Hair & Nails

First described by Fetsch et al¹ in 2001, superficial acral fibromyxoma (SAFM) is a rare fibromyxoid mesenchymal tumor that typically affects the fingers and toes with frequent involvement of the nail unit. It is not widely recognized and remains poorly understood. We describe a series of 3 cases of SAFM encountered at our institution and provide a review of the literature on this unique tumor.

Case Reports

Patient 1

A 35-year-old man presented for treatment of a “wart” on the right fifth toe that had increased in size over the last year. He reported that the lesion was mildly painful and occasionally bled or drained clear fluid. He also noted cracking of the nail plate on the same toe. Physical examination revealed a firm, flesh-colored, 3-mm dermal papule on the proximal nail fold of the right fifth toe with subtle flattening of the underlying nail plate (Figure 1). The patient underwent biopsy of the involved proximal nail fold. Histopathology revealed a proliferation of small oval and spindle cells arranged in fascicles and bundles in the dermis (Figure 2). There was extensive mucin deposition associated with the spindle cell proliferation. Additionally, spindle cells and mucin surrounded and entrapped collagen bundles on the periphery of the lesion. Lesional cells were diffusely positive for CD34 and extended to the deep surgical margin (Figure 3). S-100 and factor XIIIa stains were negative. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Figure 1. Firm dermal papule on the proximal nail fold of the right fifth toe with associated nail plate dystrophy. Figure 2. Small oval and spindle cells arranged in fascicles and bundles in the dermis, with extensive mucin deposition and collagen trapping (H&E, original magnification ×100). Figure 3. Tumor cells were positive on CD34 staining (original magnification ×40). Figure 4. Dermal stellate spindle cells arranged in a loose fascicular pattern with marked mucin deposition (H&E, original magnification ×400).

Patient 2

A 47-year-old man presented with an asymptomatic growth on the left fourth toe that had increased in size over the last year. Physical examination revealed an 8-mm, firm, fleshy, flesh-colored, smooth and slightly pedunculated papule on the distal aspect of the left fourth toe. The nail plate and periungual region were not involved. A shave biopsy of the papule was obtained. Histopathology demonstrated dermal stellate spindle cells arranged in a loose fascicular pattern with marked mucin deposition throughout the dermis (Figure 4). Lesional cells were positive for CD34. An S-100 stain highlighted dermal dendritic cells, but lesional cells were negative. No further excision was undertaken, and there was no evidence of recurrence at 1-year follow-up. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Patient 3

A 45-year-old woman presented with asymptomatic distal onycholysis of the right thumbnail of 1 year’s duration. She denied any history of trauma, and no bleeding or pigmentary changes were noted. Physical examination revealed a 5-mm flesh-colored papule on the hyponychium of the right thumb with focal onycholysis (Figure 5). A wedge biopsy of the lesion was performed. Histopathology showed an intradermal nodular proliferation of bland spindle cells arranged in loose fascicles and bundles and embedded in a myxoid stroma (Figure 6). CD34 staining strongly highlighted lesional cells. S-100 and neurofilament stains were negative. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Comment

Clinically, SAFM typically presents as a slow-growing solitary nodule on the distal fingers or toes. The great toe is the most commonly affected digit, and the tumor may be subungual in up to two-thirds of cases.¹ Unusual locations, such as the heel, also have been reported.² Onset typically occurs in the fifth or sixth decade, and there is an approximately 2-fold higher incidence in men than women.^1-3

Histopathologically, SAFM is a characteristically well-circumscribed but unencapsulated dermal tumor composed of spindle and stellate cells in a loose storiform or fascicular arrangement embedded in a myxoid, myxocollagenous, or collagenous stroma.⁴ The tumor often occupies the entire dermis and may extend into the subcutis or occasionally the underlying fascia and bone.^4,5 Mast cells often are prominent, and microvascular accentuation also may be seen. Inflammatory infiltrates and multinucleated giant cells typically are not seen.⁶ Although 2 cases of atypical SAFM have been described,² cellular atypia is not a characteristic feature of SAFM.

The immunohistochemical profile of SAFM is characterized by diffuse or focal expression of CD34, focal expression of epithelial membrane antigen (EMA), CD99 expression, and varying numbers of factor XIIIa–positive histiocytes.^2,3 Positive staining for vimentin also is common. Staining typically is negative for S-100, human melanoma black 45, keratin, smooth muscle actin, and desmin.

The standard treatment of SAFM is complete local resection of the tumor, though some patients have been treated with partial excision or biopsy and partial or complete digital amputation.¹ Local recurrence may occur in up to 20% of cases; however, approximately two-thirds of the reported recurrences in the literature occurred after incomplete tumor excision.^1,2 It may be more appropriate to consider these cases as persistent rather than recurrent tumors. Superficial acral fibromyxoma is considered a benign tumor, with no known cases of metastases.⁴

Figure 5. A firm flesh-colored papule on the hyponychium of the right thumb prior to biopsy. Figure 6. Intradermal nodular proliferation of bland spindle cells arranged in loose fascicles and bundles and embedded in a myxoid stroma (H&E, original magnification ×40).

A broad differential diagnosis exists for SAFM and it can be difficult to differentiate it from a wide variety of benign and malignant tumors that may be seen on the nail unit and distal extremities (Table). Myxoid neurofibromas typically present as solitary lesions on the hands and feet. Similar to SAFM, myxoid neurofibromas are unencapsulated dermal tumors composed of spindle-shaped cells in which mast cells often are conspicuous.^2,7 However, tumor cells in myxoid neurofibromas are S-100 positive, and the lesions typically do not show vasculature accentuation.^4,7

Sclerosing perineuriomas are benign fibrous tumors of the fingers and palms. Histopathologically, bland spindle cells arranged in fascicles and whorls are observed in a hyalinized collagen matrix.⁸ Immunohistochemically, sclerosing perineuriomas are positive for EMA and negative for S-100, but unlike SAFM, these tumors usually are CD34 negative.⁸

Superficial angiomyxomas typically are located on the head and neck but also may be found in other locations such as the trunk. They present as cutaneous papules or polypoid lesions. Histopathologically, superficial angiomyxomas are poorly circumscribed with a lobular pattern. Spindle-shaped fibroblasts exist in a myxoid matrix with neutrophils and thin-walled capillaries. The fibroblasts are variably positive for CD34 but also are S-100 positive.^1,9

Myxoid dermatofibrosarcoma protuberans is a rare, locally aggressive, mesenchymal tumor of the skin and subcutis² that typically presents on the trunk, proximal extremities, or head and neck; occurrence on the fingers or toes is exceedingly rare.^2,10 Histopathologically, a myxoid stroma contains sheets of bland spindle-shaped cells with minimal to no atypia, sometimes arranged in a storiform pattern. The tumor characteristically invades deeply into the subcutaneous tissues. CD34 is characteristically positive and S-100 is negative.^2,10

Low-grade myxofibrosarcoma is a soft tissue sarcoma easily confused with other spindle cell tumors. It is one of the most common sarcomas in adults but rarely arises in acral areas.² It is characterized by a nodular growth pattern with marked nuclear atypia and perivascular clustering of tumor cells. CD34 staining may be positive in some cases.¹¹

Similar to SAFM, myxoinflammatory fibroblastic sarcoma has a predilection for the extremities.⁴ However, it typically presents as a subcutaneous mass and has no documented tendency for nail bed involvement. Also unlike SAFM, it has a remarkable inflammatory infiltrate and characteristic virocyte or Reed-Sternberg cells.¹²

Acquired digital fibrokeratomas are benign neoplasms that occur on fingers and toes; the classic clinical presentation is a solitary smooth nodule or dome, often with a characteristic projecting configuration and horn shape.¹ Histopathologically, these tumors are paucicellular with thick, vertically oriented, interwoven collagen bundles; cells may be positive for CD34 but are negative for EMA.^1,13 Related to acquired digital fibrokeratomas are Koenen tumors, which share a similar histology but are distinguished by their clinical characteristics. For example, Koenen tumors tend to be multifocal and are strongly associated with tuberous sclerosis. These tumors also have a tendency to recur.¹

Conclusion

Our report of 3 typical cases of SAFM highlights the need to keep this increasingly recognized and well-defined clinicopathological entity in the differential for slow-growing tumors in acral locations, particularly those in the periungual and subungual regions.

First described by Fetsch et al¹ in 2001, superficial acral fibromyxoma (SAFM) is a rare fibromyxoid mesenchymal tumor that typically affects the fingers and toes with frequent involvement of the nail unit. It is not widely recognized and remains poorly understood. We describe a series of 3 cases of SAFM encountered at our institution and provide a review of the literature on this unique tumor.

Case Reports

Patient 1

A 35-year-old man presented for treatment of a “wart” on the right fifth toe that had increased in size over the last year. He reported that the lesion was mildly painful and occasionally bled or drained clear fluid. He also noted cracking of the nail plate on the same toe. Physical examination revealed a firm, flesh-colored, 3-mm dermal papule on the proximal nail fold of the right fifth toe with subtle flattening of the underlying nail plate (Figure 1). The patient underwent biopsy of the involved proximal nail fold. Histopathology revealed a proliferation of small oval and spindle cells arranged in fascicles and bundles in the dermis (Figure 2). There was extensive mucin deposition associated with the spindle cell proliferation. Additionally, spindle cells and mucin surrounded and entrapped collagen bundles on the periphery of the lesion. Lesional cells were diffusely positive for CD34 and extended to the deep surgical margin (Figure 3). S-100 and factor XIIIa stains were negative. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Figure 1. Firm dermal papule on the proximal nail fold of the right fifth toe with associated nail plate dystrophy. Figure 2. Small oval and spindle cells arranged in fascicles and bundles in the dermis, with extensive mucin deposition and collagen trapping (H&E, original magnification ×100). Figure 3. Tumor cells were positive on CD34 staining (original magnification ×40). Figure 4. Dermal stellate spindle cells arranged in a loose fascicular pattern with marked mucin deposition (H&E, original magnification ×400).

