ADVERTISEMENT
Keys To Diagnosing And Treating Dystrophic Toenails
Abnormal toenails are a common concern among podiatric patients. In a thorough review of the literature on dystrophic toenails, this author emphasizes key principles in the diagnostic workup, pertinent clinical signs to aid in the differential diagnosis and when clinicians should have an elevated index of suspicion for malignant processes.
Evaluation and management of dystrophic nails can be challenging at times. Any prolonged history, especially of single nail dystrophy, should raise one’s index of suspicion.1 While it is true that fungus and trauma are common causes of dystrophic nails, more serious diagnoses also exist, and clinicians must not be complacent in the evaluation.
I personally define a dystrophic toenail as any nail which is not a normal, translucent, flat nail. Haneke defines nail dystrophy as temporary or permanent damage of the nail plate and/or other visible structures of the nail organ.2 To a podiatrist, dystrophy suggests a thick nail as it pertains to ICD-10 code L60.3 and CPT code G0127 (trimming of dystrophic nail). In truth, it is anything and everything encompassing chronic nail malformation.3
Dystrophic symptoms can exist simultaneously and any change in the toenail can impair foot function. Additionally, aesthetics may impact self-esteem and interaction with others.4 Though often associated with thickness, the complete description of nail dystrophy can include fragility, lysis, splinter hemorrhage, subungual hematoma, splitting, onychomadesis, onychogryphosis, subungual keratosis, ridging, pitting, thinning and nail plate pigmentation. We can also use terms such as trachyonychia or 20-nail dystrophy, as described by Sehgel.5 This phenomenon is caused by disruption of the nail matrix and clinicians use the term to describe sandpaper-like roughness and pitting.5
Essential Keys To The Diagnostic Workup For Patients With Dystrophic Nails
There are multiple important pieces of information to obtain in the patient history. Is there a history of trauma (such as sports injuries) to the toe? Is there an associated dermatologic history? Has the patient had foot, toe or nail surgery? Has he or she had a nail bed or matrix biopsy, skin lesion or wart excision? Does the patient have a history of cancer? If so, what type? What medications or treatments has the patient used? Has the patient had IV medication infusion, antimalarial drug therapy or recent antibiotic therapy?
Single nail involvement may be a marker for melanoma so clinicians should always investigate chronic unexplained monodactylic nail dystrophy histologically.6 It is also prudent to examine the fingernails and palms to see if there is any additional involvement. Evaluate for any deformity that may affect the toenails. Multiple biomechanical conditions can cause microtrauma and nail dystrophy. Review actual and perceived shoe sizing and style. One must consider toe box height, size and width as potential sources of microtrauma.
Nail samples: KOH, PAS, PCR. To rule in onychomycosis, histological examination of nail clippings with periodic acid-Schiff (PAS) staining is most sensitive. If positive, this test will identify certain polysaccharides present in the walls of fungal elements. Nagar and colleagues instead used subungual hyperkeratosis samples that contained more fungal elements than the nail plate itself.7
Culture. Although it may identify an exact bacterial or fungal organism, culture alone has a low sensitivity for dermatophytes with up to 60 percent false negative results.7
Biopsy. In cases of isolated nail psoriasis, isolated nail lichen planus, onychomycosis not confirmed on direct microscopy and culture, or longitudinal melanonychia, biopsy may become necessary. When it comes to nails, it is best to reserve biopsy for clinically ambiguous nail conditions that one cannot diagnose by history, clinical appearance and routine mycology.8
Nail plate biopsy gives limited histopathologic data but is useful in suspected cases of onychomycosis, warts and nail psoriasis. One would use nail bed biopsy for onycholysis or subungual hyperkeratosis, cases of nail bed discoloration or painful nail bed lesions. Nail matrix biopsy is best to differentiate longitudinal pigmented bands, benign lesions of the nail matrix, malignant lesions or acquired nail plate defects.8
Avulsion. Nail avulsion can be a diagnostic method to examine subungual structures for example. It can also be a treatment for dystrophic toenails.
