The eponymously named dystrophy was first described in 1846 by Joseph Honore Simone Beau. Beau’s lines can be described as a “hiccup” in the mitotic machinery of the nail, the matrix epithelium (Fig. 22.6). A pause or halt of mitotic activity manifests as a depression along the transverse axis of the nail plate. As mitotic activity resumes, the line will progress, as many other nail disorders such as splinter hemorrhages do, as the nail plate extends. The significance of Beau’s lines is their ability to document the insult by the depth and length of the depression. Depth indicates the amount of damage to the matrix, and the length of the depression indicates the insult’s duration.

Beau’s lines can result singly from trauma. Suspicion for a drug-related or systemic cause should arise when Beau’s lines arise in multiple, (up to all 20) nails simultaneously, or present with repeated episodes. Beau’s lines are most often created by drugs that target the nail matrix epithelium or affect its highly active mitotic turnover. Therapeutic measures most commonly responsible for these events are chemoradiation therapy and retinoids. Theoretically, any chemotherapeutic drug can affect the body’s highly active epithelium, such as the gastrointestinal tract or nail matrix.

Onychomadesis is detachment of the nail plate occurring at the proximal nail bed or fold and subsequent shedding for the nail. Onychomadesis can occur when an insult, such as one creating Beau’s lines, is carried to its inevitable conclusion. In this setting, the insult creating mitotic arrest has become severe enough to result in structural instability of the nail plate, and the nail plate is detached while the new nail grows out.

Onychomadesis can occur spontaneously or after infections such as hand, foot, and mouth disease. Drug-induced onychomadesis can be due to a lengthening list of potential causes. Chemotherapeutics and retinoids inducing Beau’s lines can also be a cause of onychomadesis. There have also been reports of anticonvulsants such as carbamazepine and valproic acid causing onychomadesis.

While drugs have been well documented to cause onychomadesis, the possibility exists that severe drug allergy can also induce the process via an inflammatory route. Cases have been shown to occur, such as during critical illness. There exists a documented case of onychomadesis occurring following an allergic response to penicillin.

Onycholysis means the detachment of the nail plate from the nail bed. This process can occur from destruction of the nail bed’s viable epithelium or destruction of cell-to-cell adhesion molecules. Onycholysis, in contrast to onychomadesis, occurs distally from the nail bed or hyponychium, rather than proximally at the nail fold and nail matrix. It manifests as transverse white discoloration of the nail and is common in psoriasis.

Onycholysis has been associated with infection, trauma, psoriasis, photo reactions, and drugs (Table. 22.1). Drugs have been shown to cause onycholysis in combination with photo exposure, or as a sole agent. Therapeutics causing onycholysis include tetracyclines, fluoroquinolones, and psoralens.

True leukonychia (transverse) results from damage to keratinocytes in the distal nail matrix, which causes failure of maturation and retention of nuclei. Thus, transverse leukonychia occurs from the reflection of light, and is characterized by 1–2 mm transverse bands (each nail can have one or more). Affected nails will present with transverse leukonychia at the same site, indicating simultaneous damage to matrix keratinocytes (Fig. 22.7). The most common cause of transverse leukonychia is chemotherapy agents, most commonly doxorubicin, cyclophosphamide, and vincristine. Other agents include arsenic, fluorine, retinoids, cortisone, sulfonamides, pilocarpine, and trazodone. Arsenic and thallium poisoning will both present with transverse leukonychia involving the entire width of the nail plate.

Apparent leukonychia results from drug-induced damage to the nail bed. Alterations of blood flow to the nail bed will cause changes from the normal pink color seen. Half-and-half nails show proximal white discoloration of the nail that blends with the lunula (and distal portion retains the pink color). Muehrcke’s lines are transverse white bands that alternate with bands of normal pink colored nail bed (Fig. 22.8).

Drug-induced damage to melanocytes in the nail matrix can stimulate melanin production, particularly in darker-skinned individuals (Figs. 22.9 and 22.10). Longitudinal melanonychia results from stimulation of a small cluster of melanocytes, whereas the entire nail plate develops pigmentation if there is diffuse melanocyte activation. This is a common side effect of chemotherapy; in fact, repeated cycles can produce transverse leukonychia (suggesting intermittent melanocyte stimulation corresponding to the rounds of chemotherapy). Bleomycin, cyclophosphamide, doxorubicin, daunorubicin, fluorouracil (also lunular pigmentation), and hydroxyurea (also lunular pigmentation) are most commonly associated with melanonychia. Other sources of melanonychia include psoralens, methotrexate, radiation therapy, imatinib, and zidovudine (which can present with diffuse dark brown melanonychia or blue lunula).

Drug-induced melanonychia is generally reversible, though the clinician should be aware that it can takes years after cessation of the offending drug for melanin production to stop. This has to be distinguished from melanoma of the nail unit (subungual melanoma) that also presents with melanonychia (Fig. 22.11). The clinical presentation with the irregular pigmentation and involvement of the adjacent nail fold (Hutchinson sign) can help to distinguish melanoma from drug-induced pigmentation. In clinically ambiguous cases, a biopsy of the nail matrix and nail bed can be useful.

Drug excretion of deposition within the nail plate can cause pigmentation changes independent of melanocyte stimulation. Discoloration occurs in the nail plate and/or the nails (Tables. 22.2 and 22.3).