Patient 2

A 47-year-old man presented with an asymptomatic growth on the left fourth toe that had increased in size over the last year. Physical examination revealed an 8-mm, firm, fleshy, flesh-colored, smooth and slightly pedunculated papule on the distal aspect of the left fourth toe. The nail plate and periungual region were not involved. A shave biopsy of the papule was obtained. Histopathology demonstrated dermal stellate spindle cells arranged in a loose fascicular pattern with marked mucin deposition throughout the dermis (Figure 4). Lesional cells were positive for CD34. An S-100 stain highlighted dermal dendritic cells, but lesional cells were negative. No further excision was undertaken, and there was no evidence of recurrence at 1-year follow-up. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Patient 3

A 45-year-old woman presented with asymptomatic distal onycholysis of the right thumbnail of 1 year’s duration. She denied any history of trauma, and no bleeding or pigmentary changes were noted. Physical examination revealed a 5-mm flesh-colored papule on the hyponychium of the right thumb with focal onycholysis (Figure 5). A wedge biopsy of the lesion was performed. Histopathology showed an intradermal nodular proliferation of bland spindle cells arranged in loose fascicles and bundles and embedded in a myxoid stroma (Figure 6). CD34 staining strongly highlighted lesional cells. S-100 and neurofilament stains were negative. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Comment

Clinically, SAFM typically presents as a slow-growing solitary nodule on the distal fingers or toes. The great toe is the most commonly affected digit, and the tumor may be subungual in up to two-thirds of cases.¹ Unusual locations, such as the heel, also have been reported.² Onset typically occurs in the fifth or sixth decade, and there is an approximately 2-fold higher incidence in men than women.^1-3

Histopathologically, SAFM is a characteristically well-circumscribed but unencapsulated dermal tumor composed of spindle and stellate cells in a loose storiform or fascicular arrangement embedded in a myxoid, myxocollagenous, or collagenous stroma.⁴ The tumor often occupies the entire dermis and may extend into the subcutis or occasionally the underlying fascia and bone.^4,5 Mast cells often are prominent, and microvascular accentuation also may be seen. Inflammatory infiltrates and multinucleated giant cells typically are not seen.⁶ Although 2 cases of atypical SAFM have been described,² cellular atypia is not a characteristic feature of SAFM.

The immunohistochemical profile of SAFM is characterized by diffuse or focal expression of CD34, focal expression of epithelial membrane antigen (EMA), CD99 expression, and varying numbers of factor XIIIa–positive histiocytes.^2,3 Positive staining for vimentin also is common. Staining typically is negative for S-100, human melanoma black 45, keratin, smooth muscle actin, and desmin.

The standard treatment of SAFM is complete local resection of the tumor, though some patients have been treated with partial excision or biopsy and partial or complete digital amputation.¹ Local recurrence may occur in up to 20% of cases; however, approximately two-thirds of the reported recurrences in the literature occurred after incomplete tumor excision.^1,2 It may be more appropriate to consider these cases as persistent rather than recurrent tumors. Superficial acral fibromyxoma is considered a benign tumor, with no known cases of metastases.⁴

Figure 5. A firm flesh-colored papule on the hyponychium of the right thumb prior to biopsy. Figure 6. Intradermal nodular proliferation of bland spindle cells arranged in loose fascicles and bundles and embedded in a myxoid stroma (H&E, original magnification ×40).

A broad differential diagnosis exists for SAFM and it can be difficult to differentiate it from a wide variety of benign and malignant tumors that may be seen on the nail unit and distal extremities (Table). Myxoid neurofibromas typically present as solitary lesions on the hands and feet. Similar to SAFM, myxoid neurofibromas are unencapsulated dermal tumors composed of spindle-shaped cells in which mast cells often are conspicuous.^2,7 However, tumor cells in myxoid neurofibromas are S-100 positive, and the lesions typically do not show vasculature accentuation.^4,7

Sclerosing perineuriomas are benign fibrous tumors of the fingers and palms. Histopathologically, bland spindle cells arranged in fascicles and whorls are observed in a hyalinized collagen matrix.⁸ Immunohistochemically, sclerosing perineuriomas are positive for EMA and negative for S-100, but unlike SAFM, these tumors usually are CD34 negative.⁸

Superficial angiomyxomas typically are located on the head and neck but also may be found in other locations such as the trunk. They present as cutaneous papules or polypoid lesions. Histopathologically, superficial angiomyxomas are poorly circumscribed with a lobular pattern. Spindle-shaped fibroblasts exist in a myxoid matrix with neutrophils and thin-walled capillaries. The fibroblasts are variably positive for CD34 but also are S-100 positive.^1,9

Myxoid dermatofibrosarcoma protuberans is a rare, locally aggressive, mesenchymal tumor of the skin and subcutis² that typically presents on the trunk, proximal extremities, or head and neck; occurrence on the fingers or toes is exceedingly rare.^2,10 Histopathologically, a myxoid stroma contains sheets of bland spindle-shaped cells with minimal to no atypia, sometimes arranged in a storiform pattern. The tumor characteristically invades deeply into the subcutaneous tissues. CD34 is characteristically positive and S-100 is negative.^2,10

Low-grade myxofibrosarcoma is a soft tissue sarcoma easily confused with other spindle cell tumors. It is one of the most common sarcomas in adults but rarely arises in acral areas.² It is characterized by a nodular growth pattern with marked nuclear atypia and perivascular clustering of tumor cells. CD34 staining may be positive in some cases.¹¹

Similar to SAFM, myxoinflammatory fibroblastic sarcoma has a predilection for the extremities.⁴ However, it typically presents as a subcutaneous mass and has no documented tendency for nail bed involvement. Also unlike SAFM, it has a remarkable inflammatory infiltrate and characteristic virocyte or Reed-Sternberg cells.¹²

Acquired digital fibrokeratomas are benign neoplasms that occur on fingers and toes; the classic clinical presentation is a solitary smooth nodule or dome, often with a characteristic projecting configuration and horn shape.¹ Histopathologically, these tumors are paucicellular with thick, vertically oriented, interwoven collagen bundles; cells may be positive for CD34 but are negative for EMA.^1,13 Related to acquired digital fibrokeratomas are Koenen tumors, which share a similar histology but are distinguished by their clinical characteristics. For example, Koenen tumors tend to be multifocal and are strongly associated with tuberous sclerosis. These tumors also have a tendency to recur.¹

Conclusion

Our report of 3 typical cases of SAFM highlights the need to keep this increasingly recognized and well-defined clinicopathological entity in the differential for slow-growing tumors in acral locations, particularly those in the periungual and subungual regions.

First described by Fetsch et al¹ in 2001, superficial acral fibromyxoma (SAFM) is a rare fibromyxoid mesenchymal tumor that typically affects the fingers and toes with frequent involvement of the nail unit. It is not widely recognized and remains poorly understood. We describe a series of 3 cases of SAFM encountered at our institution and provide a review of the literature on this unique tumor.

Case Reports

Patient 1

A 35-year-old man presented for treatment of a “wart” on the right fifth toe that had increased in size over the last year. He reported that the lesion was mildly painful and occasionally bled or drained clear fluid. He also noted cracking of the nail plate on the same toe. Physical examination revealed a firm, flesh-colored, 3-mm dermal papule on the proximal nail fold of the right fifth toe with subtle flattening of the underlying nail plate (Figure 1). The patient underwent biopsy of the involved proximal nail fold. Histopathology revealed a proliferation of small oval and spindle cells arranged in fascicles and bundles in the dermis (Figure 2). There was extensive mucin deposition associated with the spindle cell proliferation. Additionally, spindle cells and mucin surrounded and entrapped collagen bundles on the periphery of the lesion. Lesional cells were diffusely positive for CD34 and extended to the deep surgical margin (Figure 3). S-100 and factor XIIIa stains were negative. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Figure 1. Firm dermal papule on the proximal nail fold of the right fifth toe with associated nail plate dystrophy. Figure 2. Small oval and spindle cells arranged in fascicles and bundles in the dermis, with extensive mucin deposition and collagen trapping (H&E, original magnification ×100). Figure 3. Tumor cells were positive on CD34 staining (original magnification ×40). Figure 4. Dermal stellate spindle cells arranged in a loose fascicular pattern with marked mucin deposition (H&E, original magnification ×400).

Patient 2

A 47-year-old man presented with an asymptomatic growth on the left fourth toe that had increased in size over the last year. Physical examination revealed an 8-mm, firm, fleshy, flesh-colored, smooth and slightly pedunculated papule on the distal aspect of the left fourth toe. The nail plate and periungual region were not involved. A shave biopsy of the papule was obtained. Histopathology demonstrated dermal stellate spindle cells arranged in a loose fascicular pattern with marked mucin deposition throughout the dermis (Figure 4). Lesional cells were positive for CD34. An S-100 stain highlighted dermal dendritic cells, but lesional cells were negative. No further excision was undertaken, and there was no evidence of recurrence at 1-year follow-up. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Patient 3

A 45-year-old woman presented with asymptomatic distal onycholysis of the right thumbnail of 1 year’s duration. She denied any history of trauma, and no bleeding or pigmentary changes were noted. Physical examination revealed a 5-mm flesh-colored papule on the hyponychium of the right thumb with focal onycholysis (Figure 5). A wedge biopsy of the lesion was performed. Histopathology showed an intradermal nodular proliferation of bland spindle cells arranged in loose fascicles and bundles and embedded in a myxoid stroma (Figure 6). CD34 staining strongly highlighted lesional cells. S-100 and neurofilament stains were negative. The diagnosis of SAFM was made based on the acral location, histopathologic appearance, and immunohistochemical profile of the tumor.

