versão impressa ISSN 0043-3144
West Indian med. j. vol.60 no.1 Mona jan. 2011
El síndrome de las uñas amarillas en una clínica médica
N IheonunekwuI; O AdedayoI; A ClareII; C CummingsI
IDepartment of Medicine, George Town Hospital, Cayman Islands, West Indies
IIDepartment of Medicine, Dermatology unit, The University of West Indies, Kingston 7, Jamaica, West Indies
Yellow nail syndrome is a very rare clinical entity usually diagnosed from a combination of yellow dystrophic nails, lymphoedema and respiratory diseases. The aetiology is not known though dysfunctional hypoplastic lymphatics is speculated. Most cases occur sporadically but few cases may be associated with systemic diseases or may be inherited. This report documents another case in a 56-year old Caribbean female who presented with a six-year history of recurrent respiratory symptoms and later yellow dystrophic nails and lymphoedema. She responded well to vitamin E and oral fluconazole. We also did a short literature review of yellow nail syndrome.
Keywords: Pleural effusion, lymphoedema, yellow nails
El síndrome de las uñas amarillas es una entidad clínica muy rara, la cual usualmente se diagnostica a partir de una combinación de uñas amarillas distróficas, linfedemas, y enfermedades respiratorias. Se desconoce la etiología, aunque se especula que se debe a vasos linfáticos hipoplásticos disfuncionales. La mayoría de los casos ocurre esporádicamente pero pocos casos pueden asociarse con las enfermedades sistémicas o pueden ser heredados. Este informe documenta el caso de una mujer caribeña de 56 años, que se presentó con antecedentes de síntomas respiratorios recurrentes y más tarde con uñas amarillas distróficas y linfedemas. Durante el tratamiento, respondió bien a la vitamina E y al fluconazol oral. El trabajo también realiza una breve revisión de la literatura del síndrome de las uñas amarillas.
Palabras claves: Efusión pleural, linfedema, uñas amarillas
Yellow nail syndrome (YNS) was initially described by Samman and White in 1964 (1) in patients with a combination of slow growing dystrophic yellow nails and lymphoedema but the association with chronic pleural effusion was later described by Emerson (2).
The diagnosis is mainly clinical with the inclusion of any two: yellow dystrophic nails, lymphoedema or chronic pleural effusion (3) though radio-imaging or lymphatic study with a lymphangiogram may demonstrate hypoplastic lymphatics (1, 4).
Yellow nail syndrome is considered rare with very few cases reported in the literature, however, we describe an additional case in a 56-year old female from the West Indies seen at our medical clinic in George Town Hospital, Cayman Islands.
A 56-year old West Indian female was seen in March 2009 due to a recurrent chronic cough which was productive of yellow purulent sputurm with occasional bloody streaks and recurrent rhinosinusitis that had lasted more than six-years. She had no fever, malaise or significant weight loss. There was no history of contact with persons with pulmonary tuberculosis and she had no history of cigarette smoking.
She developed progressive swelling of both lower limbs which did not resolve with diuretics prescribed on numerous occasions. She had no underlying cardiac, renal or hepatic diseases. She also noticed yellowness of all her nails in the last one-year. Her other medical conditions were diabetes mellitus, hypertension and dyslipidaemia. She had no family history of similar complaints.
On examination, her vitals signs showed: blood pressure of 122/95 mm/Hg, pulse 93 beats/minute, respiratory rate 20 beats/minute and temperature 36.5ºC. She had yellowness and dystrophic changes in all nails (Fig. 1) and bilateral non-pitting pedal oedema (Fig. 2). There was no lymphadenopathy. Her lung examination showed bilateral lower zone crepitations and localized wheeze. Her other systemic examination was unremarkable. Here laboratory findings showed haemoglobin [Hb] 12.5 g/dL, haematocrit [Hct] 38.7%, white cell count 7.98 x 103/mm3, platelets 240 x 103/mm3, serum electrolytes: sodium [Na] 141 mmol/L, potassium [K] 4.2 mmol/L, chloride [Cl] 107 mmol/L, carbon dioxide [C02] 24 mmol/L, blood urea nitrogen [BUN] 5 mg/dL, creatinine [Cr] 0.8 mg/dL, blood glucose 133 mg/dL, alkaline phosphatase [AP] 148 µ/L, aspartate transaminase [AST] 24µ/L, alanine transaminase [ALT] 23 µ/L, total protein 7.1 g/L, albumin 3.5 g/L and total IgG 1330 mg/dL [700-1,600], IgM, IgA as well as IgG subclasses were not available.
