Onychomycosis

Case study

By Steven Goldstein, DPM; Basem Halaka, DPM; David Vance, DPM; Jason Weslosky, DPM

History of Present Illness

The patient is a 62 year old male with a 2 year history of thickened, elongated, and yellow discolored nails of the hallux bilateral. The nails appear dystrophic with evidence of subungual debris. The patient does not recall any significant trauma to the nails but does admit to uncomfortable rubbing of the bilateral hallux nails in his shoes. The patient does not have any other contributing medical history.

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Differential Diagnosis

Diagnostic considerations in this case include onychomycosis, trauma, psoriasis, lichen planus, chronic paronychia, and dermatitis.

Work-up

The bilateral nails were debrided and multiple keratogenous samples were sent for analysis (histopathology and PCR). Care was taken to remove debri subungually as well as portions of the proximal nail plate.

Histopathology and Molecular Analysis

Identified in this study were histopathologic features of acute and chronic micro-trauma as well as onychomycosis. Fungal elements were demonstrated with both PAS and GMS stains. Fontana Masson staining was performed as well and was negative for melanin.   PCR testing was performed and was able to identify the organism, a saprophyte of the Fusarium genus.

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Discussion

The most prevalent risk factor for developing onychomycosis is advanced age. Other risk factors include warm climate, peripheral vascular disease, and diabetes mellitus. Immunocompromised conditions are also thought to be linked to the prevalence of onychomycosis, especially those caused by non-dermatophyte species. It should also be noted that onychomycosis and nail trauma often coexist, with nail trauma often being a predisposing factor for the development of onychomycosis.

While many onychomycosis cases are caused by dermatophytes, it is important to note that there are also cases involving yeasts and saprophytic species, thus proper identification is key to appropriate treatment .  In this case, the isolated pathogen was a saphrophyte of the Fusarium genus.  The most opportunistic of this species include F. solani complex, F. oxsporum complex and F. fujikorai complex.  Most commonly these species cause onychomycosis in tropical countries however they are also present in temperate and artic climates with recent reports of Fusarium as a common pathogen in central European countries.

Treatment

Multiple treatment options exist for onychomycosis. Medications exist in both oral and topical forms. Furthermore other options for treatment such as mechanical and chemical avulsion exist. Topical treatments are often reserved for superficial white onychomycosis or distal subungual onychomycosis affecting less than 50 percent of the nail surface. Tolnaftate and Ciclopirox are common topical therapies employed. Topical urea may be used in conjunction with topical therapies to act as a vehicle to increase penetration of the medication into the nail unit. Oral treatment options are often a better option for proximal subungual onychomycosis or onychomycosis that is involving more than 50% of the nail plate. Terbinafine, Itraconazole, Fluconazole are all oral medication options for treating this condition. Terbinafine is perhaps the most commonly prescribed and is useful against both dermatophyte and some non-dermatophyte species. Itraconazole has greater effect toward non-dermatophyte species however it must be used with caution as it is contraindicated in pregnancy. Fluconazole is another option however therapeutic treatment times remain longer when compared to other oral medications. Speciation of the organism may guide to the most effective oral therapy for the specific organism. Furthermore, both mechanical and chemical debridement remain as options for treating onychomycosis. Chemical debridement often consists of applying a compound containing urea to the nail. Depending on the exact formulation of the compound, this may be done under occlusion or without occlusion. It should be noted that chemical debridement alone is not effective and often has to be combined with other treatment modalities. Lastly, mechanical debridement or avulsion of the nail plate remains a viable option especially in cases where previously mentioned treatment modalities have failed. However care must be taken in patients with comorbidities such as peripheral vascular disease, diabetes, or infection.