Comment

Clinically, SAFM typically presents as a slow-growing solitary nodule on the distal fingers or toes. The great toe is the most commonly affected digit, and the tumor may be subungual in up to two-thirds of cases.¹ Unusual locations, such as the heel, also have been reported.² Onset typically occurs in the fifth or sixth decade, and there is an approximately 2-fold higher incidence in men than women.^1-3

Histopathologically, SAFM is a characteristically well-circumscribed but unencapsulated dermal tumor composed of spindle and stellate cells in a loose storiform or fascicular arrangement embedded in a myxoid, myxocollagenous, or collagenous stroma.⁴ The tumor often occupies the entire dermis and may extend into the subcutis or occasionally the underlying fascia and bone.^4,5 Mast cells often are prominent, and microvascular accentuation also may be seen. Inflammatory infiltrates and multinucleated giant cells typically are not seen.⁶ Although 2 cases of atypical SAFM have been described,² cellular atypia is not a characteristic feature of SAFM.

The immunohistochemical profile of SAFM is characterized by diffuse or focal expression of CD34, focal expression of epithelial membrane antigen (EMA), CD99 expression, and varying numbers of factor XIIIa–positive histiocytes.^2,3 Positive staining for vimentin also is common. Staining typically is negative for S-100, human melanoma black 45, keratin, smooth muscle actin, and desmin.

The standard treatment of SAFM is complete local resection of the tumor, though some patients have been treated with partial excision or biopsy and partial or complete digital amputation.¹ Local recurrence may occur in up to 20% of cases; however, approximately two-thirds of the reported recurrences in the literature occurred after incomplete tumor excision.^1,2 It may be more appropriate to consider these cases as persistent rather than recurrent tumors. Superficial acral fibromyxoma is considered a benign tumor, with no known cases of metastases.⁴

Figure 5. A firm flesh-colored papule on the hyponychium of the right thumb prior to biopsy. Figure 6. Intradermal nodular proliferation of bland spindle cells arranged in loose fascicles and bundles and embedded in a myxoid stroma (H&E, original magnification ×40).

A broad differential diagnosis exists for SAFM and it can be difficult to differentiate it from a wide variety of benign and malignant tumors that may be seen on the nail unit and distal extremities (Table). Myxoid neurofibromas typically present as solitary lesions on the hands and feet. Similar to SAFM, myxoid neurofibromas are unencapsulated dermal tumors composed of spindle-shaped cells in which mast cells often are conspicuous.^2,7 However, tumor cells in myxoid neurofibromas are S-100 positive, and the lesions typically do not show vasculature accentuation.^4,7

Sclerosing perineuriomas are benign fibrous tumors of the fingers and palms. Histopathologically, bland spindle cells arranged in fascicles and whorls are observed in a hyalinized collagen matrix.⁸ Immunohistochemically, sclerosing perineuriomas are positive for EMA and negative for S-100, but unlike SAFM, these tumors usually are CD34 negative.⁸

Superficial angiomyxomas typically are located on the head and neck but also may be found in other locations such as the trunk. They present as cutaneous papules or polypoid lesions. Histopathologically, superficial angiomyxomas are poorly circumscribed with a lobular pattern. Spindle-shaped fibroblasts exist in a myxoid matrix with neutrophils and thin-walled capillaries. The fibroblasts are variably positive for CD34 but also are S-100 positive.^1,9

Myxoid dermatofibrosarcoma protuberans is a rare, locally aggressive, mesenchymal tumor of the skin and subcutis² that typically presents on the trunk, proximal extremities, or head and neck; occurrence on the fingers or toes is exceedingly rare.^2,10 Histopathologically, a myxoid stroma contains sheets of bland spindle-shaped cells with minimal to no atypia, sometimes arranged in a storiform pattern. The tumor characteristically invades deeply into the subcutaneous tissues. CD34 is characteristically positive and S-100 is negative.^2,10

Low-grade myxofibrosarcoma is a soft tissue sarcoma easily confused with other spindle cell tumors. It is one of the most common sarcomas in adults but rarely arises in acral areas.² It is characterized by a nodular growth pattern with marked nuclear atypia and perivascular clustering of tumor cells. CD34 staining may be positive in some cases.¹¹

Similar to SAFM, myxoinflammatory fibroblastic sarcoma has a predilection for the extremities.⁴ However, it typically presents as a subcutaneous mass and has no documented tendency for nail bed involvement. Also unlike SAFM, it has a remarkable inflammatory infiltrate and characteristic virocyte or Reed-Sternberg cells.¹²

Acquired digital fibrokeratomas are benign neoplasms that occur on fingers and toes; the classic clinical presentation is a solitary smooth nodule or dome, often with a characteristic projecting configuration and horn shape.¹ Histopathologically, these tumors are paucicellular with thick, vertically oriented, interwoven collagen bundles; cells may be positive for CD34 but are negative for EMA.^1,13 Related to acquired digital fibrokeratomas are Koenen tumors, which share a similar histology but are distinguished by their clinical characteristics. For example, Koenen tumors tend to be multifocal and are strongly associated with tuberous sclerosis. These tumors also have a tendency to recur.¹

Conclusion

Our report of 3 typical cases of SAFM highlights the need to keep this increasingly recognized and well-defined clinicopathological entity in the differential for slow-growing tumors in acral locations, particularly those in the periungual and subungual regions.

ORLANDO – In a patient presenting with a tender, firm lesion under the nail, think subungual exostosis, Dr. Phoebe Rich advised.

Subungual exostosis is a benign bony growth that can cause discomfort by pressing up from the nail bed. It can be mistaken for onychomycosis, but keep in mind that only 50% of those presenting with nail disorders will have onychomycosis, so it is important to consider other diagnoses, Dr. Rich, director of the Nail Disorder Center at Oregon Health and Science University, Portland, said at the Orlando Dermatology Aesthetic and Clinical Conference.

She described a teenager who presented with a growth under her nail, which the patient thought was nail fungus. The lesion developed after an injury experienced during a touch football game 2 months earlier.

An X-ray will aid in the diagnosis of such lesions, Dr. Rich said.

“You want to know that’s what it is … because you don’t want to just cut into it for a biopsy if you don’t know that it’s bone,” she said.

The diagnosis can be confirmed by removing the nail to take a look at the tumor.

“They are pretty characteristic. They are a bony growth. They’re actually composed of bone with a fibro-cartilaginous cap,” she said noting that tenderness is an important clue to the diagnosis.

Subungual exostosis occurs more often in toes than fingers, more often in girls than boys, and more often in children and young adults than older individuals, Dr. Rich noted.

Surgical removal is typically successful; the recurrence rate is about 10%, and recurrence is more common in children.

Presentation varies; some lesions can be quite obvious, with the growth protruding from under the nail, while others are more subtle. Dr. Rich described one young college student who presented with slight white spotting of the nail, and slight onycholysis. The patient had tenderness of the nail area when pressed, and the tumor peeked out from under the nail.

“If you see something like this, get an X-ray,” she said, adding: “You can be a hero and make the diagnosis. Don’t just treat it as though it’s a fungus.”

“If you’re very comfortable and expert at nails, great. Otherwise, make the diagnosis and send them to someone else, but you can really help these patients a lot,” she said.

Dr. Rich has participated in clinical trials with companies with antifungal/onychomycosis drugs, including Anacor, Merz, and Valeant.

ORLANDO – In a patient presenting with a tender, firm lesion under the nail, think subungual exostosis, Dr. Phoebe Rich advised.

Subungual exostosis is a benign bony growth that can cause discomfort by pressing up from the nail bed. It can be mistaken for onychomycosis, but keep in mind that only 50% of those presenting with nail disorders will have onychomycosis, so it is important to consider other diagnoses, Dr. Rich, director of the Nail Disorder Center at Oregon Health and Science University, Portland, said at the Orlando Dermatology Aesthetic and Clinical Conference.

She described a teenager who presented with a growth under her nail, which the patient thought was nail fungus. The lesion developed after an injury experienced during a touch football game 2 months earlier.

An X-ray will aid in the diagnosis of such lesions, Dr. Rich said.

“You want to know that’s what it is … because you don’t want to just cut into it for a biopsy if you don’t know that it’s bone,” she said.

The diagnosis can be confirmed by removing the nail to take a look at the tumor.

“They are pretty characteristic. They are a bony growth. They’re actually composed of bone with a fibro-cartilaginous cap,” she said noting that tenderness is an important clue to the diagnosis.

Subungual exostosis occurs more often in toes than fingers, more often in girls than boys, and more often in children and young adults than older individuals, Dr. Rich noted.

Surgical removal is typically successful; the recurrence rate is about 10%, and recurrence is more common in children.

Presentation varies; some lesions can be quite obvious, with the growth protruding from under the nail, while others are more subtle. Dr. Rich described one young college student who presented with slight white spotting of the nail, and slight onycholysis. The patient had tenderness of the nail area when pressed, and the tumor peeked out from under the nail.

“If you see something like this, get an X-ray,” she said, adding: “You can be a hero and make the diagnosis. Don’t just treat it as though it’s a fungus.”

“If you’re very comfortable and expert at nails, great. Otherwise, make the diagnosis and send them to someone else, but you can really help these patients a lot,” she said.

Dr. Rich has participated in clinical trials with companies with antifungal/onychomycosis drugs, including Anacor, Merz, and Valeant.

ORLANDO – In a patient presenting with a tender, firm lesion under the nail, think subungual exostosis, Dr. Phoebe Rich advised.

Subungual exostosis is a benign bony growth that can cause discomfort by pressing up from the nail bed. It can be mistaken for onychomycosis, but keep in mind that only 50% of those presenting with nail disorders will have onychomycosis, so it is important to consider other diagnoses, Dr. Rich, director of the Nail Disorder Center at Oregon Health and Science University, Portland, said at the Orlando Dermatology Aesthetic and Clinical Conference.

She described a teenager who presented with a growth under her nail, which the patient thought was nail fungus. The lesion developed after an injury experienced during a touch football game 2 months earlier.

An X-ray will aid in the diagnosis of such lesions, Dr. Rich said.

“You want to know that’s what it is … because you don’t want to just cut into it for a biopsy if you don’t know that it’s bone,” she said.

