Yellow nail syndrome: A rare entity.

Sir,

Yellow nail syndrome (YNS) is a rare disorder characterized by classical triad of deformed yellow nail, primary lymphedema, and recurrent pleural effusion. Lymphatic obstruction due to anatomical or functional abnormality of lymphatic vessels.[1] It was first described by Samman and White in 1964 with features of primary lymphedema and yellowish discoloration of nails.[2] Pleural effusion as a feature of this syndrome was added later.

A 50-year-old male patient presented with gradually progressive swelling of both lower limbs for last 10 years and cough with breathlessness off and on for the past six years. Twenty years ago, he noted yellowish discoloration of finger and toenails, which were also thickened and very slow growing. He was hospitalized twice previously, in 2003 and 2006, for breathlessness and bilateral lower limb swelling. On both occasions, X-ray chest showed mild pleural effusion that responded well to antibiotics, but lower limb swelling persisted. A week prior to presentation, chest X-ray showed bilateral (right >left) mild pleural effusion, but the patient did not respond to antibiotics and 500 ml straw colored fluid was aspirated from the right pleural cavity. He was nondiabetic, normotensive, and nonsmoker with no history of lymphangitis, cardiomyopathy, or tuberculosis.

Physical examination revealed generalized wasting, pallor with bilateral nonpitting pedal edema and normal vital parameters. All finger and toenails were yellowish, thickened, and curved [Figures 1 and 2]. The nails were curved from side to side, yellow in color and lunulae were not seen. Periungual tissues were swollen and cuticles were not visible. Respiratory system examination revealed a dull percussion note and diminished breath sounds on bilateral lower lung field (right >left side).

Figure 1

Yellowish discoloration and thickening of the finger nails

Figure 2

Yellowish toenails and bilateral pedal edema

Chest X-ray showed bilateral pleural effusion more on the right side [Figure 3]. Blood test revealed hypoalbuminemia (2.0 g/dl) and hypoproteinemia (3.9 g/dl). Blood for HIV, HBsAg, HCV, and filarial antigen were negative. Blood gas analysis showed mild hypoxemia. Stool analysis and d-xylose test were normal. Sputum for acid-fast bacillus (AFB) and culture were negative. Mantoux test was negative. radiograph of the paranasal sinuses, barium meal, upper gastrointestinal endoscopy with D2 biopsy, colonoscopy, barium meal follow through and enema, electrocardiogram, and echocardiogram were normal. Abdominal ultrasound scan was normal. Doppler ultrasound of lower limb showed bilateral normal venous flow. Nail scraping for fungal growth was negative.

Figure 3

Chest radiograph showing bilateral pleural effusion

Thoracocentesis revealed 800 ml of straw colored fluid with pleural fluid lactate dehydrogenase (LDH) to serum LDH ratio >0.6 and pleural fluid protein to serum protein ratio >0.5 compatible with diagnosis of exudative pleural effusion. The total cell count in the fluid was low and the cells were mainly lymphocytes. Cholesterol, triglycerides, and amylase level (44 mg/dl) of the pleural fluid were persistently normal [Table 1]. Pleural fluid was negative for AFB, Mycobacterium tuberculosis polymerase chain reaction, mycobacterial growth, pyogenic organisms, and fungi. Pleural biopsy also revealed normal findings. A chest computed tomography scan after thoracocentesis revealed bilateral moderate pleural effusion with passive collapse of both lower lobes. Bronchoscopy was unremarkable. Bronchial aspirates were negative for bacterial, mycobacterial growth, and PAP smear.

Table 1

Pleural fluid findings over time

Repeated aspiration of pleural fluid failed to improve symptoms and tetracycline pleurodesis was done after closed tube thoracostomy on the right side leading to marked reduction in pleural effusion and dyspnea. In this case, recurrent pleural effusion, bilateral nonpitting pedal edema and yellow nail prompted us to make the diagnosis of YNS.

Yellow nail syndrome usually presents as primary lymphedema, recurrent pleural effusion, and yellowish discoloration of the nail. Two of these symptoms are required for the diagnosis, since the complete triad is only observed in about one-third of patients.[3] Since the original description by Samman and White many associations of YNS have been described.[2] This syndrome may have associated bronchiectasis, sinusitis, pericardial effusion, chylous ascites, etc.[4] YNS is frequently reported with autoimmune thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, hypogammaglobulinemia, protein losing enteropathy and various malignancies such as breast, larynx, lung, endometrium, gallbladder, and Hodgkin's lymphoma.[5] Dixit et al. have reported a case of YNS in a male patient taking medication for tuberculous pleural effusion with category III revised national tuberculosis control program.[6]

The basic abnormality of YNS is hypoplasia of the lymphatics, which is responsible for lymphedema, pleural effusion, and nail changes. In the majority of cases, lymphangiography demonstrates hypoplastic, deficient, and sclerotic lymphatic vessels; yellow nail occurs due to altered arterial circulation and Raynaud's disease. Hypoalbuminemia and protein losing enteropathy are due to lymphatic leakage of protein and it is also associated with increased capillary permeability of the walls of villi.[5]

Onycholysis, yellowish green, thickened, and excessively curved nails are found in most cases of YNS. Oral and topical vitamin E and clarithromycin are useful in the management of nail abnormality. Intralesional steroid is also effective. Primary lymphedema affects the lower extremity. Pleural effusion is exudative, lymphocytic predominant, bilateral and recurrent in the majority of cases.

In this case, diagnosis of YNS was obvious due to the presence of triad namely yellowish thickened nails, primary lymphedema and recurrent bilateral pleural effusion. Sometimes all features may not be present simultaneously; the presence of yellow nails may solve the diagnostic dilemma in such cases.