Phaeohyphomycosis

Last updated
Phaeohyphomycosis
Specialty Infectious diseases [1]
Symptoms
Causes Breathing in or entry via a cut in the skin of dark filamentous fungi [3]
Diagnostic method Histology, culture, PCR [4]
Differential diagnosis Aspergillosis, chromoblastomycosis, cryptococcosis, mycetoma [3]
TreatmentSurgical debridement/drainage, antifungals [3]
Medication Itraconazole, amphotericin B [3]
FrequencyRare [5]

Phaeohyphomycosis is a diverse group of fungal infections, [6] caused by dematiaceous fungi whose morphologic characteristics in tissue include hyphae, yeast-like cells, or a combination of these. [7] It can be associated with an array of melanistic filamentous fungi including Alternaria species, [8] Exophiala jeanselmei , [9] and Rhinocladiella mackenziei . [10]

Contents

The term "phaeohyphomycosis" was introduced to determine infections caused by dematiaceous (pigmented) filamentous fungi which contain melanin in their cell walls. [11] Phaeohyphomycosis is an uncommon infection, but the number of cases reported has been increasing in recent years. Fungal melanin is thought to be a virulence factor. The outcome of antifungal treatment is poor, and mortality is almost 80%. [12] Phaeohyphomycosis has been attributed to more than 100 species and 60 genera of fungi over the past several decades. The pathogens are considered opportunistic. Almost all cases of widely disseminated infection have occurred in immunosuppressed people. [12]

Clinical signs of phaeohyphomycosis

Wildlife

Phaeohyphomycosis is found throughout the animal kingdom. From molluscs to humans, different strains of this fungus affect animals differently, based on how severely the fungus has infected the animal. The clinical signs depend on the species of animal that is infected as well as the strain of fungus it is infected with. This disease is usually found more often in stressed animals after removal from their habitat.[ citation needed ]

Invertebrates

Invertebrates, such as crabs and mollusks, show a variety of clinical signs.

Crabs had increasingly weak motor control, especially in legs and claws, and were lethargic. They had poor balance and tetany, or muscle spasms, in the claws. Finally, they had tissue necrosis, which caused deterioration of the epidermis, connective tissue, heart, hepatopancreas, nervous system, and gills. In severe cases, there was congestion of hemal sinuses, two principal empty areas along the digestive tube and vessels. Mass amounts of yeast-like cells compressed nerve fibers and the gill lamellae were destroyed.[ citation needed ]

Mollusks clinical signs vary from scattered spots of brownish discoloration on the mantle tissues to general deterioration of mussel condition. In severe cases, there were black-bodied mussels with a distinct odor and black yeast cells infected the connective tissues around the gonads and the digestive tract. [13]

Cold-blooded vertebrates

Cold-blooded vertebrates can exhibit an assortment of clinical signs.

Amphibians may show signs of anorexia. Ulcers or nodules in the skin can be found, as well as swelling and lesions of internal organs, including the spleen, liver, and kidney. In extreme cases, neurological disorders and multifocal dermatitis (swelling caused by irritation of the fungus) can occur.

Fish demonstrate signs of lethargy and disoriented swimming. Ulcerative lesions, multiple dark foci in the gills, and non-ulcerative dermal masses may be found. In critical cases, some fish show a variety of inflammatory responses including the formation of microabscesses. Lesions in the brain and kidneys may be present. These fish have abnormal swimming behavior, bulging eyes, and abdominal swelling. [13]

Warm-blooded vertebrates

From birds to equines, phaeohyphomycosis persists and has a massive range of clinical signs throughout differing species. Infected poultry and wild birds can develop neurological disorders and a loss of movement control. They may experience severe torticollis, which are severe muscle spasms that compromise the bird’s ability to hold up its head. Birds can exhibit a loss of balance due to the rigidity of their legs.[ citation needed ]

Cats can exhibit signs of breathing difficulty due to excessive swelling of the nose. Lesions may occur throughout the body, including the brain. [13] Common lesions include ulcerated cutaneous nodules of the digits, pinnae, nasal planum, and nasal/paranasal tissues. [14]

In extreme cases dogs exhibit vision impairment and have deep infections in the nasal cavity, kidneys, and the cerebellum. In dogs, brain infections similar to infections found in humans may occur. Other clinical signs are lesions, abscesses, and severe inflammation throughout the dog’s body.