Dermoscopy. A dermatoscope is an important adjunctive tool. Clinicians widely use this modality for the diagnosis of melanocytic and non-melanocytic lesions, inflammatory and infectious conditions. One needs to understand the onychoscopic and capillaroscopic parameters of a normal nail before he or she can appreciate disease-induced changes. Benign proliferations produce parallel, regularly patterned and spaced, brown-black bands of uniform color and thickness. Malignancy is suggested by irregular patterns and spacing, varying coloration and crossing bands of varying thickness.9 Melanoma specifically exhibits a pigmented band more than 2/3 the width of the nail plate, irregular grey and black coloration, Hutchinson’s and Micro-Hutchinson’s signs, and nail dystrophy.9
Onychomycosis also has distinct features dermatoscopically, including a spiked pattern, longitudinal striae, linear edges and distal irregular termination. This is helpful as PAS, PCR and cultures are not always accurate and may be cost-prohibitive.10
Onychoscopy helps clearly delineate the presence of splinter hemorrhages and can show dilated capillaries that one sees with connective tissue disorders. It is helpful in distinguishing subungual hematoma from melanoma. Recent hematoma tends to be deeper and more irregular than older hematomas. Hemorrhage grows out with the growth of nail plate. However, failure to migrate should raise suspicion for subungual melanoma.9
X-ray. Radiographs can rule out subungual exostosis and evaluate for possible erosion of bone in advanced tumor cases. A single dystrophic nail is a clear indication for X-ray.
MRI. High-resolution MRI allows accurate detection and mapping of nail lesions, more detailed assessment of phalangeal soft tissues and can suggest a specific diagnosis. There is now a protocol for the workup of nail tumors that one can see on MRI.11 A small sampling of tumors clinicians can see on MRI include glomus tumor, onychomatricoma, hemangioma, subungual melanoma, subungual squamous cell carcinoma and tumor mimics such as mucoid cysts and epidermoid cysts.
Additional testing. When a nail inadequately responds to antifungal medication or nail dystrophy persists or changes, even with a confirmed diagnosis of onychomycosis, it may warrant repeat evaluation including a biopsy to exclude possibility of a subungual tumor.
Recognizing The Characteristics Of Dystrophic Toenails
Onycholysis. Onycholysis is the separation of the nail plate from the nail bed due to disruption of the onychocorneal band, starting at the distal free margin. Less often, the separation begins at the proximal edge. This is known as onychomadesis and one sees this most notably in patients with psoriasis.
Onycholysis is very common but rarely associated with inflammation. The lifted area is usually smooth and white because of the presence of air under the detached nail plate.12 It may occasionally show a green or brown discoloration caused by colonization by chromogenic bacteria (Pseudomonas aeruginosa) and fungi. Chronic onycholysis leads to keratinization of the nail bed and may cause a disappearing nail bed, or when the nail plate is shortened by more than 20 percent in comparison to an unaffected contralateral toe.13 If onycholysis is left untreated, it may lead to nail bed scarring.
The primary causes of onycholysis include contact irritants, trauma, moisture, systemic diseases, dermatologic diseases, infections and various drugs. Certain drugs, such as tetracyclines, psoralens, NSAIDs and quinolones, can cause a phototoxicity reaction, which results in onycholysis.13
Treatment involves removal of the onycholytic portion of the nail with subsequent application of topical tretinoin to the nail bed. In one study, Dias and coworkers used daily tretinoin 0.025% gel, which resulted in complete improvement of the condition at a three-month follow-up.14 Retinoids have the potential to delay epithelial keratinization and increase the expression of intercellular adhesion molecules (e.g. desmosomes), which may promote adhesion of the nail plate to the nail bed. In another study, Iorizzo and colleagues recommended application of a topical antiseptic solution (2% to 4% thymol in chloroform twice daily) on the exposed nail bed and sodium hypochlorite solution, one drop twice daily around the nail, to remove P. aeruginosa when present.12
Thick nails. Onychogryphosis refers to nail plate thickening with gross hyperkeratosis and increased curvature of the nail plate, either downward (oyster-like) or upward (ram’s horn). Onychauxis is a thickened nail plate in general without deformity or change in the curvature of the nail plate.15
Brittle nails. Associated with an intrinsic defect in the intercellular cement that holds together nail plate keratinocytes, brittle nails exhibit disorganization of protein structure, lipid structure and orientation of keratin filaments. Normal nail plate contains up to 10 percent sulfur by weight, 18 percent water and less than five percent lipids. Nails become brittle when the water content is less than 16 percent and become soft when it is above 25 percent.16,17
Aging and environmental factors that dehydrate the nail plate (shoe trauma, overaggressive manicuring) also play important roles in the development of nail brittleness. Nail fragility manifests with several nail plate abnormalities, such as onychoschizia and onychorrhexis. Oral supplementation with vitamins (especially biotin), oligoelements and amino acids (especially cysteine) can be useful in improving nail strength.
