Yellow nails under bucillamine therapy for rheumatoid arthritis: a report of two cases

Abstract

To the editor, Although yellow nail syndrome is occasionally associated with various conditions, rheumatoid arthritis (RA) is the most frequently seen disorder [1–8], particularly in patients treated with D-penicillamine, bucillamine, thiol and gold. We report herein two cases with severe RA who developed yellow nails coinciding with bucillamine therapy. Although both cases did not present lung involvement, we must be aware that bucillamine can cause yellow nails. Case 1 was a 50-year-old female with RA. She visited the Dermatology Department of Tokyo Metropolitan Bokuto Hospital, complaining of yellowish changes of Wngernails (Fig. 1a). Increased transverse curvature was also seen. Fungal infection was denied by KOH examination. Further physical examination revealed yellowish changes of her toenails. She had been treated for RA with several drugs including bucillamine for some months, and total dose of bucillamine was 60 g. Neither lymphedema nor chronic pleural eVusion was observed. Laboratory examination showed positive rheumatoid factor, RAPA, and an increased ESR (45 mm/h), but otherwise normal. We suspected that bucillamine might have induced these nail changes. During the course, bucillamine was stopped. Eight months later, her Wngernails were all returned to normal color. Case 2 was a 76-year-old female with RA. She had received nearly 150 g bucillamine for over 1 year. She had noticed yellowish changes of her Wngernails earlier than she visited the Department of Dermatology of Tokyo Medical and Dental University. Physical examination revealed gold to yellowish discoloration of all the toenails and Wngernails (Fig. 1b). KOH test was negative. Neither lymphedema nor chronic pleural eVusion was observed. Laboratory examination showed an increased ESR (94 mm/h), positive rheumatoid factor, RAPA (x2560), and C-reactive protein (8.0 mg/dl). Serum anti-nuclear antibody was negative. Yellow nail syndrome is characterized by the presence of nail alterations, peripheral lymphedema and pulmonary abnormalities. Seventy percent of the patients were female. Lung manifestations are mainly pleural eVusions or bronchiectasis; however, one-third had no pulmonary involvement. Nail changes of yellow nail syndrome include yellow discoloration, very slow growth, hardening of the nail plate and loss of cuticles, and aVect all Wngernails and toenails. Although yellow nail syndrome is occasionally seen in connection with autoimmune disorders, immunodeWciency states, nephrotic syndrome, and Guillain-Barre syndrome, yellow nails are also induced with the use of certain drugs such as D-penicillamine, thiol and gold. Bucillamine is an analogue of D-penicillamine, and its mode of action is similar to that of D-penicillamine. D-penicillamine and bucillamine share a cysteine-like structure. Cysteine is a major compound of nails. Therefore, because of the chemical similarity to cysteine, both drugs may aVect nail keratinization by a competition phenomenon. T. Yamamoto · H. Yokozeki Department of Dermatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan