Peer Reviewed

Pulmonary Disorders

What Caused This Man’s Chronic Cough and Discolored Nails?

Gena Han, DO1 • Timothy Leisching, MD1,2

1Pulmonology Department, Beth Israel Lahey Health, Burlington, Massachusetts
2Chief Medical Officer, Lahey Hospital & Medical Center, Burlington, Massachusetts

Han G, Leisching T. What caused this man’s chronic cough and discolored nails? Consultant. 2021;61(11):e19-e21. doi:10.25270/con.2021.04.00012

Received November 19, 2020. Accepted December 28, 2020. Published online April 21, 2021.

The authors report no relevant financial relationships.

Gena Han, DO, Beth Israel Lahey Health, Attn: Pulmonary and Critical Care, 41 Mall Road, Burlington, MA 01805 (


A 66-year-old man was referred to our clinic for evaluation of cough, fevers, and rigors that had progressed over 10 days. His sputum was purulent but without hemoptysis. His medical history was significant only for a similar episode of pneumonia, which was resolved with antibiotics 1 year earlier.

A physical examination revealed crackles auscultated in the chest over the right middle lobe anteriorly, trace bilateral lower extremity shin lymphedema, and yellow-discolored nails (Figure). A chest radiograph demonstrated focal consolidation consistent with pneumonia of the right middle lobe.

Figure. The patient's discolored, brittle nails.
Figure. The patient’s discolored, brittle nails.


As the current infiltrate was the patient’s second such episode, a computed tomography (CT) scan of the chest was performed, results of which demonstrated multifocal consolidation and scattered ground glass opacities without pleural effusions. The patient was given azithromycin, 250 mg, daily.

Two months later, the patient presented with persistent cough. At that time, the cough had been present for 6 weeks and was characterized as dry. The patient also had rhinorrhea with postnasal drip, night sweats, and weight loss of 8 lbs. A chest examination demonstrated clear lung fields. Otherwise, the physical examination had been unchanged since his first presentation.

A repeat CT chest scan demonstrated resolution of the previously noted multifocal consolidations, but the scattered ground glass opacities were unchanged. In addition, bronchiectasis was evident.

The chronic cough coupled with persistent ground glass opacities seen on chest CT scans prompted a bronchoscopy. Bronchoalveolar lavage samples demonstrated a cell count differential with 81% neutrophils and negative cultures, including a negative acid-fast bacillus stain and culture.

Transbronchial biopsies showed focal perivascular chronic inflammation without evidence of malignancy. The patient was started on scheduled guaifenesin and fluticasone nasal spray, and he was shown how to use a flutter valve.

At a follow-up visit several months later, the chronic cough had continued with the interval development of significant sinus drainage, as well as a small right pleural effusion.



Answer and discussion on next page.

Answer: C. Yellow nail syndrome

Discussion. The differential diagnoses for yellow nail syndrome include planus lichen, chronic paronychia, and alopecia areata.1 Exposure to certain drugs or toxins, such as D-penicillamine, epoxy, chromium salts, and pesticides, may also cause yellow nail syndrome.1 Infectious etiologies can include chloronychia caused by Pseudomonas aeruginosa, Candida, aspergillus, or dermatophytes.1

The diagnosis of yellow nail syndrome is one of exclusion and is made clinically based mainly on physical examination and radiographic findings. In the absence of an alternative diagnosis, 2 of the 3 classic findings—thick yellow nails, primary lymphedema, and pulmonary manifestations—are required to diagnose primary yellow nail syndrome.2-5 Yellow nail syndrome is also associated with malignancy, connective tissue diseases, hemochromatosis, Guillain-Barré syndrome, myocardial infarction, diabetes, and thyroid dysfunction.1,3,6-9

While the pathophysiology of yellow nail syndrome remains unclear, there are several proposed mechanisms of pathogenesis. Structurally, lymphatic hypoplasia and dilatation with collateral network formation can be seen but is not consistently described in all cases. More recently, it is thought that a functional disorder plays a larger role in the development of yellow nail syndrome.4 Microvasculopathy causing protein leakage with impaired lymphatic drainage is thought to be the cause of lymphedema and pleural effusion formation.4 Thickening of nails may also be due to ectatic lymphatic vessels, while the discoloration may be due to lipid oxidation leading to an accumulation of lipofuscin in the nails.4

Treatment and management. Management of yellow nail syndrome is variable and targeted at the specific manifestation of underlying disease process. Treatment for yellowing nails is typically systemic. Oral vitamin E, zinc, triazole antifungals, and clarithromycin have all been used with varying results and no effect on pulmonary manifestations. Addressing pulmonary symptoms include the use of antibiotics for acute bronchiectasis flares, maintenance with oral azithromycin 3 times weekly, and chest physiotherapy. If pleural effusions become symptomatic, treatment is warranted. Surgical options for recurrent effusions include decortication/pleurectomy, pleural-peritoneal shunts, and chemical pleurodesis. Of these options, decortication/pleurectomy has the highest partial or complete response rate at 89%.1,3,4

Lymphedema management is based on close attention to skin and nail care to prevent skin breakdown, which could allow introduction of infection. Use of compression garments, regular exercises, overnight bandaging, and manual lymph node drainage can also assist with improving lymphedema. The treatment of sinusitis in patients with yellow nail syndrome is equivalent to treatment for all chronic sinusitis patients with antibiotics and possible surgical intervention if needed.1

Nail changes may spontaneously resolve in about 30% of patients; unfortunately, remission of yellow nails does not portend remission of other systemic manifestations. Ongoing treatment of pulmonary and lymphedema symptoms may be necessary. If the yellow nail syndrome is due to an underlying malignancy, treating the malignancy may lead to improvement of yellow nail syndrome signs and symptoms. Overall, there is a decrease in the median survival of patients with yellow nail syndrome by 132 months compared with a paired control population.1

Patient outcome. On subsequent follow-up 1 year later, the patient reported that his nails were persistently yellow and slow growing, only needing to cut them once in the past year (Figure). Subsequent chest CT scans demonstrated small bilateral effusions. Findings from a transthoracic echocardiogram were unremarkable.

He underwent a positron-emission tomography scan, which resulted in no worrisome fluorodeoxyglucose update. Laboratory test results for cystic fibrosis, immunoglobulin deficiencies, and rheumatologic diseases also were negative. Given his negative test results and triad of chronic respiratory symptoms, yellow nails, and primary lymphedema, yellow nail syndrome was diagnosed based on excluding other diagnostic explanations.

The patient was prescribed oral vitamin E to treat his yellow nails; however, he continued to have slow-growing yellow nails. Maintenance azithromycin 3 times weekly was initiated given recurrent episodes of acute exacerbations of bronchiectasis, which were sometimes complicated by multifocal pneumonia. Mucus clearance measures were also initiated, including a flutter valve, nebulized bronchodilators, and a chest percussion device. The patient’s pleural effusions remained small and stable and, therefore, did not require more-invasive intervention. The lymphedema slowly improved over time but did not fully resolve. With these interventions, the frequency of the patient’s bronchiectasis exacerbations had dramatically decreased.


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