The diagnosis can be confirmed by removing the nail to take a look at the tumor.

“They are pretty characteristic. They are a bony growth. They’re actually composed of bone with a fibro-cartilaginous cap,” she said noting that tenderness is an important clue to the diagnosis.

Subungual exostosis occurs more often in toes than fingers, more often in girls than boys, and more often in children and young adults than older individuals, Dr. Rich noted.

Surgical removal is typically successful; the recurrence rate is about 10%, and recurrence is more common in children.

Presentation varies; some lesions can be quite obvious, with the growth protruding from under the nail, while others are more subtle. Dr. Rich described one young college student who presented with slight white spotting of the nail, and slight onycholysis. The patient had tenderness of the nail area when pressed, and the tumor peeked out from under the nail.

“If you see something like this, get an X-ray,” she said, adding: “You can be a hero and make the diagnosis. Don’t just treat it as though it’s a fungus.”

“If you’re very comfortable and expert at nails, great. Otherwise, make the diagnosis and send them to someone else, but you can really help these patients a lot,” she said.

Dr. Rich has participated in clinical trials with companies with antifungal/onychomycosis drugs, including Anacor, Merz, and Valeant.

Topical treatment of toenail onychomycosis is effective with several antifungals, Dr. Aditya Gupta of the University of Toronto and his associates reported in an evidence-based review.

The researchers identified 28 relevant studies, 13 of which were of high quality. Four antifungals were an effective cure for mild to moderate toenail onychomycosis: amorolfine, ciclopirox, tavaborole, and efinaconazole. Efinaconazole was the most effective, but in all cases, outcomes were improved with longer treatment times and follow-ups.

Oral treatments are usually more effective for toenail onychomycosis, but are not always possible because of drug interactions, so topical treatments are important in certain patient populations, the investigators noted in the article abstract.

The article abstract can be found online in the American Journal of Clinical Dermatology (doi:10.1007/s40257-014-0096-2).

Topical treatment of toenail onychomycosis is effective with several antifungals, Dr. Aditya Gupta of the University of Toronto and his associates reported in an evidence-based review.

The researchers identified 28 relevant studies, 13 of which were of high quality. Four antifungals were an effective cure for mild to moderate toenail onychomycosis: amorolfine, ciclopirox, tavaborole, and efinaconazole. Efinaconazole was the most effective, but in all cases, outcomes were improved with longer treatment times and follow-ups.

Oral treatments are usually more effective for toenail onychomycosis, but are not always possible because of drug interactions, so topical treatments are important in certain patient populations, the investigators noted in the article abstract.

The article abstract can be found online in the American Journal of Clinical Dermatology (doi:10.1007/s40257-014-0096-2).

Topical treatment of toenail onychomycosis is effective with several antifungals, Dr. Aditya Gupta of the University of Toronto and his associates reported in an evidence-based review.

The researchers identified 28 relevant studies, 13 of which were of high quality. Four antifungals were an effective cure for mild to moderate toenail onychomycosis: amorolfine, ciclopirox, tavaborole, and efinaconazole. Efinaconazole was the most effective, but in all cases, outcomes were improved with longer treatment times and follow-ups.

Oral treatments are usually more effective for toenail onychomycosis, but are not always possible because of drug interactions, so topical treatments are important in certain patient populations, the investigators noted in the article abstract.

The article abstract can be found online in the American Journal of Clinical Dermatology (doi:10.1007/s40257-014-0096-2).

Photodynamic antimicrobial chemotherapy is an effective option for treatment of in vitro onychomycosis, according to Dr. Tarun Mehra of Eberhard Karls University, Tübingen, Germany, and his associates.

In both a microdilution assay and a onychomycosis model, photodynamic antimicrobial chemotherapy (PACT) was effective in suppressing Trichophyton rubrum in conjunction with toluidine blue O (TBO) and LED irradiation. In another test, a patient diagnosed with distolateral onychomycosis was treated with TBO and PACT and experienced a significant improvement in nail health over the next 6 months while receiving no other treatments.

The long-term normalization of the patients’ nails suggests that PACT is a persistent cure, but patients with more than 50% of the nail affected may be more difficult to treat with PACT, the researchers said.

Read the full article online in the Journal of the European Academy of Dermatology and Venereology (doi:10:1111/jdv.12467).

Photodynamic antimicrobial chemotherapy is an effective option for treatment of in vitro onychomycosis, according to Dr. Tarun Mehra of Eberhard Karls University, Tübingen, Germany, and his associates.

In both a microdilution assay and a onychomycosis model, photodynamic antimicrobial chemotherapy (PACT) was effective in suppressing Trichophyton rubrum in conjunction with toluidine blue O (TBO) and LED irradiation. In another test, a patient diagnosed with distolateral onychomycosis was treated with TBO and PACT and experienced a significant improvement in nail health over the next 6 months while receiving no other treatments.

The long-term normalization of the patients’ nails suggests that PACT is a persistent cure, but patients with more than 50% of the nail affected may be more difficult to treat with PACT, the researchers said.

Read the full article online in the Journal of the European Academy of Dermatology and Venereology (doi:10:1111/jdv.12467).

Photodynamic antimicrobial chemotherapy is an effective option for treatment of in vitro onychomycosis, according to Dr. Tarun Mehra of Eberhard Karls University, Tübingen, Germany, and his associates.

In both a microdilution assay and a onychomycosis model, photodynamic antimicrobial chemotherapy (PACT) was effective in suppressing Trichophyton rubrum in conjunction with toluidine blue O (TBO) and LED irradiation. In another test, a patient diagnosed with distolateral onychomycosis was treated with TBO and PACT and experienced a significant improvement in nail health over the next 6 months while receiving no other treatments.

The long-term normalization of the patients’ nails suggests that PACT is a persistent cure, but patients with more than 50% of the nail affected may be more difficult to treat with PACT, the researchers said.

Read the full article online in the Journal of the European Academy of Dermatology and Venereology (doi:10:1111/jdv.12467).

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

Onychomycosis is a chronic fungal infection of the nails. Dermatophytes are the most common etiologic agents, but yeasts and nondermatophyte molds also constitute a substantial number of cases.¹ An accumulation of debris under distorted, deformed, thickened, and discolored nails, particularly with ragged and furrowed edges, strongly suggests tinea unguium.² Candidal onychomycosis (CO) lacks gross distortion and accumulated detritus and mainly affects fingernails.³ Nondermatophytic molds cause 1.5% to 6% of cases of onychomycosis, mostly seen in toenails of elderly individuals with a history of trauma.⁴ Onychomycosis affects 5.5% of the world population⁵ and represents 20% to 40% of all onychopathies and approximately 30% of cutaneous mycotic infections.⁶

The incidence of onychomycosis ranges from 0.5% to 5% in the general population in India.⁷ The incidence is particularly high in warm humid climates such as India.⁸ Researchers have found certain habits of the population in the Indian subcontinent (eg, walking with bare feet, wearing ill-fitting shoes, nail-biting [eg, onychophagia], working with chemicals) to be contributing factors for onychomycosis.⁹ Several studies have shown that the prevalence of onychomycosis increases with age, possibly due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, prolonged exposure to pathogenic fungi, suboptimal immune function, inactivity, or inability to trim the toenails and care for the feet.¹⁰ Nail infection is a cosmetic problem with serious physical and psychological morbidity and also serves as the fungal reservoir for skin infections. Besides destruction and disfigurement of the nail plate, onychomycosis can lead to self-consciousness and impairment of daily functioning.¹¹

Nail dystrophy occurs secondary to various systemic disorders or can be associated with other dermatologic conditions. Nail discoloration and other onychia should be differentiated from onychomycosis by classifying nail lesions as distal lateral subungual onychomycosis, proximal subungual onychomycosis (PSO), CO, white superficial onychomycosis (WSO), and total dystrophic onychomycosis.¹² Laboratory investigation is necessary to accurately differentiate between fungal infections and other skin diseases before starting treatment. Our hospital-based study sought to determine the incidence and epidemiology of onychomycosis with an analysis of 134 participants with clinically suspected onychomycosis. We evaluated prevalence based on age, sex, and occupation, as well as the most common pathogens.

Materials and Methods

Study Design and Participants

The study population consisted of 134 patients with clinically suspected onychomycosis who visited the dermatology department at the Veer Chandra Singh Garhwali Government Institute of Medical Sciences and Research Institute in Uttarakhand, India (October 2010 to October 2011). A thorough history was obtained and a detailed examination of the distorted nails was conducted in the microbiology laboratory. Patient history and demographic factors such as age, sex, occupation, and related history of risk factors for onychomycosis were recorded pro forma. Some of the details such as itching, family history of fungal infection, and prior cutaneous infections were recorded. Patients who were undergoing treatment with systemic or topical antifungal agents in the 4 weeks preceding the study period were excluded to rule out false-negative cases and to avoid the influence of antifungal agents on the disease course.

Assessments

Two samples were taken from each patient on different days. Participants were divided into 4 groups based on occupation: farmer, housewife, student, and other (eg, clerk, shopkeeper, painter). Clinical presentation of discoloration, onycholysis, subungual hyperkeratosis, and nail thickening affecting the distal and/or lateral nail plate was defined as distal lateral subungual onychomycosis; discoloration and onycholysis affecting the proximal part of the nail was defined as PSO; association with paronychia and distal and lateral onycholysis was defined as CO; white opaque patches on the nail surface were defined as WSO; and end-stage nail disease was defined as total dystrophic onychomycosis.

Prior to sampling, the nails were cleaned with a 70% alcohol solution. Nail clippings were obtained using presterilized nail clippers and a blunt no. 15 scalpel blade and were placed on sterilized black paper. Each nail sample was divided into 2 parts: one for direct microscopy and one for culture. Nail clippings were subjected to microscopic examination after clearing in 20% potassium hydroxide solution. The slides were examined for fungal hyphae, arthrospores, yeasts, and pseudohyphal forms. Culture was done with Emmons modification of Sabouraud dextrose agar (incubated at 27°C for molds and 37°C for yeasts) as well as with 0.4% chloramphenicol and 5% cycloheximide (incubated at 27°C). Culture tubes were examined daily for the first week and on alternate days thereafter for 4 weeks of incubation.