Laboratory Testing Modalities for Onychomycosis

There are multiple tests that can be performed to evaluate for the presence of fungi in a tissue specimen.  Some of the commonly performed tests include the periodic acid-Schiff(PAS) reaction, Grocott methenamine silver(GMS) stain, Fontana-Masson stain, culture, and polymerase chain reaction(PCR) assay.  PAS is a periodic acid and Schiff reagent stain.  It is useful in detecting carbohydrates within the cell walls of living fungi. In PAS testing, the aldehyde groups in the fungal cell walls react with the stain to produce a magenta color.  The GMS stain is a chromic acid and bisulfite stain.  It is also useful in detecting fungal elements; however it is generally able to produce better staining contrast as well as improved detection of degenerated or dead fungi.  The Fontana-Masson stain highlights melanin pigment in certain fungal organisms along with melanin pigment deposition in various conditions.  Fontana-Masson has shown variable staining among different types of fungi; however, higher quantity staining within the fungal organisms favors dematiaceous fungi (pigmented saprophytic mold).  Fungal culture can be performed on fresh tissue but suffers from long turn-around time (28 days) and high false negative results.  PCR Assay detects the genetic material of fungi.  Advantages of PCR include rapid (1-2 day) turn-around, a minimum of 25% higher sensitivity than culture, and the ability to identify the specific fungal species.

References:

Werner B, Antunes A. Microscopic examination of normal nail clippings. Dermatol Pract Concept. 2013;3(3):9-14. Published 2013 Jul 31.

Ranawaka RR, Nagahawatte A, Gunasekara TA. Fusarium onychomycosis: prevalence, clinical presentations, response to itraconazole and terbinafine pulse therapy, and 1-year follow up in nine cases. Int J Dermatol. 2015;54(11):1275-1282.

Rammlmair A, Muhlethaler K, Haneke E. Fusarium onychomycoses in Switzerland-A mycological and histopathological study. Mycoses. 2019;62(10):928-931.

Gupta AK, Simpson FC. New therapeutic options for onychomycosis. Expert Opin Pharmacother. 2012;13:1131-1142.

Gupta AK, Kohli Y. In vitro susceptibility testing of ciclopirox,terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and in vitro evaluation of combination antifungalactivity. Br J Dermatol. 2003;149:296-305.

Figueiredo VT, de Assis Santos D, Resende MA, et al. Identificationand in vitro antifungal susceptibility testing of 200 clinical isolates of Candida spp. responsible for fingernail infections. Mycopathologia. 2007;164:27-33.

Emam, Sherin, and Osama El-salam. “Real-Time PCR: a Rapid and Sensitive Method for Diagnosis of Dermatophyte Induced Onychomycosis, a Comparative Study.” Alexandria Journal of Medicine, 29 Aug. 2015.

D’Hue, Zandra, et al. “GMS Is Superior to PAS for Diagnosis of Onychomycosis.” Journal of Cutaneous Pathology, 14 Aug. 2007.

West, Kelly, et al. “Fontana-Masson Stain in Fungal Infections.” Dermatopathology, Dec. 2017.




What podiatrists need to know about dermatopathologists

Q&A with two Bako Diagnostics dermatopathologists:

Kim Whisenant, M.D., and Carolina Montes, M.D. on partnering with podiatrists

Carolina M. Montes, M.D.
Carolina M. Montes, M.D.Dermatopatologist
Kim Whisenant, M.D.
Kim Whisenant, M.D.Dermatopatologist

Q. What is the importance of podiatrists being familiar with pathology, specifically dermatopathology?

A. Dr. Montes:
The skin is the largest organ of the body, and many medical specialties, including podiatry, come in contact with disorders of the skin. Lesions that appear on the skin, including the foot, can also be a manifestation of internal systemic disease. Consequently, it’s important for clinicians to be familiar with both inflammatory and neoplastic processes of the skin. Dermatopathology is the subspecialty of pathology that provides this knowledge.

A. Dr. Whisenant:
Because many dermatologic lesions – both benign and malignant – are commonly found on the lower extremities, podiatrists have a unique opportunity to evaluate patients and detect these lesions early on. The best way to detect these lesions is to be familiar with the dermatologic and pathologic presentation, and generate a clinical differential diagnosis, properly biopsy the lesion, and receive a more specific diagnosis.

Q. Your team has partnered with thousands of podiatrists to diagnose and treat the lower extremity. When should a podiatrist reach out to a dermatopathologist?

A. Dr. Whisenant:
If a lesion is biopsied incorrectly or sent in the wrong solution — or worse — in no solution, and allowed to air-dry, it can be difficult and sometimes impossible to diagnose. Podiatrists should work with a dermatopathologist when they have questions on specimen collection. The proper specimen collection and submission process is critical to getting to the right treatment.

A. Dr. Montes:
When reviewing Bako’s detailed report, podiatrists are encouraged to ask any questions pertaining to the diagnosis or recommended treatment. Our reporting dermatopathologists are easily accessible and eager to provide the best service.