Nail moisturizers are important in patients with brittle nails due to occlusives and humectants.12 Clinicians may also add alpha-hydroxy acids and urea to increase the water-binding capacity of the nail plate. There are lacquers, including 16% poly-ureaurethane (Nuvail™, EPI Health) and hydroxypropyl chitosan (Genadur®, Medimetriks), that specifically restructure nails affected by dystrophy and fragilty.12
Discoloration. Pigmentation of the nail plate can be due to bacteria, fungi, melanin or blood. Demonstration of blood does not rule out a carcinoma or tumor because advanced malignancies may ulcerate and bleed.
Melanonychia is typically benign and is defined as brown or black pigmentation involving the nail plate due to the presence of melanin. The older the patient is at the onset of melanonychia, the more suspicious the lesion. Although rare, melanonychia may be the initial presentation of melanoma.18 Accordingly, all cases require in-depth examination.
The deposition of melanin results from melanocytic activation, melanocytic hyperplasia and external sources such as pathogens (gram negative bacteria, dermatophytes). Melanocytic activation has multiple causes. Racial variation increases with age. Pregnancy, trauma and endocrine disorders are all contributing factors. Inflammatory conditions also play a role as does onychomycosis, which can be both infectious and inflammatory. Nonmelanocytic conditions such as basal cell carcinoma may cause melanocytic activation. Melanocytic hyperplasia is when there are increased melanocytes in the nail matrix. This can be either benign or malignant and shows grey to brown pigmented nail bands.19 Pigmentation can also be caused by medications including chemotherapy agents and antibiotics. One case study specifically cites sparfloxacin, a quinolone, as a potential cause.20
A study by Alani and colleagues showed a wide range of diagnoses for pigmented nail presentations. Of 38 patients with nail pigmentation, retrospective analysis revealed diagnoses including fungating amelanotic melanoma, subungual hematoma, viral wart, acral fibrokeratoma, myxoid cyst, fungal nail, Pseudomonas infection, benign linear pigmentation, Bowen’s disease, psoriasis and matrix malalignment.21
A Closer Look At Systemic And Dermatologic Causes Of Onychodystrophy
Systemic disease. When considering systemic diseases, fingernails usually provide more accurate information than toenails, which are often modified by trauma.22 Momen and Al-Niaimi provide a good review of the exhaustive list of different systemic diseases associated with nail changes.23
Psoriasis. This condition presents with irregular pitting, surface ridging and nail plate thickening when psoriasis is of the nail matrix. In the nail bed, salmon patches, onycholysis with erythematous borders, splinter hemorrhages and subungual hyperkeratosis are more indicative. All these signs can present together in the same patient and even in the same nail.12 Clinicians can confuse psoriatic toenails with mycotic toenails and both can coexist.
Treatment is not always helpful. Classically, the first line of treatment for nail psoriasis has been topical medication such as calcipotriol and betamethasone dipropionate, or topical tazarotene 0.1%, especially for nail bed psoriasis.23 Clinicians use high-potency steroids more for nail matrix involvement. One common treatment for a limited number of affected nails is triamcinolone acetonide 10 mg/mL (maximum 4 injections of 0.1 mL per digit), which one injects into the proximal nail fold (in patients with nail matrix psoriasis) or the lateral nail folds (in patients with nail bed psoriasis). One should repeat these injections monthly for six months, then every six weeks for the next six months and then every two months for six to 12 months.24
When all 10 toenails are affected, systemic treatment, including methotrexate and systemic corticosteroids, is favored. Biologic agents have enriched the therapeutic armamentarium against psoriatic nails but are generally restricted to patients with a concomitant skin and/or joint psoriasis because of their high cost and toxicity. Tofacitinib (Xeljanz®, Pfizer) appears to be beneficial for psoriatic nails refractory to other modes of therapy.26
Lichen planus. Lichen planus is a chronic autoimmune disorder that typically develops in middle-aged adults. It is an idiopathic inflammatory dermatitis involving skin, mucous membranes, hair and nails. Lichen planus is self-limiting and promptly regresses with treatment. Recurrences of nail lesions as well as development of lesions in other regions of the body are possible. If this condition is not detected early, it can destroy the nail plate. A small subset of patients develop severe and early nail matrix destruction.27
The nail plate may be greatly thinned and, at times, distinct papules may involve the nail bed. Twenty-nail dystrophy may be the sole manifestation of lichen planus. Other nail changes include irregular longitudinal grooving and ridging, pterygium formation, shedding of the nail plate with atrophy of the nail bed, subungual keratosis, onychopapilloma, erythronychia (red streaks), subungual hyperpigmentation and nail degloving. Biopsy is needed for diagnosis.