Her c-ANCA, p-ANCA, hepatitis B, C and HIV serology were negative as well as cystic fibrosis transmembrane conductance regulator [CFTR] gene mutation for cystic fibrosis.
The CT scan of the chest showed bronchopneumonic changes in the right lung as well as the lower zone of the left lung while a previous CT of the sinuses showed opacification of the maxillary, ethmoidal and sphenoidal sinuses with airfluid levels. Lymphangiography for lymphatic circulation of lower extremities was not done. Her sputurm cultures grew at various times Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, Achromobacter xylosoxidans, Alcaligenes faecalis, and Moraxella catarhalis. Her sputum was negative for mycobacterium and fungus repeatedly.
She received different courses of antibiotics for bronchopneumonia as well as Vitamin E 400 mg daily and diflucan 150 mg weekly.
A review at six-months showed that the nails were less dystrophic and yellowness was resolving.
The patient presented with clinical features consistent with "Yellow nail syndrome" as described by previous authors (1, 2, 3, 5). She had yellow dystrophic nails, bilateral lymphoedema, chronic rhinosinusitis and recurrent bronchopneumonia.
In a review of 41 cases of "yellow nail syndrome" by Maldonado et al (5), the median age of presentation was 61 years, male to female ratio was the same, all had yellow nails, 97.5% had respiratory symptoms and lymphoedema occurred in 63% as the first presentation. The main respiratory diseases were pleural effusion in 46%, bronchiectasis in 44%, chronic sinusitis in 41% and recurrent pneumonia in 22% (5). The nail changes in YNS is best described as slow growing nails with yellowish discoloration, excessive curvature, onycholysis, nail ridging and thickening (1, 5).
The exact aetiopathogenesis of YNS is not known. There are few reported familiar cases (6, 7) but most cases occur sporadically and are either idiopathic or associated with specific systemic diseases such as xanthogranulomatous pyelonephritis (8), malignancy (9), rheumatoid arthritis (10), acquired immune deficiency syndrome (11) and tuberculosis (12).
The index patient did not have a family history ofYNS but she is diabetic. The suggested underlying defect in YNS may be an anatomical or functional disorder of the lymphatic system resulting in compromised drainage of the lymphatics (4, 5). In the series of 12 patients by Bull et al (4), four had lymphangiography and all demonstrated lymphatic hypoplasia.
Failure of development of large lymphatics may cause stasis and dilation of smaller lymphatic capillaries resulting in fluid exudation.
The role of immunologic deficiency in YNS is not clear. There are case reports of functional and quantitative immunoglobulin deficiency. Bokszczanin and Levinson (13) reported a case with recurrent upper and lower respiratory tract infection with impaired IgG antibody response to polysacharride antigens despite a normal total IgG, IgA, IgM, while other patients were reported with hypogammaglobulinemia (14, 15).
The total IgG was normal in the index case, however IgG subclass, IgM, IgA as well as antigenic response to antigens as pneumovax or H influenza B vaccine were not available.
Our patient grew Streptococcus pneumonia, Moraxella cattarhalis, Burkholderia cephacia and repeatedly Alcaligenes spp mainly Achromobacter xylosoxidans and Alcaligenes faecalis in her sputurm. B cephacia, A xylosoxidans, A faecalis are gram negative rods found in soil and water, however they are associated with recurrent lung infections in cystic fibrosis patients and are pathogenic in immunosupressed patients.
The other findings documented in patients with YNS may include chylous ascites and intestinal lymphangiectasia (16, 17), chronic chemosis and peri-orbital oedema (18), and severe recurrent pericardial effusion (19).
There is no effective treatment for YNS though some cases may resolve spontaneously. In cases where there is an underlying treateable disease, patients were known to have recovered after satisfactory treatment of the associated systemic diseases (8, 9, 12).
The pleural effusion in YNS may be treated with repeated thoracocentesis or pleurodesis while other respiratory symptoms may benefit from bronchodilators and antibiotics, diuretics or elastic stockings may help in lymphoedema but there is no definitive treatment for nail changes.