Dermatophytes were identified based on the colony morphology, growth rate, texture, border, and pigmentation in the obverse and reverse of culture media and microscopic examination using lactophenol cotton blue tease mount. Yeast colonies were identified microscopically with Gram stain, and species were identified by germ tube, carbohydrate assimilation, and fermentation tests.¹³ Nondermatophyte molds were identified by colony morphology, microscopic examination, and slide culture. Molds were considered as pathogens in the presence of the following criteria: (1) absence of other fungal growth in the same culture tube; (2) presence of mold growth in all 3 samples; and (3) presence of filaments identified on direct examination.

Results

Of 134 clinically suspected cases of onychomycosis, 78 (58.2%) were from fingernails and 56 (41.8%) from toenails. Clinical diagnosis was confirmed in 96 (71.6%) cases by both fungal culture and direct microscopy but was confirmed by direct microscopy alone in only 76 (56.7%) cases. False-negative results were found in 23.9% (32/134) of participants with direct microscopy and 9.0% (12/134) with fungal cultures. The results of direct microscopy and fungal culture are outlined in Table 1. The study included 78 (58.2%) males and 56 (41.8%) females with a mean age of 44 years. Highest prevalence (47.8%) was seen in participants older than 40 years and lowest prevalence (11.9%) in participants younger than 20 years. In total, 32.8% of participants were farmers, 31.3% were housewives, 14.9% were students, and 20.9% performed other occupations. Disease history at the time of first presentation varied from 1 month to more than 2 years; 33.6% of participants had a 1- to 6-month history of disease, while only 3.7% had a disease history of less than 1 month at presentation. The demographic data are further outlined in Table 2.

Distal lateral subungual onychomycosis was the most prevalent clinical pattern found in 66 (49.3%) participants; fungal isolates were found in 60 of these participants. The next most prevalent clinical pattern was PSO, which was found in 34 (25.4%) participants, 12 showing fungal growth. A clinical pattern of CO was noted in 28 (20.9%) participants, 22 showing fungal growth; WSO was noted in 10 (7.5%) participants, 2 showing fungal growth.

Of 96 culture-positive cases, dermatophytes were the most common pathogens isolated in 56 (58.3%) participants, followed by Candida species in 28 (29.2%) participants. Nondermatophyte molds were isolated in 12 (12.5%) participants. The various dermatophytes, Candida species, and nondermatophyte molds that were isolated on fungal culture are outlined in Table 3. Of the 96 participants with positive fungal cultures, 30 (31.2%) were farmers working with soil, 28 (29.2%) were housewives associated with wet work, 16 (16.7%) were students associated with increased physical exercise from extracurricular activity, and 22 (22.9%) were in other occupations (Table 4).

Comment

The term onychomycosis is derived from onyx, the Greek word for nail, and mykes, the Greek word for fungus. Onychomycosis is a chronic mycotic infection of the fingernails and toenails that can have a serious impact on patients’ quality of life. The fungi known to cause onychomycosis vary among geographic areas, primarily due to differences in climate.¹⁴ The isolation rate of onychomycosis in our hospital-based study was 71.6%, which is in accordance with various studies in India and abroad, including 60% in Karnataka, India⁵; 82.3% in Sikkim, India⁶; and 86.9% in Turkey.¹ However, other studies have shown lower isolation rates of 39.5% in Central Delhi, India,¹⁵ and 37.6% in Himachal Pradesh, India.¹⁶ Some patients with onychomycosis may not seek medical attention, which may explain the difference in the prevalence of onychomycosis observed worldwide.¹⁷ The prevalence of onychomycosis by age also varies. In our study, participants older than 40 years showed the highest prevalence (47.8%), which is in accordance with other studies from India¹⁸ and abroad.^19,20 In contrast, some Indian studies^15,21,22 have reported a higher prevalence in younger adults (ie, 21–30 years), which may be attributed to greater self-consciousness about nail discoloration and disfigurement as well as increased physical activity and different shoe-wearing habits. A higher prevalence in older adults, as observed in our study as well some other studies,^19,21 may be due to poor peripheral circulation, diabetes mellitus, repeated nail trauma, longer exposure to pathogenic fungi, suboptimal immune function, inactivity, and poor hygiene.¹⁰

In our study, suspected onychomycosis was more common in males (58.2%) than in females (41.8%). These results are in accordance with many of the studies in the worldwide literature.^{1,10,11,15,16,23-25} A higher isolation rate in males worldwide may be due to common use of occlusive footwear, more exposure to outdoor conditions, and increased physical activity, leading to an increased likelihood of trauma. The importance of trauma to the nails as a predisposing factor for onychomycosis is well established.²⁴ In our study, the majority of males wore shoes regardless of occupation. Perspiration of the feet when wearing socks and/or shoes can generate a warm moist environment that promotes the growth of fungi and predisposes patients to onychomycosis. Similar observations have been reported by other investigators.^21,22,25,26

The incidence of onychomycosis was almost evenly distributed among farmers, housewives, and the miscellaneous group, whereas a high isolation rate was noted among students. Of 20 students included in our study, onychomycosis was confirmed in 16, which may be related to an increased use of synthetic sports shoes and socks that retain sweat as well as vigorous physical activity frequently resulting in nail injuries among this patient population.¹¹ Younger patients may be more conscious of their appearance and therefore may be more likely to seek treatment. Similar observations have been reported by other researchers.^15,21,22

In our study, dermatophytes were the most commonly found pathogens (58.3%), which is comparable to other studies.^15,18,22Trichophyton mentagrophytes was the most frequently isolated dermatophyte from cultures, which was in concordance with a study from Delhi.¹⁵ In some studies,^18,20,22Trichophyton rubrum has been reported as the most prevalent dermatophyte, but we identified Trichophyton rubrum in only 18 participants, which can be attributed to variations in epidemiology based on geographic region. Nondermatophyte molds were isolated in 12.5% of participants, with Aspergillus niger being the most common isolate found in 8 cases. Other isolated species were Alternaria alternata and Fusarium solani found in 2 cases each. Aspergillus niger has been reported in worldwide studies as an important cause of onychomycosis.^{15,18,19,21,22}

In 28 cases (29.2%) involving Candida species, Candida albicans, Candida parapsilosis, and Candida tropicalis were the most common pathogens, respectively, which is in accordance with many studies.^15,20-22,25 In 28 cases of CO, females (n=16) were affected more than males (n=12). All of the females were housewives and C albicans was predominantly isolated from the fingernails. Household responsibilities involving kitchen work (eg, cutting and peeling vegetables, washing utensils, cleaning the house/laundry) may chronically expose housewives to moist environments and make them more prone to injury, thus facilitating easy entry of fungal agents.

Distal lateral subungual onychomycosis was the most prevalent clinical type found (n=66), which is comparable to other reports.^20,22,25 Proximal subungual onychomycosis was the second most common type; however, a greater incidence has been reported by some researchers,^23,24 while others have reported a lower incidence.^20,21 Candidial onychomycosis and WSO were not common in our study, and PSO was not associated with any immunodeficiency disease, as reported by other researchers.^15,20

Of 134 suspected cases of onychomycosis, 71.6% were confirmed by both direct microscopy and fungal culture, but only 56.7% were confirmed by direct microscopy alone. If we had relied on microscopy with potassium hydroxide only, we would have missed 23.9% of cases. Therefore, nail scrapings should always be subjected to fungal culture as well as direct microscopy, as both are necessary for accurate diagnosis and treatment of onychomycosis. If onychomycosis is not successfully treated, it can act as a reservoir of fungal infection affecting other parts of the body with the potential to pass infection on to others.

Conclusion

Clinical examination alone is not sufficient for diagnosing onychomycosis^14,18,20; in many cases of suspected onychomycosis with nail changes, mycologic examination does not confirm fungal infection. In our study, only 71.6% of participants with nail changes proved to be of fungal etiology. Other researchers from different geographic locations have reported similar results with lower incidence (eg, 39.5%,¹⁵ 37.6%,¹⁶ 51.7%,¹⁸ 45.3%²¹) of fungal etiology in such cases. Therefore, both clinical and mycologic examinations are important for establishing the diagnosis and selecting the most suitable antifungal agent, which is possible only if the underlying pathogen is correctly identified.

In summer 2014, the US Food and Drug Administration (FDA) approved 2 new topical medications for onychomycosis. In recent months, the Journal of Clinical and Aesthetic Dermatology (2014;7:10-18) and Medscape provided review materials to assist in sifting through this topic. In summary, efinaconazole, a triazole antifungal in a 10% solution recommended for daily application for 48 weeks, exhibited 17.8% complete and 55.2% mycological cure rates compared to vehicle (5.5% and 16.9%, respectively). Tavaborole, an oxaborole antifungal in a 5% solution recommended for daily application for 48 weeks, displayed 9.1% complete and 35.9% mycological cure rates versus vehicle (1.5% and 12.2%, respectively). To complete the discussion, ciclopirox nail lacquer, FDA approved in 1999 for onychomycosis for daily application for 48 weeks, heralded 8.5% complete and 36% mycological cure rates compared to vehicle (0% and 9%, respectively). Ciclopirox requires nail debridement periodically, and the newer agents do not.

What’s the issue?

Do you agree that nary a day goes by without an e-mailed article or continuing medical education opportunity tasked at “getting to know” new topical onychomycosis therapies? That being said, how often have you summarily deleted them, assuming that topicals just don’t work? I know I have, though I paused this week after thinking to myself, “How often have I written a prescription for ciclopirox nail lacquer to appease a patient who would prefer nonsystemic therapy?” And then I read on. Based on the data above, perhaps these medications, particularly efinaconazole, at least deserve perusal compared to our current meager topical and systemic options. What has your experience been with these novel topicals, their insurance coverage, and their tolerability and efficacy in your practice?