Ruminants and equines are affected the same way from phaeohyphomycosis. They can exhibit respiratory distress with constant coughing and a fever. They demonstrate signs of anorexia, lethargy, and hypothermia. There may be inflammation, hair loss, scaling, and damage to the cerebellum. [13]

Humans

Humans' clinical signs consist of swelling and eye infections. Nodules underneath the skin, abscesses or cysts may be present. [15] and lesions can run throughout the body, [16] including papules, plaques and granulomatous damage. [16] In extreme cases there can be deep infections within the eyes, bones, heart and central nervous system. [17]

Treatment

Extensive treatments have been used on domestic animals more than on wild animals, probably because infected domestic animals are easier to identify and treat than infected wildlife. Treatment plans and management vary across taxa because this disease tends to affect each species differently. Antifungal drugs are the first line of defense to kill the agents causing phaeohyphomycosis, but despite the significant progress made in the last two decades and a 30% increase in available antifungal drugs since 2000, many drugs are not effective against black fungi. [13] Diseases caused by black fungi are hard to treat because the fungi are very difficult to kill. This high resilience may be contributed to the presence of melanin in their cell walls, as well as the greater similarity to host cells which are both eukaryotes than other pathogens such as bacteria or viruses. Current antifungal agents the fungi are not resistant to are posaconazole, voriconazole, and azole isavuconazole. [13]

In 2006, a free-living eastern box turtle, Terrapene carolina carolina , was found with a form of phaeohyphomycosis and was brought in the Wildlife Center of Virginia. Its symptom was swelling of the right hindfoot; it was diagnosed as having chromomycosis by histopathology. The center provided a series of antimicrobial treatments and a one-month course of 1 mg itraconazole, administered orally once a day. The eastern box turtle was euthanized due to extent of lesional involvement and the caretakers’ belief that the turtle would not be able to survive if placed back in the wild. At necropsy, Exophiala jeanselmei was cultured from a swab of the lesion. [18]

A recent case of a form of phaeohyphomycosis infection was found in a dog in 2011. [19] The Journal of the American Veterinary Medical Association published a case study in which researchers successfully managed an intracranial phaeohyphomycotic fungal granuloma in a one-year-old male Boxer dog. Veterinarians of the Department of Veterinary Clinical Sciences at Tufts University surgically removed the granuloma in the right cerebral hemisphere. The patient was treated with fluconazole for 4 months, followed by voriconazole for 10 months. Based on magnetic resonance imaging and cerebrospinal fluid (CSF) analysis 8 months after the surgery, the male Boxer’s outcome was considered excellent.

Emphasis has been placed on how to manage this disease through careful management practices including: proper handling, preventing crowding situation with animals, and transportation. [13] Both the animals and the environment should be treated thoroughly to hinder the spread and control the fungal infection. This is especially important since humans can also contract this disease.

Research projects and implications

Phaeohyphomycosis is a disease caused by fungi. If given the opportunity, the disease can involve the brain and cause a painful death. There have been multiple reports of this host of fungi, but by the time the disease is recognized, it is usually too late for the animal to be successfully treated. Recent searches of databases show that there are no current projects studying the spread of this fungus in wild animals, though there are documented cases of its occurrence.

In 2005, a five-month-old snow leopard (Uncia uncia) in Europe was diagnosed with phaeohyphomycosis due to Cladophialophora bantiana . This fungus caused spastic paralysis as well as the inability to defecate or urinate. Because of this finding, more researchers are aware of this disease and the fact that it does not just infect the brain, as previously thought, but also other organs and other parts of the nervous system. [20] A Purdue University study in 2011 showed a Huacaya alpaca ( Vicugna pacos ) with the same fungus affected by cerebral phaeohyphomycosis. The eight-year-old animal was the first report of this disease in a camelid ruminant. [21]

In conclusion, phaeohyphomycosis is a highly prolific disease that is caused by multiple genera of fungi. The disease is transmissible through several mediums, including air, wind, and water. Both individual animals and whole populations can be affected by it. Although it does not seem to be an epidemic, it is nonetheless an area of concern and requires much more active research rather than simply reports of terminal or already-dead animals.

See also

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Exophiala jeanselmei is a saprotrophic fungus in the family Herpotrichiellaceae. Four varieties have been discovered: Exophiala jeanselmei var. heteromorpha, E. jeanselmei var. lecanii-corni, E. jeanselmei var. jeanselmei, and E. jeanselmei var. castellanii. Other species in the genus Exophiala such as E. dermatitidis and E. spinifera have been reported to have similar annellidic conidiogenesis and may therefore be difficult to differentiate.

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<i>Cladophialophora bantiana</i> Species of fungus

Cladophialophora bantiana is a melanin producing mold known to cause brain abscesses in humans. It is one of the most common causes of systemic phaeohyphomycosis in mammals. Cladophialophora bantiana is a member of the ascomycota and has been isolated from soil samples from around the world.

Thielavia subthermophila is a ubiquitous, filamentous fungus that is a member of the phylum Ascomycota and order Sordariales. Known to be found on plants of arid environments, it is an endophyte with thermophilic properties, and possesses dense, pigmented mycelium. Thielavia subthermophila has rarely been identified as a human pathogen, with a small number of clinical cases including ocular and brain infections. For treatment, antifungal drugs such as amphotericin B have been used topically or intravenously, depending upon the condition.

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<i>Fonsecaea compacta</i> Species of fungus

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<i>Rhinocladiella mackenziei</i> Species of fungus

Rhinocladiella mackenziei is a deeply pigmented mold that is a common cause of human cerebral phaeohyphomycosis. Rhinocladiella mackenziei was believed to be endemic solely to the Middle East, due to the first cases of infection being limited to the region. However, cases of R. mackenziei infection are increasingly reported from regions outside the Middle East. This pathogen is unique in that the majority of cases have been reported from immunologically normal people.

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Cladophialophora arxii is a black yeast shaped dematiaceous fungus that is able to cause serious phaeohyphomycotic infections. C. arxii was first discovered in 1995 in Germany from a 22-year-old female patient suffering multiple granulomatous tracheal tumours. It is a clinical strain that is typically found in humans and is also capable of acting as an opportunistic fungus of other vertebrates Human cases caused by C. arxii have been reported from all parts of the world such as Germany and Australia.

