 16459537.
  31. ↑ Jung J, Kim MY, Lee HJ, Park YS, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH (2015). “Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis”. Clin. Microbiol. Infect. 21 (7): 684.e11–8. doi:10.1016/j.cmi.2015.03.019. PMIDΒ 25882362.
  32. ↑ Chaudhry IA, Al-Rashed W, Arat YO (2012). “The hot orbit: orbital cellulitis”. Middle East Afr J Ophthalmol. 19 (1): 34–42. doi:10.4103/0974-9233.92114. PMCΒ 3277022. PMIDΒ 22346113.
  33. ↑ Son JH, Lim HB, Lee SH, Yang JW, Lee SB (2016). “Early Differential Diagnosis of Rhino-Orbito-Cerebral Mucormycosis and Bacterial Orbital Cellulitis: Based on Computed Tomography Findings”. PLoS ONE. 11 (8): e0160897. doi:10.1371/journal.pone.0160897. PMCΒ 4976984. PMIDΒ 27501044.
  34. ↑ Zhang Y, Wang T, Liu GL, Li J, Gao SQ, Wan L (2016). “Mucormycosis or extranodal natural killer/T cell lymphoma, similar symptoms but different diagnosis”. J Mycol Med. 26 (3): 277–82. doi:10.1016/j.mycmed.2016.04.005. PMIDΒ 27178138.
  35. ↑ Prajapati HJ, Vincentelli C, Hwang SN, Voloschin A, Crocker I, Dehkharghani S (2014). “Primary CNS natural killer/T-cell lymphoma of the nasal type presenting in a woman: case report and review of the literature”. J. Clin. Oncol. 32 (8): e26–9. doi:10.1200/JCO.2012.47.6796. PMIDΒ 24419127.
  36. ↑ Mallon E, McKee PH (1997). “Extraordinary case report: cutaneous anthrax”. Am J Dermatopathol. 19 (1): 79–82. PMIDΒ 9056659.
  37. ↑ Skiada A, Petrikkos G (2013). “Cutaneous mucormycosis”. Skinmed. 11 (3): 155–9, quiz 159–60. PMIDΒ 23930354.

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