Nailing the Diagnosis!

Article Outline

• Clinical Summary
• Discussion
• Conclusions
• References
• Copyright

Physical examination plays a crucial role in patient evaluation by confirming the hypotheses during history taking, suggesting new clues, and directing investigations. We describe how the recognition of a nail abnormality led us to the recognition of the cause of long-standing lymphedema and pleural effusion.

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Clinical Summary 

A 41-year-old male farmer presented with dyspnea and cough of 4 years duration and bilateral pedal edema of 20 years duration. Pedal edema was bilateral, gradual in onset, persistent, and painless, and had reduced in intensity over the last 3 years. Breathlessness had increased gradually, and he was breathless on performing daily work at the time of evaluation. He denied any smoking, drug abuse, significant family history, or high-risk behavior. He was married with no children. He was evaluated in another hospital earlier where investigations had revealed bilateral pleural effusions. On the basis of the pleural fluid characteristics, antitubercular therapy was administered for 6 months. However, pleural effusion and breathlessness had increased on this treatment, and bilateral intercostal tube drainage was performed. The patient's course was complicated by persistent drainage, empyema, loculated pleural collections, and worsening respiratory distress. He was referred to this center for evaluation.

On evaluation, the patient was febrile, drowsy, normotensive with a respiratory rate of 26 breaths/min, pulse rate of 110 beats/min, and central cyanosis. Examination showed bilateral nonpitting edema with skin thickening and left-sided hydrocele. He had yellow dystrophic nails with subungual hyperkeratosis in both upper limbs. There was no evidence of fungal infection of the fingers (Figure 1). Chest auscultation revealed coarse crackles with reduced intensity of breath sounds bilaterally. The right chest tube was draining pus with no evidence of bronchopleural fistula. The left chest tube was draining approximately 150 mL of clear fluid per day. Hemogram showed microcytic hypochromic anemia (hemoglobin of 10 g/dL) and leukocytosis (leukocyte count of 15,600/μL). Serum albumin and renal function test results were normal. Urine examination did not show any evidence of proteinuria. Human immunodeficiency virus enzyme-linked immunosorbent assay, antinuclear antibody, thyroid function test results, filarial serology, and abdominal fat pad for amyloidosis were all negative. Echocardiography showed mild pericardial effusion and mild mitral and tricuspid regurgitation with normal ejection fraction (55%). Blood, urine, and sputum cultures were sterile. The right chest drain cultures isolated Klebsiella pneumoniae sensitive to cefoperazone-sulbactam. The left chest drain analysis yielded a lymphocytic exudative effusion (glucose 65 mg/dL, protein 3.4 g/dL, adenosine deaminase 12 U/L) with normal adenosine deaminase levels. Chest radiographs showed bilateral loculated pleural effusions with chest drains in situ. Computed tomography of the chest confirmed the above and showed a small pericardial effusion and small mediastinal lymph nodes. There was no evidence of bronchiectasis (Figure 2). Arterial blood gas analysis showed evidence of acute on chronic type 2 respiratory failure (pH 7.33, HCO₃ of 34 mg/dL, Paco₂ of 55 mm Hg, and Pao₂ of 45 mm Hg).

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• Figure 1. 

  Both hands of patient showing yellow dystrophic nails in both thumbs. Subungual hyperkeratosis is present, and there is no evidence of fungal infection of the fingers.

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• Figure 2. 

  Composite images of the coronal reconstructed images of computed tomography of the chest with mediastinal (A) and lung (B) windows showing bilateral loculated pleural effusions, drain in situ on the left side, pericardial effusion, and small mediastinal lymph nodes.

A diagnosis of yellow nail syndrome with bilateral pleural effusions, right loculated empyema, and sepsis with respiratory failure was made. The yellow nail or Samman-Emerson syndrome consists of the triad of deformed yellow nails, lymphedema, and pleural effusions.¹ A wide variety of other manifestations have been reported. We performed a systematic search in the PUBMED and CINAHL databases using the terms “yellow nail syndrome” and “yellow nail” and collected data on all reported manifestations of this syndrome (Table 1). Given the lack of understanding of the pathogenesis of this condition, the diagnosis remains clinical. The pathognomic clinical features can appear at varying times, and only 2 of the 3 findings are required for the diagnosis of this syndrome. No more than 10% of patients have all 3 features at the time of diagnosis.