Sarcoidosis. Nail involvement in sarcoidosis is rare but its presence is often associated with chronic systemic disease. It can include dystrophy, onycholysis and subungual or nail hyperkeratosis. In almost half of cases, one will note bony cysts on radiological examination.22 The presence of nail dystrophy in a patient with sarcoidosis should therefore prompt radiological examination and investigation for systemic involvement.
Peripheral arterial disease. Onychodystrophy may also be an early marker of asymptomatic peripheral arterial disease (PAD). Accordingly, Moreno-Coutino and coworkers recommend an ABI for all elderly patients with onychodystrophy.28
Analyzing The Impact Of Aging, Cancer Treatment And Trauma
Age-related dystrophy. Nail dystrophy is prevalent with aging.29 Elderly people with diabetes should be treated for onychomycosis to prevent secondary bacterial infections and subsequent complications. However, they are at increased risk for poor response to treatment.30 Age-associated disorders include brittle nails, trachyonychia, onychauxis, pachyonychia, onychogryphosis, onychophosis, onychoclavus, onychocryptosis, onycholysis, infections, infestations, splinter hemorrhages, subungual hematoma, subungual exostosis and malignancies. With aging, the rate of growth, color, contour, surface, thickness, chemical composition and histology of the nail unit change. Onychorrhexis (increased longitudinal striations) may also appear, as can Beau’s lines (transverse ridges) and trachyonychia.16
Secondary to anti-cancer medication. Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events. Onycholysis, brittle nails and slower nail growth can occur. Close collaboration between podiatrists and oncologists is essential.31
Many chemotherapeutic agents cause mucocutaneous toxicity. In one report of two cases, temsirolimus (Torisel®, Pfizer) was associated with 20-nail dystrophy including fragility, distal onycholysis, yellow discoloration and painful paronychia.32 Red-brown discoloration of the nail plate, onycholysis with leukonychia, proximal subungual hemorrhage and subungual or periungual pyogenic granuloma are also possible.
Taxanes (docetaxel and paclitaxel) are antitumor drugs used in the management of breast cancer as well as other solid tumors and are associated with nail toxicity.33,34 If an impaired physical barrier such as onycholysis exists, bacterial infections become common with dystrophy of the nail. This is secondary to the anti-mitotic effect of taxanes in the nail matrix and suppression of the immune response.35
Nail trauma. The most common nail disorders are linked to repeated trauma.As most podiatrists know, nail trauma can be secondary to a bony deformity as well as inadequate shoe gear. It can be a single traumatic event or it can be from decades of microtrauma. Other causes include habitual picking of the proximal nail fold and post-surgical changes.3
Nail trauma may also be due to a subungual exostosis, a relatively common benign bone tumor that occurs in the distal phalanges and can be a source of pain and nail deformity.
Trauma can also cause a pyogenic granuloma. Nail pyogenic granuloma can also be due to drugs or peripheral nerve injury. Location, the number of digits involved and clinical history help to identify the cause. When there is a single granuloma, especially one that involves the nail bed, histological examination is prudent to rule out malignant melanoma.
Trauma due to a short shoe or hammertoe can cause retronychia or proximal non-infectious paronychia. It results in thickening of the nail plate from a halt in nail growth. Avulsion resolves the symptoms and allows one to see under the nail plate. Avulsion allows for biopsy as well.36
Addressing Neoplastic Considerations With Onychodystrophy
Nail dystrophy not responding to treatment needs careful examination, including biopsy, to rule out tumors.2 Nail neoplasms include all tumors occurring in the nail or periungual tissue, and can be benign or malignant. Early malignant tumors, like melanoma and squamous cell carcinoma, can present similarly to onychomycosis or benign melanonychia. Therefore, these tumors are frequently missed by clinicians.37
In recent years, researchers have described and classified a number of nail-specific tumors based on origin.2 Onychomatricoma, onychocytic carcinoma and onychopapilloma originate from the nail matrix. Onycholemmal cysts, onycholemmal horn and the proliferating onycholemmal tumor are characteristic nail bed tumors.2
Bowen’s disease. Otherwise known as squamous cell carcinoma in situ, Bowen’s disease is the most common malignant nail tumor. It presents as a flat, verrucous lesion on the lateral or distal aspect of the nail. Bowen’s disease can also manifest as an erythematous patch or flat plaque with textural changes of the nail plate, loss of transparency and sheen, an isolated red streak in the nail bed or onycholysis.
Basal cell carcinoma. The most common malignancy in humans, this rarely occurs on the nail unit and may be frequently misdiagnosed clinically. When it does occur, it most commonly presents as ulceration.38
Squamous cell carcinoma. Diagnosis of this tumor is often delayed due to likeness to benign or infectious processes. Valero and colleagues note this presentation is due to chronic tissue irritation associated with subungual exostosis.39 While it is rare in the ungual apparatus, there are two subtypes. The first develops mainly near the nail fold with a hyperkeratotic warty appearance and evidence of thrombosed capillaries. The other subtype starts in the nail bed and develops mostly as a mass that may dislocate the nail plate, leading to nodular, ulcerated lesions that invade the underlying tissue and bone.40
Nail unit melanoma. A variant of acral lentiginous melanoma, nail unit melanoma is often an incidental diagnosis. Early diagnosis at the in situ stage is difficult but essential to improve prognosis.41 Longitudinal melanonychia may not be the patient’s presenting concern. While longitudinal melanonychia is not a specific sign for melanoma, one must evaluate it and, at times, seek a biopsy. Many times, the melanonychia presents as single or multiple melanotic macules smaller than one cm in diameter, usually brown with sharp edges.42
In one study over a 13-year period, Neczyporenko and colleagues found that monodactylic longitudinal melanonychia was the most frequent presentation of nail unit melanoma and the mean diagnosis delay was five years.41 Suspicion was based on clinical and dermatoscopic signs, and was confirmed by pathological examination.41 Unlike skin dermoscopy, nail unit dermoscopy evaluates the sites of melanin deposition rather than the underlying patterns in the nail matrix.
Baran and Kechijian note clinical clues for identification of melanoma including de novo single-digit lesions in older patients, abrupt appearance of lesions, blurred or irregular borders, sudden changes in color, development of a Hutchinson’s sign, and past history of melanoma.43 Longitudinal melanonychia with Caucasian skin mandates consideration of melanoma in situ and the threshold for biopsy should be low.1
Additional pertinent considerations in evaluation include a personal or family history of melanoma, rapid growth of the dystrophy, melanonychial band darkening or width of >3 mm, pigment variegation, blurry lateral borders, irregular nail surface elevation or proximal widening.44
The high mortality reported in the literature is most likely due to advanced disease associated with delayed diagnosis and treatment. In one study by Lee and colleagues, in situ melanoma showed longitudinal streaks with no nail dystrophy while invasive melanoma presented with dystrophy such as longitudinal splitting.45 There is a window of time in which to make a diagnosis. Awareness of early signs of nail melanoma is vital since prognosis depends on early treatment.
Amelanotic melanoma. Representing 20-33 percent of all nail melanomas, amelanotic melanoma can present as persistent nail plate dystrophy and masquerade as onychomycosis. In one study, two patients had a concurrent biopsy/culture that confirmed the presence of fungal elements.46 The dystrophy did not resolve and both patients later presented with non-pigmented nodules with subsequent biopsies revealing melanoma. Hence, the diagnosis of onychomycosis does not exclude the possibility of amelanotic melanoma in a patient with persistent nail dystrophy.
Onychomatricoma. Pigmented onychomatricoma is a rare mimic of subungual melanoma deriving from the nail matrix and growing within the nail plate.47 Onychomatricoma mimics squamous cell carcinoma and usually presents a thickened nail with xanthonychia (yellow nail plate band), increased transverse curvature, proximal splinter hemorrhages (due to vascular stroma) and swelling of the proximal nail fold.48 Bleeding during nail trimming is a common feature. Since the differential diagnosis includes carcinoma, nail avulsion and biopsy are necessary, especially if fungal culture and X-ray are normal. In this case, the mass would extrude from below the proximal nail fold toward the distal end of the nail bed. As with melanoma, the index of suspicion for onychomatricoma should increase with presence of a singular dystrophic nail.49
Other common nail tumors. Characteristics of onychopapilloma may include erythronychia, splinter hemorrhages, a longitudinal marked ridge of the nail bed, subungual keratosis and associated localized onycholysis. Glomus tumors exhibit a painful blue/red subungual macule and require X-rays as they may cause bony erosion.50
Treatment Of Nail Tumors: What You Should Know
Clinicians may refer patients for Mohs micrographic surgery in cases in which tissue conservation is crucial, such as in the nail unit. It allows for control of margins and functional preservation. Mohs surgeons presently use this surgery to treat multiple malignant and benign neoplasms. Other treatments include wide excision of the nail unit with subsequent use of a full-thickness skin graft for squamous cell carcinoma without bone involvement. Digital amputation is another form of treatment.50 Treatment of non-invasive melanoma is functional excision of the tumor with a safety margin but without bone resection.41 Therefore, amputations in subungual melanoma are no longer recommended. Advanced cases involving bone and joint spaces may not be suitable for functional surgery and warrant amputation.41
Examining Infectious Etiologies Of Onychodystrophy
Onychomycosis. Toenail onychomycosis accounts for approximately 50 percent of nail onychodystrophy. Many patients are treated for onychomycosis without testing and may be at risk for mismanagement.51 It should be noted that fungi are secondary colonizers. While fungi may not be the primary cause of nail dystrophy, they may possibly be more opportunistic.52
Hanna and colleagues recommend that clinicians base the treatment for onychomycosis on the percentage of nail involvement.52 Topical efinaconazole is recommended for lesser involved cases with the addition or preference of oral terbinafine for more severe cases or when involvement is greater than three nails.
Many studies note that topical treatment with amorolfine, ciclopirox, tavaborole, or efinaconazole is appropriate for cases of mild to moderate toenail onychomycosis due to dermatophyte or mixed dermatophyte/Candida infection. However, the use of oral medication such as terbinafine, fluconazole and itraconazole is still the most efficacious.
Parasites: scabies. Scabies can cause thick, yellow, opaque nails with subungual debris. These findings are not unique to scabies and one may also see these findings in onychomycosis and inflammatory diseases. The diagnosis is based on clinical findings and demonstration of the mite microscopically.53
In Conclusion
Persistent single nail dystrophy or single nail onychomycosis that fails to improve may warrant additional investigation as to underlying causes. One must rule out many different conditions, including malignancies of the involved nail apparatus. Since tumors and nail cancer are possibilities, I recommend close monitoring of nail dystrophy quarterly. Typically, a nail will grow between three and 4.5 mm in that time frame. It is my belief that people do not look at their toenails as frequently as they look at their fingernails and will not spot changes as frequently. Podiatrists must use the aforementioned diagnostic tests to ensure a proper diagnosis. If the dystrophic nail is due in part to a foot deformity, orthotics and possible shoe gear changes can help lessen the trauma-induced symptoms. Surgical intervention to correct deformity may be necessary as well.
A dystrophic nail is not just a toenail that one needs to debride or trim. Clinicians need to evaluate these nails and ensure full treatment. Taking the necessary time to work up these patients and understanding that these nails are not all fungus may just keep patients on their feet and walking.
Dr. Morse is the Chair of the Scientific Planning Committee for the DERMfoot conference. He is board-certified by the American Board of Podiatric Orthopedics and Primary Podiatric Medicine as well as the American Board of Podiatric Surgery. Dr. Morse is in private practice in Washington, D.C.
1. Ishii L, Richmond NA, Carstens SJ, Vincek V. (2018). An amelanotic nail bed melanoma presenting as persistent onychodystrophy. Dermatology Online J. 2018;24(3). https://escholarship.org/uc/item/3jj8z264. Accessed July 29, 2019.
2. Haneke E. Important malignant and new nail tumors. J Dtsch Dermatol Ges. 2017;15(4):367-386.
3. Ho D, Mamalis A, Jagdeo J. Successful treatment of traumatic onychodystrophy and associated pterygium unguis with fractionated carbon dioxide laser: case report and review of the literature. J Drugs Dermatol. 2016;15(11):1461-1464.
4. Iorizzo M, Piraccini BM, Tosti A. Nail cosmetics in nail disorders. J Cosmet Dermatol. 2007;6(1):53-58.
5. Sehgel VN. Twenty nail dystrophy trachyonychia: an overview. J Dermatol. 2007;34(6):361-366.
6. Andre J, Moulonget I, Goetmann-Bonvallot S. In situ amelanotic melanoma of the nail unit mimicking lichen planus: a report of 3 cases. Arch Dermatol. 2010;146(4):418-421.
7. Nagar R, Nayak CS, Deshpande S, Gadkari RP, Shastri J. Subungual hyperkeratosis nail biopsy: a better diagnostic tool for onychomycosis. Indian J Dermatol Venereol Leprol. 2012;78(5):620-624.
8. Grover C, Chaturvedi UK, Reddy BS. Role of nail biopsy as a diagnostic tool. Indian J Dermatol Venereol Leprol 2012;78(3):290-298.