Q. What should podiatrists consider when submitting a specimen to the lab for analysis and dermatopathologist reading and interpretation?

A. Dr. Whisenant:
When submitting a specimen, be sure the basic requisition forms are complete and add as much specific information as possible – biopsy site, lesion location/description/history, clinical differential diagnosis. In addition, uploading images of your patient’s lesion can be valuable to diagnosis and treatment suggestions. Upload capabilities are available for podiatrists through the Bako Diagnostics web portal.

A. Dr. Montes:
Understanding the appropriate scenarios to use the varying specimen collection techniques (punch, shave, scraping, excision, avulsion, etc.), the correct preservatives to use, and how to avoid sampling artifact – are all key to proper submission and diagnosis. Bako Diagnostics has published the “Lower Extremity Biopsy Techniques,” a Practice Essentials guide for the podiatric medical professional. This is helpful in identifying the best practices for specimen collection. A complimentary copy is available to all podiatrists at https://bit.ly/3sY6yks.




Blastomycosis

By Morgan Baxter, DPM, Aron Block, DPM, Lillian Youhkana, DPM

Blastomycosis is a type of fungal infection that can be acquired from inhaling fungal spores

History

A 53 year old healthy male presents to clinic with concerns of a rash involving raised bumps for about a month. He thought it was a cluster of warts, but has not had any relief with over the counter topical medications. He does mention that about a month ago, he was raking leaves barefoot. The bumps are not painful but have started to leak and have not gone away. He resides in Ohio near Lake Erie.

A punch biopsy of a representative lesion was submitted.

Histologic findings:

Verrucous lesion with pseudoepitheliomatous hyperplasia and a polymorphous dermal inflammatory cell infiltrate with scattered giant cells and neutrophils with occasional microabcesses.  PAS and GMS stains are positive for thick walled yeasts with broad based budding.  Yeasts, which measure 7-15 micrometers are found in the center of the abscess and sometimes in the giant cells.

Diagnosis

Blastomycosis

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Differential Diagnosis

Other cutaneous infections can mimic cutaneous blastomycosis including other endemic mycosis such as histoplasmosis and coccidioidomycosis. It has been found that cutaneous blastomycosis may very closely resemble pyoderma gangrenosum or keratoacantoma or malignancies such as basal cell carcinoma or squamous cell carcinoma. For proper diagnosis a skin biopsy is vital in differentiating blastomycosis infection from these other diseases.

Discussion

Blastomycosis is a type of fungal infection that can be acquired from inhaling fungal spores from the air.   It is found in the United States and Canada and is concentrated in the Ohio and Mississippi river valleys and the Great Lakes region.  Blastomycosis is typically found in soil and decaying organic matter. It manifests as a primary lung infection in the majority of cases.  In individuals with weakened immune systems, the infection can spread to other areas of the body such as the skin. Following pneumonia, cutaneous lesions are the next most common manifestation of blastomycosis. The skin lesions are either verrucous or ulcerative. Bone, prostatic and CNS blastomycosis are also fairly common presentations of this infection. The disease is often misdiagnosed, particularly as malignancy. Search for the organism by microscopy and culture should be considered, even in those with a classic presentation of other illnesses. Most people with blastomycosis will need treatment with prescription antifungal medications. Depending on the severity of the infection, the course of treatment can range from six months to a year. Mild and moderate fungal infections involving the skin and lungs are best treated with Itraconazole. Amphotericin B should be used in severe infections involving the lungs. In conclusion, a thorough history including a geographical location is imperative to help make the accurate diagnosis of a blastomycosis infection.

References:

Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, et al. (2008) Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clinical Infectious Diseases 46: 1801–1812

Larson DM, Eckman MR, Alber RL, Goldschmidt VG. Primary cutaneous (inoculation) blastomycosis: an occupational hazard to pathologist. Am J Clinc Pathol. 1983;79(2):253–255.

McBride, J. A., Gauthier, G. M., & Klein, B. S. (2017). Clinical Manifestations and Treatment of Blastomycosis. Clinics in chest medicine, 38(3), 435–449. doi:10.1016/j.ccm.2017.04.006

Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010

Smith JA, Riddell J, IV, Kauffman CA. Cutaneous manifestations of endemic mycoses. Curr Infect Dis Rep. 2013;15(5):440–449