Table 1. Manifestations of Yellow Nail Syndrome

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Discussion 

The cause of this syndrome remains obscure. Familial cases of yellow nail syndrome have been reported; however, no genetic linkages have been made and most cases are acquired.² Although the syndrome occurs mostly in isolation, associations occur with a wide variety of conditions (Table 2). Rheumatoid arthritis is the most common associated condition. A PUBMED search using the terms “rheumatoid arthritis” and “yellow nail syndrome” yielded 16 cases. Most of these were associated with drug intake (gold and penicillamine). Malignancies are the other major association with this syndrome, and the resolution of yellow nails with successful therapy of the underlying malignancy also has been reported.³ No gender predominance has been noted in a large series.

Table 2. Causes of Yellow Nails Reported in Medical Literature

The pathophysiology of the syndrome remains unclear, but theories include various anatomic or functional lymphatic drainage abnormalities¹ and microvasculopathy with protein leakage.⁴ Lymphangiograms of the lower extremity demonstrate hypoplasia of at least some lymphatic vessels in most patients with the syndrome.¹, ² It has been postulated that pleural effusions may develop when respiratory tract infection or pleural inflammation damages subclinically impaired lymphatic vessels.

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. The actual color may be pale yellow to greenish. Onycholysis is frequently present. The yellow nails spontaneously resolve in 56% of cases over time.² Yellow nails also are reported in several other conditions apart from yellow nail syndrome and are not pathognomic in isolation (Table 2). Lichen planus of the nail⁵ and onychomycosis may be confused with the nail changes in this syndrome. Lymphedema of various degrees is seen in 63% of the reported cases and also might regress over time. Pleural effusions are found in 48% of patients. The pleural effusions are bilateral in approximately 50% of patients, and they persist and recur rapidly after a thoracentesis. The pleural fluid is usually a clear yellow exudate with a normal glucose level containing predominantly lymphocytes. However, transudates and chylothoraces also are reported.

The treatment of this syndrome is anecdotal. Vitamin E has been proposed as treatment based on positive experiences in patients with other dermatologic conditions assumed to result from deficient microvascularity.⁶ However, consistent benefit has not been observed with vitamin E, and fortuitous improvement in the nails may be attributed to treatment. Decongestion has been used for the management of lymphedema, and anecdotal reports of improvement in the nails exist. Recalcitrant effusions may require either pleuroperitoneal shunting or drainage with talc pleurodesis.² Optimum management of bronchiectasis by rotation of antibiotics, postural drainage, inhaled bronchodilators, influenza and pneumococcal immunizations, and prompt treatment of complicating respiratory infections is associated with improvement in the syndrome.²

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Conclusions 

Respiratory failure was managed with low tidal volume mechanical ventilation, and sepsis was managed per the surviving sepsis guidelines. Pleurodesis was performed on the left side, and the drain was removed. The patient underwent decortication on the right side, after which he improved and was extubated successfully. He was administered oral vitamin E 400 mg/d. He could climb 2 flights of stairs without difficulty after 4 months of discharge; however, his nail changes and minimal lymphedema have persisted after 6 months of vitamin E treatment.

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References 

1. Samman PD, White WF. The “yellow nail” syndrome. Br J Dermatol. 1964;76:153–157
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2. Maldonado F, Tazelaar HD, Wang CW, Ryu JH. Yellow nail syndrome: analysis of 41 consecutive patients. Chest. 2008;134:375–381
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3. Iqbal M, Rossoff LJ, Marzouk KA, Steinberg HN. Yellow nail syndrome: resolution of yellow nails after successful treatment of breast cancer. Chest. 2000;117:1516–1518
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4. D'Alessandro A, Muzi G, Monaco A, Filiberto S, Barboni A, Abbritti G. Yellow nail syndrome: does protein leakage play a role?. Eur Respir J. 2001;17:149–152
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5. Baran R. Lichen planus of the nails mimicking the yellow nail syndrome. Br J Dermatol. 2000;143:1117–1118
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6. Ayres S, Mihan R. Yellow nail syndrome: response to vitamin E. Arch Dermatol. 1973;108:267–268
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