Yellow nail syndrome treated with itraconazole and vitamin E: A case report

Dear Editor, Yellow nail syndrome (YNS) is an uncommon condition characterized by thick yellow nails, usually accompanied by lymphedema and respiratory affectation. Its pathogenesis remains unclear, and currently, there is no consensus regarding treatment options. We present the case of a previously healthy 27-year-old female with a query diagnosis of YNS who had recently immigrated to Canada. According to her, she had a 6-year history of nail changes along with chronic cough without improvement despite several treatments. Her symptoms developed 6 months after being exposed to cosmetics made in a compounding pharmacy from her country of origin (West of Asia). The patient was previously evaluated by several physicians, and the diagnoses of onychomycosis and psoriasis were ruled out after multiple negative fungal cultures and a nail biopsy. She also failed treatment with systemic antifungal agents and oral methotrexate. At the time of our consultation, she had been free of treatment for at least 6 months. Her physical examination showed yellowish discoloration and severe thickening of all 20 nails with the absence of the lunulae and cuticles and onycholysis of one fingernail [Figure 1]. A new nail fungal culture was negative, and a further respiratory assessment was also negative for bronchiectasis but consistent with asthma. She had no current history of lymphedema. Blood levels of trace elements (mercury, nickel, and TiO2) were within normal limits; however, analysis of her nail clippings demonstrated elevated levels of TiO2 (2.23 μg/g), mercury (14.5 μg/g), and nickel (29.86 μg/g) which suggested the diagnosis of YNS. As part of her treatment, we recommended avoiding TiO2 exposure and prescribed vitamin E 1000/U/day plus itraconazole 400 mg daily for 1 week every month. In addition, a budesonide/formoterol fumarate dihydrate inhaler and nasal mometasone spray were recommended by the respirologist.Figure 1: Severe thickening and yellowish discoloration of all 20 nails.Nail regrowth was evident after a few months, with a complete resolution after 10 months [Figure 2]. Her respiratory symptoms also subsided, although she continued having some occasional flares. Vitamin E and itraconazole were discontinued after she completed 14 months of treatment without any sign of recurrence.Figure 2: Complete resolution after 1 year of treatment.YNS is an uncommon condition mainly characterized by a severe impairment of nail growth that leads to severe nail thickness with yellow discoloration. Respiratory diseases and lymphedema may accompany nail affectation, forming a triad; however, it is currently accepted that only two features of this triad are necessary to make the diagnosis, as only 20%–67% of patients present the three features.[1] It is thought that the appearance of the nails results from an impairment of the rate of nail growth (<0.25 mm/week) that leads to the accumulation of lipofuscin pigments.[2] Respiratory symptoms associated with YNS may include chronic cough, sinusitis, bronchiectasis, pleural effusion, and recurrent pneumonia.[3] Interestingly, asthma, like in our patient, had not previously been reported. Lymphedema occurs in 30%–80% of patients with YNS and typically manifests in the bilateral lower extremities;[4] however, our patient did not show this feature. Current literature suggests that TiO2 exposure could cause YNS because it has been demonstrated that patients with YNS show elevated levels of TiO2 in the nails after a history of TiO2 exposure through dental implants, drugs, or food.[5] However, although our patient also presented with high levels of TiO2 in her nails, the nail levels of mercury and nickel were even higher, even though she did not have a history of chronic metal exposure or symptoms that suggest toxicity. Therefore, although we cannot completely rule out that TiO2 has a role in developing this condition, we think that high levels of TiO2 and other elements in her nails resulted from a chronic accumulation due to the lack of nail growth rather than the actual trigger. In addition, it is unclear why only a few people develop YNS while TiO2 exposure is unavoidable. Although TiO2 has been recently banned in some countries due to concerns about its genotoxicity, TiO2 is still found in everyday products, including cosmetics, dental and orthopedic implants, drugs, paint, and foods such as candies, pastries, chewing gum, coffee creamers, chocolates, and cake decorations.[6] We selected itraconazole and vitamin E as treatments based on previous case reports. In addition to its antifungal effects, itraconazole has been demonstrated to increase nail rate growth by increasing the number of proliferating cells in the nail matrix.[7] At the same time, vitamin E has antioxidant properties that potentially block lipofuscin pigment production, which may cause yellow pigmentation.[8] Fortunately, the patient’s nails showed complete resolution 1 year after treatment. Still, more studies are needed to determine the most effective treatment and the true origin of this condition. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement All data generated or analyzed during this study are included in this published article. Financial support and sponsorship This was a self-funded study. Conflicts of interest There are no conflicts of interest.

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