Oral vitamin E [alpha-tocopherol] was found beneficial in some cases ofYNS (5, 20). In the case series presented by Maldonado et al (5), five out of eight patients improved significantly with vitamin E treatment but the role of oral azole antifungal is less convincing (21).
The index patient improved with resolution of nail yellowness and dystrophic changes with a combination of oral vitamin E and fluconazole. The combination of pulse therapy with oral azole as fluconazole and vitamin E is very promising. There was complete resolution in 11 out of 13 patients treated with fluconazole and alpha-tocopherol and improvement in the remaining two (22).
Yellow nail syndrome may be a rare clinical syndrome, however the non-occurrence of the triad of nail changes, respiratory symptoms and lymphoedema concurrently in most cases calls for greater vigilance and follow-up when patients present with any of this symptoms.
1. Samman PD, White WF. The "yellow nail syndrome". Br J Dermatol 1964;76:153-7
2. Emerson PA. Yellow nails, lymphoedema, and pleural effusion. Thorax 1966;21:247-53.
3. Hiller E, Rosenow EC 3rd, Olsen AM. Pulmonary manifestations of the Yellow nail syndrome. Chest 1972;61:452-8
4. Bull RH, Fenton DA, Mortimer PS. Lymphatic function in the yellow nail syndrome. Br J Dermatol 1996;134:307-12.
5. Maldonado F, Tazelaar HD, Wang C, Ryu JH. Yellow nail syndrome: analysis of 41 consecutive patients. Chest 2008;134:375-81
6. Razi E. Familiar yellow nail syndrome. Dermatol online J 2006;12:15.
7. Douri T. Yellow nails syndrome in two siblings. Dermatol online J 2008;14:7.
8. Danenberg HD, Eliashar R, Flusser G, Rosenmann E, Chajek-Shaul T. Yellow nail syndrome and xanthogranulomatous pyelonephritis. Postgrad Med J 1995;71:110-1.
9. Igbal M, Rossoff LJ, Marzouk KA, Steinberg HN. Resolution of yellow nails after successful treatment of breast cancer. Chest 2000;117:1516-8.
10. Mattingly PC, Bossingham DH. Yellow nail syndrome in rheumatoid arthritis: report of three cases. Ann Rheum Dis 1979;38:475-8.
11. Chernosky ME, Finley VK. Yellow nail syndrome in patients with acquired immunodeficiency disease. J Am Acad Dermatol 1985;13:731-6.
12. Pang SM. Yellow nail syndrome resolution following treatment of pulmonary Tuberculosis. Int J Dermatol 1993;32:605.
13. Bokszanin A, Levinson AL. Co-existent yellow nails syndrome and selective antibody deficiency. Ann Allergy Asthma Immunol 2003;91:496-500.
14. Lozewicz S, Morris G, Garbett N, Browse N, Slavin B, Cole P. Acquired common variable hypogammaglobulinemia and lymphoedema. Postgrad med J 1988;64:63-5.
15. Siegelman SS, Heckman BH, Hasson J. Lymphedema, Pleural effusions and yellow nails: Associated immunologic deficiency. Dis Chest 1969;56:114-7.
16. Duhra P, Quigley EM, Marsh MN. Chylous ascites, intestinal lymphagiectasia and the "yellow-nail syndrome". Gut 1985;26:1266-9.
17. Malek NP, Ocran K, Tietge UJ et al. A case of the yellow nail syndrome associated with massive chylous ascites, pleural and pericardial effusions. Z Gastroenterol1996;34:763-6.
18. Ayata A, Unal M, Ersanli D, Bilge AH. Ocular findings in yellow nail syndrome. Can J Ophthalmol 2008;43:493-4.
19. Morandi U, Golinelli M, Brandi L, Ruggiero C, Stefani A, Lodi R. "Yellow nail syndrome" associated with chronic recurrent pericardial and pleural effusions. Eur J Cardio-thorac Surg 1995;9:42-4.
20. Pehr K, Forsey R. Why d'ont we use vitamin E in dermatology? Can Med Assoc J 1993;149:1247-53.
21. Tosti A, Piraccini BM, Iorizzo M. Systemic itraconazole in the yellow nail syndrome. Br J Dermatol 2002;146:1064-7.
22. Baran R, Thomas L. Combination of fluconazole and alpha-tocopherol in the treatment of yellow nail syndrome. Drugs Dermatol 2009;8:276-8.
Dr N Iheonunekwu
George Town Hospital