9. Grover C, Jakhar D. Onychoscopy: a practical guide. Indian J Dermatol Venereol Leprol 2017;83(5):536-549.
10. Jesús-Silva MA, Fernández-Martínez R, Roldán-Marín R, Arenas R. Dermoscopic patterns in patients with a clinical diagnosis of onychomycosis-results of a prospective study including data of potassium hydroxide (KOH) and culture examination. Dermatol Pract Concept. 2015;5(2):39–44.
11. Mundada P, Becker M, Lenoir V, et al. High resolution MRI of nail tumors and tumor-like conditions. Eur J Radiol. 2019;112:93-105.
12. Iorizzo M. Tips to treat the 5 most common nail disorders: brittle nails, onycholysis, paronychia, psoriasis, onychomycosis. Dermatol Clin. 2015;33(2):175-183.
13. Daniel CR 3rd, Tosti A, Iorizzo M, Piraccini BM. The disappearing nail bed: a possible outcome of onycholysis. Cutis. 2005;76(5):325–327.
14. Dias PCR, Miola AC, Miot HA. Successful management of chronic refractory onycholysis by partial nail avulsion followed by topical tretinoin. An Bras Dermatol. 2019;94(1):118–119.
15. Nath AK, Udayashankar C. Congenital onychogryphosis: leaning tower nail. Dermatol Online J. 2011;17(11):9. https://escholarship.org/uc/item/75n928bt. Accessed July 29, 2019.
16. Singh G, Haneef NS, Uday A. Nail changes and disorders among the elderly. Indian J Dermatol Venereol Leprol. 2005;71(6):386-392.
17. Shemer A, Daniel CR 3rd. Common nail disorders. Clin Dermatol. 2013;31(5):578-586.
18. Mathieu RJ, Vatanchi M, Heilman ER, Glick SA. A pediatric case of unusual melanocytic proliferation of the nail. Dermatol Online J. 2017;23(7). https://escholarship.org/uc/item/3s54b25d. Accessed July 29, 2019.
19. Ip KH-K, Oakley A (ed) Melanonychia. Derm Net Website. www.dermnetnz.org/topics/melanonychia. Published June 2014. Updated October 2017 by Elghblawi E, Oakley A. Accessed July 29, 2019.
20. Yahya H. Sparfloxacin-induced nail pigmentation: a case of fixed drug eruption? Ann Afr Med. 2018;17(1):40-42.
21. Alani A, Blasdale C, Oliphant T, Hackett C, Langtry JAA. The causes of nail apparatus pigmentation presenting to a melanoma screening clinic a prospective study. Clin Exp Dermatol. 2019;44(6):625-630.
22. Momen SE, Al-Niaimi F. Sarcoid and the nail: review of the literature. Clin Exp Dermatol. 2013;38(2):119-124.
23. Magdaleno-Tapial J, Valenzuela-Onate C, Ortiz-Salvador JM, Subiabre-Ferrer D, Hernandez-Bel P. Effective treatment of nail psoriasis with apremilast: report of two cases and review of the literature. Dermatol Online J. 2018;24(9). https://escholarship.org/uc/item/27x34947. Accessed July 29, 2019.
24. de Berker DA, Lawrence CM. A simplified protocol of steroid injection for psoriatic nail dystrophy. Br J Dermatol 1998;138(1):90-95.
26. Jaller JA, Jaller JJ, Jaller AM, et al. Recovery of nail dystrophy potential new therapeutic indication of tofacitinib. Clin Rheumatol. 2017;36(4):971-973.
27. Tosti A, Peluso AM, Fanti PA, Piraccini BM. Nail lichen planus: clinical and pathologic study of twenty-four patients. J Am Acad Dermatol. 1993;28(5 Pt 1):724-730.
28. Moreno-Coutino G, Fernandez-Martinez R, Sanchez-Moreno C, et al. Onychodystrophy: a possible marker for peripheral artery disease. J Vasc Nurs. 2016;34(1):24-26.
29. Baran R. The nail in the elderly. Clin Dermatol. 2011;29(1):54-60.
30. Loo DS. Onychomycosis in the elderly: drug treatment options. Drugs Aging. 2007;24(4):293-302.
31. Lacouture M, Sibaud V. Toxic side effects of targeted therapies and immunotherapies affecting the skin, oral mucosa, hair, and nails. Am J Clin Dermatol. 12018;9(Suppl 1):31-39.
32. Peuvrel L, Quereux G, Brocard A, Saint-Jean M, Dreno B. Onychopathy induced by temsirolimus, a mammalian target or rapamycin inhibitor. Dematology. 2012;224(3):204-208.