We want to know your views! Tell us what you think.

In summer 2014, the US Food and Drug Administration (FDA) approved 2 new topical medications for onychomycosis. In recent months, the Journal of Clinical and Aesthetic Dermatology (2014;7:10-18) and Medscape provided review materials to assist in sifting through this topic. In summary, efinaconazole, a triazole antifungal in a 10% solution recommended for daily application for 48 weeks, exhibited 17.8% complete and 55.2% mycological cure rates compared to vehicle (5.5% and 16.9%, respectively). Tavaborole, an oxaborole antifungal in a 5% solution recommended for daily application for 48 weeks, displayed 9.1% complete and 35.9% mycological cure rates versus vehicle (1.5% and 12.2%, respectively). To complete the discussion, ciclopirox nail lacquer, FDA approved in 1999 for onychomycosis for daily application for 48 weeks, heralded 8.5% complete and 36% mycological cure rates compared to vehicle (0% and 9%, respectively). Ciclopirox requires nail debridement periodically, and the newer agents do not.

What’s the issue?

Do you agree that nary a day goes by without an e-mailed article or continuing medical education opportunity tasked at “getting to know” new topical onychomycosis therapies? That being said, how often have you summarily deleted them, assuming that topicals just don’t work? I know I have, though I paused this week after thinking to myself, “How often have I written a prescription for ciclopirox nail lacquer to appease a patient who would prefer nonsystemic therapy?” And then I read on. Based on the data above, perhaps these medications, particularly efinaconazole, at least deserve perusal compared to our current meager topical and systemic options. What has your experience been with these novel topicals, their insurance coverage, and their tolerability and efficacy in your practice?

We want to know your views! Tell us what you think.

In summer 2014, the US Food and Drug Administration (FDA) approved 2 new topical medications for onychomycosis. In recent months, the Journal of Clinical and Aesthetic Dermatology (2014;7:10-18) and Medscape provided review materials to assist in sifting through this topic. In summary, efinaconazole, a triazole antifungal in a 10% solution recommended for daily application for 48 weeks, exhibited 17.8% complete and 55.2% mycological cure rates compared to vehicle (5.5% and 16.9%, respectively). Tavaborole, an oxaborole antifungal in a 5% solution recommended for daily application for 48 weeks, displayed 9.1% complete and 35.9% mycological cure rates versus vehicle (1.5% and 12.2%, respectively). To complete the discussion, ciclopirox nail lacquer, FDA approved in 1999 for onychomycosis for daily application for 48 weeks, heralded 8.5% complete and 36% mycological cure rates compared to vehicle (0% and 9%, respectively). Ciclopirox requires nail debridement periodically, and the newer agents do not.

What’s the issue?

Do you agree that nary a day goes by without an e-mailed article or continuing medical education opportunity tasked at “getting to know” new topical onychomycosis therapies? That being said, how often have you summarily deleted them, assuming that topicals just don’t work? I know I have, though I paused this week after thinking to myself, “How often have I written a prescription for ciclopirox nail lacquer to appease a patient who would prefer nonsystemic therapy?” And then I read on. Based on the data above, perhaps these medications, particularly efinaconazole, at least deserve perusal compared to our current meager topical and systemic options. What has your experience been with these novel topicals, their insurance coverage, and their tolerability and efficacy in your practice?

We want to know your views! Tell us what you think.

To the Editor:
Onychomycosis is a fungal infection of the nail plate by dermatophytes, yeasts, and nondermatophyte molds. It is a common problem with a prevalence of 10% to 12% in the United States.^1,2 The clinical presentation of onychomycosis is shown in the Figure. Although some patients may have mild asymptomatic cases of onychomycosis and do not inquire about treatment, many will have more advanced cases, presenting with pain and discomfort, secondary infection, unattractive appearance, or problems performing everyday functions. The goal of onychomycosis treatment is to eliminate the fungus, if possible, which usually restores the nail to its normal state when it fully grows out. Patients should be counseled that it is a long process that may take 6 months or more for fingernails and 12 to 18 months for toenails. These estimates are based on a growth rate of 2 to 3 mm per month for fingernails and 1 to 2 mm per month for toenails.³ Nails grow fastest during the teenaged years and slow down with advancing age.⁴ It should be noted that advanced cases of onychomycosis affecting the nail matrix may cause permanent scarring; therefore, the nail unit may still appear dystrophic after the causative organism is eliminated. The US Food and Drug Administration (FDA) defines a complete cure as negative potassium hydroxide preparation and negative fungal culture plus a completely normal appearance of the nail.

Treatment of onychomycosis poses a number of challenges. First, hyperkeratosis and the fungal mass may limit the delivery of topical and systemic drugs to the source of the infection. In addition, high rates of relapse and reinfection after treatment may be due to residual hyphae or spores.⁵ Furthermore, the extended length of treatment limits patient adherence and many patients are unwilling to forego wearing nail cosmetics during the course of some of the treatments.

The clinical presentation of onychomycosis. The great toenail has yellow discoloration of the nail plate, ridging, and subungual hyperkeratosis.

There are 4 approved classes of antifungal drugs for the treatment of onychomycosis: allylamines, azoles, morpholines, and hydroxypyridinones.⁶ The allylamines (eg, terbinafine) inhibit squalene epoxidase.⁷ Oral terbinafine (250 mg daily) taken for 6 weeks for fingernails and 12 weeks for toenails is considered the current systemic treatment preference in onychomycosis therapy⁸ with complete cure rates in 12-week studies of approximately 38%⁹ and 49%.¹⁰

The second class of drugs is the azoles, which inhibit lanosterol 14a-demethylase, a step in the ergosterol biosynthesis pathway.⁶ Two members of this class that are widely used in treating onychomycosis are oral itraconazole¹¹ and off-label oral fluconazole.¹² The approved dose for oral itraconazole is 200 mg daily for 3 months (or an alternative pulse regimen) with a reported complete cure rate of 14%.¹¹ Although fluconazole is not FDA approved for the treatment of onychomycosis in the United States, it is used extensively in other countries and to some extent off label in the United States. In a study of 362 patients with onychomycosis treated with oral fluconazole, complete cure rates were 48% in patients who received 450 mg weekly, 46% in those who received 300 mg weekly, and 37% in those who received 150 mg weekly for up to 9 months.¹² It should be noted that several oral triazole antifungals, namely albaconazole,¹³ posaconazole,¹⁴ and ravuconazole,¹⁵ have undergone phase 1 and 2 studies for the treatment of onychomycosis and have shown some efficacy.

Another class of antifungals are the morpholines including topical amorolfine, which is approved for use in Europe but not in North America.¹⁶ Amorolfine inhibits D14 reductase and D7-D8 isomerase, thus depleting ergosterol.¹⁷ In one randomized controlled study, the combination of amorolfine nail lacquer and oral terbinafine compared to oral terbinafine alone resulted in a higher clinical cure rate with the combination (59.2% vs 46%); complete cure rate was not reported.¹⁶

Finally, the hydroxypyridinone class includes topical ciclopirox, which has a poorly understood mechanism of action but may involve iron chelation or oxidative damage.^18,19 Ciclopirox nail lacquer 8% was approved by the FDA in 1999 and has reported complete cure rates of 5.5% to 8.5% with monthly nail debridement.²⁰

Based on the poor efficacy of many of the currently available treatments and time-consuming treatment courses, it is clear that there is a need for alternative and novel therapies. There has been a greater emphasis on topical agents due to their more favorable side-effect profile and lower risk for drug-drug interactions. Although there are many agents for the treatment of onychomycosis currently in development, many are in vitro studies or phase 1 and 2 studies. However, we will focus on drugs that are further along in phase 3 studies and those that were recently FDA approved.

Efinaconazole is a member of the azole class of drugs and has completed 2 phase 3 clinical trials (study 1, N=870; study 2, N=785).²¹ Patients in these 2 studies were randomized to receive either efinaconazole nail solution 10% or vehicle for 48 weeks followed by a 4-week washout period. Complete cure rates in the 2 studies were 17.8% and 15.2% in the treated group and 3.3% and 5.5% in the control group. The mycological cure rates were 55.2% and 53.4% in the treated group and 16.8% and 16.9% in the control group. The side-effect profile was minimal, with the most common adverse events being application-site dermatitis and vesiculation, which were not significantly higher in the treated group versus the control group.²¹ Efinaconazole received FDA approval for the treatment of toenail onychomycosis in June 2014.

There are some notable differences between ciclopirox and efinaconazole that may improve patient compliance with the latter. First, treatment with ciclopirox includes monthly nail debridement, which is not required with efinaconazole. Secondly, although ciclopirox lacquer must be removed weekly, efinaconazole is a solution, so no removal is necessary.

Terbinafine nail solution (TNS) is a member of the allylamine class and has completed phase 3 clinical trials.²² Three studies—2 vehicle controlled and 1 active comparator—were performed. The first compared TNS and vehicle, both applied daily for 24 weeks; the second study repeated the same for 48 weeks; and the third study compared TNS to amorolfine nail lacquer 5% daily for 48 weeks. The best results for complete cure were achieved with TNS for 48 weeks in the vehicle-controlled study with a rate of 2.2% versus 0%. The authors also concluded TNS was not more effective than amorolfine, as complete cure rates were 1.2% for TNS and 0.96% for amorolfine. The most common side effects were headache, nasopharyngitis, and influenza.²²

Tavaborole is a member of the new benzoxaborole class, which inhibits protein synthesis by forming an adduct with the aminoacyl–transfer RNA synthetase.²³ The topical solution was engineered to have improved penetration through the nail plate. In vitro studies showed better penetration than both ciclopirox and amorolfine.²⁴ Two identical phase 3 randomized, double-blind, vehicle-controlled studies were completed involving 1197 patients who were treated with tavaborole topical solution 5% daily compared to vehicle for 48 weeks followed by a 4-week washout period with promising results.²⁵ The incidence of treatment-related side effects was comparable to the vehicle. The most common adverse events were exfoliation, erythema, and dermatitis, all occurring at the application site.²⁵ Tavaborole was approved by the FDA for the treatment of toenail onychomycosis in July 2014.

Luliconazole is a member of the azole class and a phase 2b/3 clinical trial with a 10% solution involving 334 patients was completed in June 2013.²⁶ Results from this trial are expected in early 2015.

Lasers are a developing area for onychomycosis therapy and the appeal stems from their ability to selectively deliver energy to the target tissue, thus avoiding systemic side effects. Since 2010, the FDA has approved numerous laser devices for the temporary cosmetic improvement of onychomycosis, all of which are Nd:YAG 1064-nm lasers.^27,28 It was previously thought that the mechanism of action for the fungicidal effect was achieved with heat,²⁹ but newer in vitro studies have shown that the amount of time and level of heat required to kill Trichophyton rubrum would not be tolerable to patients.³⁰ Although the mechanism of action is poorly understood, some clinical trials have shown success using the Nd:YAG 1064-nm laser for treatment of onychomycosis. However, in a study of 8 patients treated with the Nd:YAG 1064-nm laser for 5 treatment sessions, none had a mycological or clinical cure and there was only mild clinical improvement. In addition, most patients had pain and burning during the treatments requiring many short breaks.³⁰ Although not yet FDA approved for the treatment of onychomycosis, other types of lasers are currently being studied, including CO₂, near-infrared diode, and femtosecond-infrared laser systems.³

Plasma therapy is a developing area for the treatment of onychomycosis. Plasma was shown to be fungicidal to T rubrum in an in vitro model (MOE Medical Devices, written communication, July 2012), and a clinical trial to evaluate the safety, tolerability, and efficacy of plasma in human subjects is ongoing (registered on March 22, 2013, at www.clinicaltrials.gov with the identifier NCT01819051).

Onychomycosis is a common problem that increases in prevalence with advancing age. Oral terbinafine is considered the first-line treatment at this point in time.³¹ Two new topical agents, efinaconazole and tavaborole, were recently FDA approved and may be used for the treatment of toenail onychomycosis without the need for nail debridement. The Nd:YAG laser has shown some promise in earlier clinical studies but was ineffective in a more recent study.

To the Editor:
Onychomycosis is a fungal infection of the nail plate by dermatophytes, yeasts, and nondermatophyte molds. It is a common problem with a prevalence of 10% to 12% in the United States.^1,2 The clinical presentation of onychomycosis is shown in the Figure. Although some patients may have mild asymptomatic cases of onychomycosis and do not inquire about treatment, many will have more advanced cases, presenting with pain and discomfort, secondary infection, unattractive appearance, or problems performing everyday functions. The goal of onychomycosis treatment is to eliminate the fungus, if possible, which usually restores the nail to its normal state when it fully grows out. Patients should be counseled that it is a long process that may take 6 months or more for fingernails and 12 to 18 months for toenails. These estimates are based on a growth rate of 2 to 3 mm per month for fingernails and 1 to 2 mm per month for toenails.³ Nails grow fastest during the teenaged years and slow down with advancing age.⁴ It should be noted that advanced cases of onychomycosis affecting the nail matrix may cause permanent scarring; therefore, the nail unit may still appear dystrophic after the causative organism is eliminated. The US Food and Drug Administration (FDA) defines a complete cure as negative potassium hydroxide preparation and negative fungal culture plus a completely normal appearance of the nail.

Treatment of onychomycosis poses a number of challenges. First, hyperkeratosis and the fungal mass may limit the delivery of topical and systemic drugs to the source of the infection. In addition, high rates of relapse and reinfection after treatment may be due to residual hyphae or spores.⁵ Furthermore, the extended length of treatment limits patient adherence and many patients are unwilling to forego wearing nail cosmetics during the course of some of the treatments.

The clinical presentation of onychomycosis. The great toenail has yellow discoloration of the nail plate, ridging, and subungual hyperkeratosis.

There are 4 approved classes of antifungal drugs for the treatment of onychomycosis: allylamines, azoles, morpholines, and hydroxypyridinones.⁶ The allylamines (eg, terbinafine) inhibit squalene epoxidase.⁷ Oral terbinafine (250 mg daily) taken for 6 weeks for fingernails and 12 weeks for toenails is considered the current systemic treatment preference in onychomycosis therapy⁸ with complete cure rates in 12-week studies of approximately 38%⁹ and 49%.¹⁰

The second class of drugs is the azoles, which inhibit lanosterol 14a-demethylase, a step in the ergosterol biosynthesis pathway.⁶ Two members of this class that are widely used in treating onychomycosis are oral itraconazole¹¹ and off-label oral fluconazole.¹² The approved dose for oral itraconazole is 200 mg daily for 3 months (or an alternative pulse regimen) with a reported complete cure rate of 14%.¹¹ Although fluconazole is not FDA approved for the treatment of onychomycosis in the United States, it is used extensively in other countries and to some extent off label in the United States. In a study of 362 patients with onychomycosis treated with oral fluconazole, complete cure rates were 48% in patients who received 450 mg weekly, 46% in those who received 300 mg weekly, and 37% in those who received 150 mg weekly for up to 9 months.¹² It should be noted that several oral triazole antifungals, namely albaconazole,¹³ posaconazole,¹⁴ and ravuconazole,¹⁵ have undergone phase 1 and 2 studies for the treatment of onychomycosis and have shown some efficacy.

Another class of antifungals are the morpholines including topical amorolfine, which is approved for use in Europe but not in North America.¹⁶ Amorolfine inhibits D14 reductase and D7-D8 isomerase, thus depleting ergosterol.¹⁷ In one randomized controlled study, the combination of amorolfine nail lacquer and oral terbinafine compared to oral terbinafine alone resulted in a higher clinical cure rate with the combination (59.2% vs 46%); complete cure rate was not reported.¹⁶

Finally, the hydroxypyridinone class includes topical ciclopirox, which has a poorly understood mechanism of action but may involve iron chelation or oxidative damage.^18,19 Ciclopirox nail lacquer 8% was approved by the FDA in 1999 and has reported complete cure rates of 5.5% to 8.5% with monthly nail debridement.²⁰

Based on the poor efficacy of many of the currently available treatments and time-consuming treatment courses, it is clear that there is a need for alternative and novel therapies. There has been a greater emphasis on topical agents due to their more favorable side-effect profile and lower risk for drug-drug interactions. Although there are many agents for the treatment of onychomycosis currently in development, many are in vitro studies or phase 1 and 2 studies. However, we will focus on drugs that are further along in phase 3 studies and those that were recently FDA approved.

Efinaconazole is a member of the azole class of drugs and has completed 2 phase 3 clinical trials (study 1, N=870; study 2, N=785).²¹ Patients in these 2 studies were randomized to receive either efinaconazole nail solution 10% or vehicle for 48 weeks followed by a 4-week washout period. Complete cure rates in the 2 studies were 17.8% and 15.2% in the treated group and 3.3% and 5.5% in the control group. The mycological cure rates were 55.2% and 53.4% in the treated group and 16.8% and 16.9% in the control group. The side-effect profile was minimal, with the most common adverse events being application-site dermatitis and vesiculation, which were not significantly higher in the treated group versus the control group.²¹ Efinaconazole received FDA approval for the treatment of toenail onychomycosis in June 2014.

There are some notable differences between ciclopirox and efinaconazole that may improve patient compliance with the latter. First, treatment with ciclopirox includes monthly nail debridement, which is not required with efinaconazole. Secondly, although ciclopirox lacquer must be removed weekly, efinaconazole is a solution, so no removal is necessary.

Terbinafine nail solution (TNS) is a member of the allylamine class and has completed phase 3 clinical trials.²² Three studies—2 vehicle controlled and 1 active comparator—were performed. The first compared TNS and vehicle, both applied daily for 24 weeks; the second study repeated the same for 48 weeks; and the third study compared TNS to amorolfine nail lacquer 5% daily for 48 weeks. The best results for complete cure were achieved with TNS for 48 weeks in the vehicle-controlled study with a rate of 2.2% versus 0%. The authors also concluded TNS was not more effective than amorolfine, as complete cure rates were 1.2% for TNS and 0.96% for amorolfine. The most common side effects were headache, nasopharyngitis, and influenza.²²

Tavaborole is a member of the new benzoxaborole class, which inhibits protein synthesis by forming an adduct with the aminoacyl–transfer RNA synthetase.²³ The topical solution was engineered to have improved penetration through the nail plate. In vitro studies showed better penetration than both ciclopirox and amorolfine.²⁴ Two identical phase 3 randomized, double-blind, vehicle-controlled studies were completed involving 1197 patients who were treated with tavaborole topical solution 5% daily compared to vehicle for 48 weeks followed by a 4-week washout period with promising results.²⁵ The incidence of treatment-related side effects was comparable to the vehicle. The most common adverse events were exfoliation, erythema, and dermatitis, all occurring at the application site.²⁵ Tavaborole was approved by the FDA for the treatment of toenail onychomycosis in July 2014.

Luliconazole is a member of the azole class and a phase 2b/3 clinical trial with a 10% solution involving 334 patients was completed in June 2013.²⁶ Results from this trial are expected in early 2015.

Lasers are a developing area for onychomycosis therapy and the appeal stems from their ability to selectively deliver energy to the target tissue, thus avoiding systemic side effects. Since 2010, the FDA has approved numerous laser devices for the temporary cosmetic improvement of onychomycosis, all of which are Nd:YAG 1064-nm lasers.^27,28 It was previously thought that the mechanism of action for the fungicidal effect was achieved with heat,²⁹ but newer in vitro studies have shown that the amount of time and level of heat required to kill Trichophyton rubrum would not be tolerable to patients.³⁰ Although the mechanism of action is poorly understood, some clinical trials have shown success using the Nd:YAG 1064-nm laser for treatment of onychomycosis. However, in a study of 8 patients treated with the Nd:YAG 1064-nm laser for 5 treatment sessions, none had a mycological or clinical cure and there was only mild clinical improvement. In addition, most patients had pain and burning during the treatments requiring many short breaks.³⁰ Although not yet FDA approved for the treatment of onychomycosis, other types of lasers are currently being studied, including CO₂, near-infrared diode, and femtosecond-infrared laser systems.³

Plasma therapy is a developing area for the treatment of onychomycosis. Plasma was shown to be fungicidal to T rubrum in an in vitro model (MOE Medical Devices, written communication, July 2012), and a clinical trial to evaluate the safety, tolerability, and efficacy of plasma in human subjects is ongoing (registered on March 22, 2013, at www.clinicaltrials.gov with the identifier NCT01819051).

Onychomycosis is a common problem that increases in prevalence with advancing age. Oral terbinafine is considered the first-line treatment at this point in time.³¹ Two new topical agents, efinaconazole and tavaborole, were recently FDA approved and may be used for the treatment of toenail onychomycosis without the need for nail debridement. The Nd:YAG laser has shown some promise in earlier clinical studies but was ineffective in a more recent study.

To the Editor:
Onychomycosis is a fungal infection of the nail plate by dermatophytes, yeasts, and nondermatophyte molds. It is a common problem with a prevalence of 10% to 12% in the United States.^1,2 The clinical presentation of onychomycosis is shown in the Figure. Although some patients may have mild asymptomatic cases of onychomycosis and do not inquire about treatment, many will have more advanced cases, presenting with pain and discomfort, secondary infection, unattractive appearance, or problems performing everyday functions. The goal of onychomycosis treatment is to eliminate the fungus, if possible, which usually restores the nail to its normal state when it fully grows out. Patients should be counseled that it is a long process that may take 6 months or more for fingernails and 12 to 18 months for toenails. These estimates are based on a growth rate of 2 to 3 mm per month for fingernails and 1 to 2 mm per month for toenails.³ Nails grow fastest during the teenaged years and slow down with advancing age.⁴ It should be noted that advanced cases of onychomycosis affecting the nail matrix may cause permanent scarring; therefore, the nail unit may still appear dystrophic after the causative organism is eliminated. The US Food and Drug Administration (FDA) defines a complete cure as negative potassium hydroxide preparation and negative fungal culture plus a completely normal appearance of the nail.

Treatment of onychomycosis poses a number of challenges. First, hyperkeratosis and the fungal mass may limit the delivery of topical and systemic drugs to the source of the infection. In addition, high rates of relapse and reinfection after treatment may be due to residual hyphae or spores.⁵ Furthermore, the extended length of treatment limits patient adherence and many patients are unwilling to forego wearing nail cosmetics during the course of some of the treatments.

The clinical presentation of onychomycosis. The great toenail has yellow discoloration of the nail plate, ridging, and subungual hyperkeratosis.

There are 4 approved classes of antifungal drugs for the treatment of onychomycosis: allylamines, azoles, morpholines, and hydroxypyridinones.⁶ The allylamines (eg, terbinafine) inhibit squalene epoxidase.⁷ Oral terbinafine (250 mg daily) taken for 6 weeks for fingernails and 12 weeks for toenails is considered the current systemic treatment preference in onychomycosis therapy⁸ with complete cure rates in 12-week studies of approximately 38%⁹ and 49%.¹⁰

The second class of drugs is the azoles, which inhibit lanosterol 14a-demethylase, a step in the ergosterol biosynthesis pathway.⁶ Two members of this class that are widely used in treating onychomycosis are oral itraconazole¹¹ and off-label oral fluconazole.¹² The approved dose for oral itraconazole is 200 mg daily for 3 months (or an alternative pulse regimen) with a reported complete cure rate of 14%.¹¹ Although fluconazole is not FDA approved for the treatment of onychomycosis in the United States, it is used extensively in other countries and to some extent off label in the United States. In a study of 362 patients with onychomycosis treated with oral fluconazole, complete cure rates were 48% in patients who received 450 mg weekly, 46% in those who received 300 mg weekly, and 37% in those who received 150 mg weekly for up to 9 months.¹² It should be noted that several oral triazole antifungals, namely albaconazole,¹³ posaconazole,¹⁴ and ravuconazole,¹⁵ have undergone phase 1 and 2 studies for the treatment of onychomycosis and have shown some efficacy.

Another class of antifungals are the morpholines including topical amorolfine, which is approved for use in Europe but not in North America.¹⁶ Amorolfine inhibits D14 reductase and D7-D8 isomerase, thus depleting ergosterol.¹⁷ In one randomized controlled study, the combination of amorolfine nail lacquer and oral terbinafine compared to oral terbinafine alone resulted in a higher clinical cure rate with the combination (59.2% vs 46%); complete cure rate was not reported.¹⁶

Finally, the hydroxypyridinone class includes topical ciclopirox, which has a poorly understood mechanism of action but may involve iron chelation or oxidative damage.^18,19 Ciclopirox nail lacquer 8% was approved by the FDA in 1999 and has reported complete cure rates of 5.5% to 8.5% with monthly nail debridement.²⁰

Based on the poor efficacy of many of the currently available treatments and time-consuming treatment courses, it is clear that there is a need for alternative and novel therapies. There has been a greater emphasis on topical agents due to their more favorable side-effect profile and lower risk for drug-drug interactions. Although there are many agents for the treatment of onychomycosis currently in development, many are in vitro studies or phase 1 and 2 studies. However, we will focus on drugs that are further along in phase 3 studies and those that were recently FDA approved.

Efinaconazole is a member of the azole class of drugs and has completed 2 phase 3 clinical trials (study 1, N=870; study 2, N=785).²¹ Patients in these 2 studies were randomized to receive either efinaconazole nail solution 10% or vehicle for 48 weeks followed by a 4-week washout period. Complete cure rates in the 2 studies were 17.8% and 15.2% in the treated group and 3.3% and 5.5% in the control group. The mycological cure rates were 55.2% and 53.4% in the treated group and 16.8% and 16.9% in the control group. The side-effect profile was minimal, with the most common adverse events being application-site dermatitis and vesiculation, which were not significantly higher in the treated group versus the control group.²¹ Efinaconazole received FDA approval for the treatment of toenail onychomycosis in June 2014.

There are some notable differences between ciclopirox and efinaconazole that may improve patient compliance with the latter. First, treatment with ciclopirox includes monthly nail debridement, which is not required with efinaconazole. Secondly, although ciclopirox lacquer must be removed weekly, efinaconazole is a solution, so no removal is necessary.

Terbinafine nail solution (TNS) is a member of the allylamine class and has completed phase 3 clinical trials.²² Three studies—2 vehicle controlled and 1 active comparator—were performed. The first compared TNS and vehicle, both applied daily for 24 weeks; the second study repeated the same for 48 weeks; and the third study compared TNS to amorolfine nail lacquer 5% daily for 48 weeks. The best results for complete cure were achieved with TNS for 48 weeks in the vehicle-controlled study with a rate of 2.2% versus 0%. The authors also concluded TNS was not more effective than amorolfine, as complete cure rates were 1.2% for TNS and 0.96% for amorolfine. The most common side effects were headache, nasopharyngitis, and influenza.²²

Tavaborole is a member of the new benzoxaborole class, which inhibits protein synthesis by forming an adduct with the aminoacyl–transfer RNA synthetase.²³ The topical solution was engineered to have improved penetration through the nail plate. In vitro studies showed better penetration than both ciclopirox and amorolfine.²⁴ Two identical phase 3 randomized, double-blind, vehicle-controlled studies were completed involving 1197 patients who were treated with tavaborole topical solution 5% daily compared to vehicle for 48 weeks followed by a 4-week washout period with promising results.²⁵ The incidence of treatment-related side effects was comparable to the vehicle. The most common adverse events were exfoliation, erythema, and dermatitis, all occurring at the application site.²⁵ Tavaborole was approved by the FDA for the treatment of toenail onychomycosis in July 2014.

Luliconazole is a member of the azole class and a phase 2b/3 clinical trial with a 10% solution involving 334 patients was completed in June 2013.²⁶ Results from this trial are expected in early 2015.

Lasers are a developing area for onychomycosis therapy and the appeal stems from their ability to selectively deliver energy to the target tissue, thus avoiding systemic side effects. Since 2010, the FDA has approved numerous laser devices for the temporary cosmetic improvement of onychomycosis, all of which are Nd:YAG 1064-nm lasers.^27,28 It was previously thought that the mechanism of action for the fungicidal effect was achieved with heat,²⁹ but newer in vitro studies have shown that the amount of time and level of heat required to kill Trichophyton rubrum would not be tolerable to patients.³⁰ Although the mechanism of action is poorly understood, some clinical trials have shown success using the Nd:YAG 1064-nm laser for treatment of onychomycosis. However, in a study of 8 patients treated with the Nd:YAG 1064-nm laser for 5 treatment sessions, none had a mycological or clinical cure and there was only mild clinical improvement. In addition, most patients had pain and burning during the treatments requiring many short breaks.³⁰ Although not yet FDA approved for the treatment of onychomycosis, other types of lasers are currently being studied, including CO₂, near-infrared diode, and femtosecond-infrared laser systems.³

Plasma therapy is a developing area for the treatment of onychomycosis. Plasma was shown to be fungicidal to T rubrum in an in vitro model (MOE Medical Devices, written communication, July 2012), and a clinical trial to evaluate the safety, tolerability, and efficacy of plasma in human subjects is ongoing (registered on March 22, 2013, at www.clinicaltrials.gov with the identifier NCT01819051).

Onychomycosis is a common problem that increases in prevalence with advancing age. Oral terbinafine is considered the first-line treatment at this point in time.³¹ Two new topical agents, efinaconazole and tavaborole, were recently FDA approved and may be used for the treatment of toenail onychomycosis without the need for nail debridement. The Nd:YAG laser has shown some promise in earlier clinical studies but was ineffective in a more recent study.