Yellow nail syndrome

Resolution of Yellow Nails After Successful Treatment of Breast Cancer

Yellow nail syndrome (YNS) is a rare entity of unknown cause in which congenitally hypoplastic lymphatics play a major role in the clinical manifestations of the disease. YNS has been associated with many malignancies and immune disorders. We report a case of new-onset YNS associated with breast cancer and dramatic improvement in the yellow nails with cancer treatment.

(CHEST 2000; 117:1516-1518)

Key words: carcinoma of breast; chemotherapy; neoplasm; yellow nail

Abbreviation: YNS = yellow nail syndrome

Yellow nail syndrome (YNS) is a rare disorder, characterized by rhinosinusitis, pleural effusions, bronchiectasis, lymphedema, and dystrophic yellow nails.[1,2] The classic triad, described by Emerson, of lymphedema, slow-growing yellow nails, and pleural effusion is seen in only one third of patients.[3,4] More than 150 cases attributed to congenitally hypoplastic lymphatics are reported in the literature. Individual manifestations of the syndrome can appear at different times, and clinical onset varies from birth to late adult life.[5] YNS has been associated with autoimmune disorders, such as thyroiditis, systemic lupus erythematosus, and rheumatoid arthritis.[5] There are also isolated case reports of YNS associated with malignancies in cancer of the breast,[5] larynx,[6] lung,[7] endometrium,[8] gall bladder,[9] metastatic sarcoma,[10] metastatic melanoma,[11] Hodgkin's disease,[12] and mycosis fungoides.[13] It has also been described in tuberculosis, AIDS, and other immunodeficiency states, and with the use of certain drugs.[14]

We report what we believe to be only the second case of breast cancer in which the yellow nails remitted after treatment.[5] In this case, unlike the previous one, nail changes were restricted to the upper extremities.

CASE REPORT

A 62-year-old woman presented with chronic cough of 1.5 years' duration. The cough was worse in the morning and intermittently productive of purulent sputum. Her pulmonary symptoms transiently responded to antibiotics but recurred about 2 to 3 weeks after their cessation. She also complained of chronic nasal congestion and postnasal drip but denied wheezing, skin disease, or other evidence of atopy and reported only one remote episode of lobar pneumonia. She also noted progressive yellowing of the nailbeds of both hands for several months before presentation. She denied corticosteroid use or evidence of immune deficits. There was no history of swallowing dysfunction, and her weight and appetite remained stable. She was on thyroid replacement therapy subsequent to a thyroidectomy (1964) for goiter and Hashimoto's thyroiditis. She ceased smoking 2 years before, with a total of 10 to 15 pack-years. Her family history was unremarkable.

On physical examination, she was found to have dystrophic yellow nails in both hands (Fig 1) with normal toenails. Chest auscultation revealed bilateral, scattered, coarse crackles in the lower zones. There was no evidence of peripheral edema. The rest of the examination was not revealing. CT scan of the sinuses showed opacification of both maxillary sinuses and mucosal thickening of both sphenoid sinuses. High-resolution CT scan of the chest (Fig 2) showed mild cylindrical bronchiectasis mainly in the right lower lobe with subsegmental atelectasis in the right middle lobe and lingula. Also seen on this image was an unsuspected mass in the right breast measuring 1 x 1.5 cm with associated axillary lymphadenopathy. Excisional biopsy revealed an infiltrating ductal carcinoma of the breast positive for estrogen and progesterone receptors. Axillary lymph node dissection confirmed tumor nodal involvement (T1N1M0). She was treated with monthly cycles of cyclophosphamide, methotrexate, and 5-flurouracil for 8 months. She quickly noted improvement in her dystrophic yellow nails, which appeared normal by the end of the chemotherapeutic regimen (Fig 1). She subsequently received radiation therapy and tamoxifen. In subsequent 2 year follow-up, there is no recurrence of tumor or yellow nails.

[Figures 1-2 ILLUSTRATION OMITTED]

DISCUSSION

Since the original description by Samman and White,[15] many associations of YNS have been described. Airway manifestations include rhinosinusitis and bronchiectasis. Yellow nails result from slow growth, possibly secondary to defective lymphatic drainage. The nails become dystrophic with longitudinal or transverse ridging and loss of lunula and cuticles.[16] Pleural effusions appear to be a later manifestation of the syndrome secondary to inadequate drainage by overstressed hypoplastic lymphatics rather than increased fluid production.[17] The cause of bronchiectasis is unclear, but again, dysfunctional lymphatics are thought to play an important role with compromised drainage of secretions and local immune function.[18]

Various malignancies have been associated with YNS, and one case of the yellow nails improved dramatically after resection of a laryngeal cancer.[19] As in our case, Gupta et al[5] reported similar improvement after surgery and chemotherapy for a carcinoma of the breast. Interestingly, improvement was seen in the fingernails only. Although partial or complete improvement in the nails may occur spontaneously in up to one third of patients, the temporal relationship and pace of the improvement strongly favors an association with successful treatment of malignancy. Possible explanations include direct involvement by tumor of already stressed and dysfunctional lymphatics or the elaboration of mediators such as peptide hormones that inhibit lymphatic function.[7] Thus, yellow nails may be a paraneoplastic manifestation of cancer that may resolve with effective treatment. The diagnosis of YNS should raise the index of suspicion for malignancy and other associated diseases.

REFERENCES

[1] Norkild P, Kroman-Anderson H, Struve-Christensen E. Yellow nail syndrome: the triad of yellow nails, lymphedema and pleural effusion. Acta Med Scand 1986; 219:221-227

[2] Varney VA, Cumberworth V, Sudderic R, et al. Rhinitis, sinusitis and the yellow nail syndrome: a review of symptoms and response to treatment in 17 patients. Clin Otolaryngol 1994; 19:237-240

[3] Emerson PA. Yellow nails, lymphedema and pleural effusion. Thorax 1966;21:247-253

[4] Pavlidakey GP, Hashimoto K, Blum D. Yellow nail syndrome. J Am Acad Dermatol 1984; 11:509-512

[5] Gupta AK, Davies GM, Haberman HF. Yellow nail syndrome. Cutis 1986; 37:371-374

[6] Guin JD, Elleman JH. Yellow nail syndrome: possible association with malignancy. Arch Dermatol 1979; 115:734-735

[7] Thomas PS, Sidhu B. Yellow nail syndrome and bronchial carcinoma [letter]. Chest 1987; 92:191

[8] Mambretti-Zumwalt J, Seidman JA, Higano N. Yellow nail syndrome: complete triad with pleural protein turnover studies. South Med J 1980; 73:995-997

[9] Burrows NP, Jones RR. Yellow nail syndrome in association with carcinoma of gall bladder. Clin Exp Dermatol 1991; 16:471-473

[10] Hiller E, Rosenow EC, Olsen AM. Pulmonary manifestations of the yellow nail syndrome. Chest 1972; 61:452-458

[11] Emerson PA. Yellow nails, lymphedema and pleural effusions. Thorax 1966; 21:247-253

[12] Siegelman SS, Heckman BH, Hasson J. Lymphedema, pleural effusions and yellow nails: associated immunologic deficiency. Dis Chest 1969; 56:114-117

[13] Stosiek N, Peters KP, Hiller D, et al. Yellow nail syndrome in a patient with mycosis fungoides. J Am Acad Dermatol 1993; 28:792-794

[14] Hershko A, Hirshberg B, Nahir M, et al. Yellow nail syndrome. Postgrad Med J 1997; 73:466-468

[15] Samman PD, White WF. The `yellow nail syndrome.' Br J Dermatol 1964; 76:153-157

[16] Ilchyshyn A, Vickers CH. Yellow nail syndrome associated with penicillamine therapy. Acta Derm Venereol 1983; 63:554-555

[17] Runyon BA, Forker EL, Sopko GA. Pleural-fluid kinetics in a patient with primary lymphedema, pleural effusions, and yellow nails. Am Rev Respir Dis 1979; 119:821-825

[18] Wiggins J, Strickland B, Chung KF. Detection of bronchiectasis by high-resolution computed tomography in the yellow nail syndrome. Clin Radiol 1991; 43:377-379

[19] Guin JD, Elleman JH. Yellow nail syndrome: possible association with malignancy. Arch Dermatol 1979; 115:734-735

(*) From the Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, New Hyde Park, NY.

Manuscript received July 20, 1999; revision accepted October 18, 1999.

Correspondence to: Leonard J. Rossoff, MD, Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, The Long Island Campus of the Albert Einstein College of Medicine, Room C-20, 270-05 76th Ave, New Hyde Park, NY 11042

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