33. Paul LJ, Cohen PR. Paclitaxel-associated subungual pyogenic granuloma: report in a patient with breast cancer receiving paclitaxel and review of drug-induced pyogenic granulomas adjacent to and beneath the nail. J Drugs Dermatol. 2012;11(2):262-268.
34. Lau CP, Hui P, Chan TC. Docetaxel-induced nail toxicity: a case of severe onycholysis and topic review. Chin Med J (Engl). 2011;124(16):2559-2560.
35. Virgen CA, Belum VR, Kamboj M, et al. The microbial flora of taxane therapy–associated nail disease in cancer patients. J Am Acad Dermatol. 2018;78(3):607-609.
36. Robledo A, Godoy E, Manrique E, Manchado P. Retronychia: an underdiagnosed disease. Dermatol Online J. 2017;23(7). https://escholarship.org/uc/item/1gp4g3n2. Accessed July 29, 2019.
37. Park JH, Lee DY, Kim N. Nail neoplasms. J Dermatol. 2017;44(3):279-287.
38. Martinelli PT, Cohen PR, Schulze KE, Dorsey KE, Nelson BR. Periungual basal cell carcinoma: case report and literature review. Dermatol Surg. 2006;32(2):320-323.
39. Valero J, Gallart J, Gonzalez D, Deus J, Lahoz M. Subungual squamous cell carcinoma and exostosis in third toe--case report and literature review. J Eur Acad Dermatol Venereol. 2014;28(10):1292-1297.
40. Dika E, Starace M, Patrizi A, Fanti PA, Piraccini BM. Squamous cell carcinoma of the nail unit: a clinical histopathologic study and a proposal for classification. Dermatol Surg. 2019;45(3):365-370.
41. Neczyporenko F, Andre J, Torosian K, Theunis A, Richert B. Management of in situ melanoma of the nail apparatus with functional surgery: report of 11 cases and review of the literature. J Eur Acad Dermatol Venereol. 2014;28(5):550-557.
42. Nevares-Pomales OW; Sarriera-Lazaro CJ; Barrera-Llaurador J, et al. Pigmented lesions of the nail unit. Am J Dermatopathol. 2018;40(11):793-804.
43. Baran R, Kechijian P. Longitudinal melanonychia (melanonychia striata): diagnosis and management. J Am Acad Dermatol. 1989;21(6):1165-1175.
44. Leung AKC, Lam JM, Leong KF, Sergi CM. Melanonychia striata: clarifying behind the black curtain. A review on clinical evaluation and management of the 21st century. Int J Dermatol. 2019.DOI: 10.1111/ijd.14464
45. Lee DJR, Arbache ST, Quaresma MV, Nico MMS, Gabbi TVB. Nail apparatus melanoma: experience of 10 years in a single institution. Skin Appendage Disord. 2018;5(1):20-26.
46. Isales MC, Haugh AM, Bubley J, et al. Pigmented onychomatricoma: a rare mimic of subungual melanoma. Clin Exp Dermatol. 2018;43(5):623-626.
47. Poojary SA, Halwai V. A tumor hidden beneath the nail plate: report of a rare case of onychomatricoma with three-dimensional histopathological analysis and immunohistochemical study. Indian J Dermatol. 2015;60(2):212.
48. Rushing CJ, Ivankiv R, Bullock NM, Rogers DE, Spinner SM. Onychomatricoma: a rare and potentially underreported tumor of the nail matrix. J Foot Ankle Surg. 2017;56(5):1095-1098.
49. Keles MK, Yosma E, Aydogdu IO, Simsek T, Park TH. Multiple subungual pyogenic granulomas following levothyroxine treatment. J Craniofac Surg. 2015;26(6):e476-477.
50. Lambertini M, Piraccini BM, Fanti PA, Dika E. Mohs micrographic surgery for nail unit tumours: an update and a critical review of the literature. Eur Acad Dermatol Venereol. 2018;32(10):1638-1644.
51. Tolstrup J, Jemec GB, Hare RK, Arendrup MC, Saunte DM. [Diagnosing and treating of onychomycosis]. Ugeskr Laeger. 2018;180(20).
52. Hanna S, Andriessen A, Beecker J, et al. Clinical insights about onychomycosis and its treatment: a consensus. J Drugs Dermatol. 2018;17(3):253-262, 2018.
53. Oh S, Vandergfiff T. Scabies of the nail unit. Dermatology Online Journal. 2014:20(10). https://escholarship.org/uc/item/399489kr. Accessed July 29, 2019.