References

  1. ↑ "ICD-11 - ICD-11 for Mortality and Morbidity Statistics". icd.who.int. Retrieved 30 June 2021.
  2. ↑ Johnstone, Ronald B. (2017). "25. Mycoses and Algal infections". Weedon's Skin Pathology Essentials (2nd ed.). Elsevier. p. 454. ISBN   978-0-7020-6830-0.
  3. 1 2 3 4 5 Milner, Dan A.; Solomon, Isaac (2020). "Phaeohyphomycosis". In Milner, Danny A. (ed.). Diagnostic Pathology: Infectious Diseases. Elsevier. p. 308. ISBN   978-0-323-61138-1.
  4. ↑ Arcobello, Jonathan T.; Revankar, Sanjay G. (February 2020). "Phaeohyphomycosis" . Seminars in Respiratory and Critical Care Medicine. 41 (1): 131–140. doi:10.1055/s-0039-3400957. ISSN   1098-9048. PMID   32000289. S2CID   210983369.
  5. ↑ Chander, Jagdish (2018). "14. Phaeohyphomycosis". Textbook of Medical Mycology (4th ed.). New Delhi: Jaypee Brothers Medical Publishers Ltd. pp. 269–296. ISBN   978-93-86261-83-0.
  6. ↑ Naggie S, Perfect JR (June 2009). "Molds: hyalohyphomycosis, phaeohyphomycosis, and zygomycosis". Clin. Chest Med. 30 (2): 337–53, vii–viii. doi:10.1016/j.ccm.2009.02.009. PMID   19375639.
  7. ↑ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. p. 324. ISBN   978-0-7216-2921-6.
  8. ↑ Boyce RD, Deziel PJ, Otley CC, et al. (December 2009). "Phaeohyphomycosis due to Alternaria species in transplant recipients". Transpl Infect Dis. 12 (3): 242–250. doi:10.1111/j.1399-3062.2009.00482.x. PMID   20002611. S2CID   23751797.
  9. ↑ Umemoto N, Demitsu T, Kakurai M, et al. (October 2009). "Two cases of cutaneous phaeohyphomycosis due to Exophiala jeanselmei: diagnostic significance of direct microscopical examination of the purulent discharge". Clin. Exp. Dermatol. 34 (7): e351–3. doi:10.1111/j.1365-2230.2009.03304.x. PMID   19456770. S2CID   40160899.
  10. ↑ Taj-Aldeen, Saad J.; Almaslamani, Muna; Alkhalf, Abdullatif; Al Bozom, Issam; Romanelli, Anna M.; Wickes, Brian L.; Fothergill, Annette W.; Sutton, Deanna A. (2010-05-01). "Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei (formerly Ramichloridium mackenziei): a taxonomic update and review of the literature". Medical Mycology. 48 (3): 546–556. doi: 10.3109/13693780903383914 . ISSN   1369-3786. PMID   19886775.
  11. ↑ Ajello L, Georg LK, Steigbigel RT, Wang CJ (1974). "A case of phaeophyphomycosis caused by a new species of Philaphora". Mycologia. 66 (3): 490–498. doi:10.1080/00275514.1974.12019630. PMID   4601425. S2CID   34885774.
  12. 1 2 Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi MG (2002). "Disseminated phaeohyphomycosis: review of an emerging mycosis". Clinical Infectious Disease. 34 (4): 467–476. doi: 10.1086/338636 . PMID   11797173.
  13. 1 2 3 4 5 6 7 Seyedmousavi S, Guillot J, de Hoog GS (2013). "Phaeohyphomycoses, emerging opportunistic diseases in animals". Clinical Microbiology Reviews. 26 (1): 19–35. doi: 10.1128/CMR.00065-12 . PMC   3553675 . PMID   23297257.
  14. ↑ "Phaeohyphomycosis". The Merck Veterinary Manual. Retrieved 2019-06-17.
  15. ↑ Hasei M, Takeda K, Anazawa K, Nishibu A, Tanabe H, Mochizuki T (2013). "Case of phaeohyphomycosis producing sporotrichoid lesions". Journal of Dermatology. 40 (8): 638–640. doi:10.1111/1346-8138.12193. PMID   23734832.
  16. 1 2 Cai Q, Lv GX, Jiang YQ, Mei H, Hu SQ, Xu HB, Wu XF, Shen YN, Liu WD (2013). "The first case of phaeohyphomycosis caused by Rhinocladiella basitona in an immunocompetent child in China". Mycopathologia. 176: 101–105. doi:10.1007/s11046-013-9645-0. PMID   23591621.
  17. ↑ Bossler AD, Richter SS, Chavez AJ, Vogelgesang SA, Sutton DA, Grooters AM, Rinaldi MG, de Hoog GS, Pfaller MA (2003). "Exophiala oligosperma causing olecranon bursitis". Journal of Clinical Microbiology. 41 (10): 4779–4782. doi: 10.1128/JCM.41.10.4779-4782.2003 . PMC   254319 . PMID   14532219.
  18. ↑ Joyner PH, Shreve AA, Spahr J, Fountain AL, Sleeman JM (2006). "Phaeohyphomycosis in a free-living eastern box turtle (Terrapene carolina carolina)". Journal of Wildlife Diseases. 42 (4): 883–888. doi: 10.7589/0090-3558-42.4.883 . PMID   17255461.
  19. ↑ Bently RT, Faissler D, Sutherland-Smith J (2011). "Successful management of an intracranial phaeohypomycotic fungal granuloma in a dog". Journal of the American Veterinary Medical Association. 239 (4): 480–485. doi: 10.2460/javma.239.4.480 . PMID   21838585.
  20. ↑ Janovsky M, Gröne A, Ciardo D, Völlm J, Burnens A, Fatzer R, Bacciarini LN (2006). "Phaeohyphomycisis in a snow leopard (Uncia uncia) due to Cladophialophora bantiana". Journal of Comparative Pathology. 134 (2–3): 245–248. doi:10.1016/j.jcpa.2005.09.006. PMID   16542676.
  21. ↑ Frank C, Vemulapalli R, Lin T (2011). "Cerebral phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya alpaca (Vicugna pacos)". Journal of Comparative Pathology. 145 (4): 410–413. doi:10.1016/j.jcpa.2011.02.003. PMID   21511274.
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