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Yellow nail syndrome: Report of five cases
Clinical a n d l a b o r a l o r u s t u d i e s III
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Yellow nail syndrome: Report of five cases Pierre Y. Venencie, M.D.,* and Charles H. Dicken, M.D.
Rochester, MN Five patients with the yellow nail syndrome triad are described; all five had yellow nails, primary lyrnphedema, and respiratory tract involvement. Four of the patients noted the onset of the syndrome after an episode of pneumonia. Four patients had a chronic productive cough, two had bronchiectasis, two had chronic sinusitis, and one had chronic pleural effusion. Two of the five had spontaneous improvement of their yellow nails. (J AM ACADDERMATOL 10:187-192, 1984.)
Yellow nails and primary lymphedema were reported by Samman and White in 1964.1 The association of chronic recurrent pleural effusions, bronchiectasis, sinusitis, and other respiratory manifestations is now known to be part of this syndrome, '2-~i and the yellow nail syndrome is best described as a triad of yellow nails, lymphedema, and respiratory tract involvement, but all three features need not be present. :~-~ Herein we report five new cases of the yellow nail syndrome seen at the Mayo Clinic since 1972; the patients had yellow nails, lymphedema, and various types of respiratory tract involvement.
CASE REPORTS Case 1 A 46-year-old man was seen at the Mayo Clinic in October, 1978, because of a yellow discoloration of his nails and bronchiectasis. He had been aware of slow nail growth since an episode of pneumonia in February, 1977. Four months later, a chronic productive cough and mild dyspnea on exertion had developed. He was a nonsmoker. Bronchography done in September, 1978, showed bronchiectasis of the left lower lobe. On physical examination, the distal part of the From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication May 20, 1983. Reprint requests to: Dr. C. H. Dicken, Mayo Clinic, 200 First St., SW, Rochester, MN 55905/507-284-2555. *Visiting clinician from the Clinique Dermatologique (Pr. A. Puissant), H6pital Saint-Louis, Paris, France.
fingernails and the entire toenails were yellow. All of the nails had excessive curvature from side to side, and some transverse ridging, loss of the lunulae and the cuticles, and some onycholysis (Fig. 1). Cultures of his fingernails for fungi and yeast were negative. Inspection and palpation of the lower half of the legs revealed a nonpitting edema that was consistent with lymphedema. Chest roentgenograms showed bronchiectasis of the left lower lobe. No pleural effusion was seen, Pulmonary function tests showed a moderate obstruction and normal diffusion of carbon monoxide. The patient had chronic sinusitis, and sinus roentgenograms showed a bilateral membrane thickening of the antra. An electrocardiogram showed a complete right bundle branch block. Case 2 A 39-year-old man was examined at the Mayo Clinic in August, 1980, because of yellow nails and lymphedema of his legs. He had first noticed a change in the color of his nails, slow nail growth, and swelling of his legs in 1974 after an episode of pneumonia. On physical examination, the distal part of the fingernails and the entire toenails were yellow. The nails (Fig. 2) showed excessive curvature from side to side, thickening, onycholysis, and absence of cuticles and lunulae, and swelling of the fingers was evident, Culture of the right large toenail was negative for fungi and yeast. Lymphedema of the feet, ankles, and legs was present (Fig. 3). There was no pleural effusion, bronchitis, bronchiectasis, or sinusitis on the basis of the history, clinical examination, or roentgenograms. An electrocardiogram was normal. 187
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Fig. 1. Case 1. Distal yellow discoloration of fingernails, with transverse ridging, onycholysis, and loss of lunulae and cuticles. Fig. 2. Case 2. Swelling of fingers, yellow-green discoloration of nails, exaggerated longitudinal and transverse curvature, thickening, onycholysis, and loss of lunulae and cuticles, Fig. 3. Case 2. Lymphedema of legs, ankles, and feet. Fig. 4. Case 3. Yellow toenails.
Case 3 A 66-year-old man was seen at the Mayo Clinic in August, 1978, because of yellow nails, lymphedema, and a chronic productive cough. He had first been aware of nail changes in 1975 after the onset of chronic bronchitis and mild dyspnea with exertion. He had stopped smoking 28 years previously. Swelling of his legs started in June, 1978.
On physical examination, the patient had yellow fingernails and toenails (Fig. 4), thickening of the nails, and absence of the lunulae and cuticles. The fingers were swollen, and three fingernails had been shed. Cultures of his fingernaiIs and toenails were negative for fungi and yeasts. He had lymphedema of the lower part of the legs. The chest roentgenograms showed some nodular densities of the left base, which were inter-
Volume 10 Number 2, Part 1 February, 1984
preted to be the result of a recent infectious episode. The sinus roentgenograms were normal. He was given antibiotics for the bronchitis, and a regimen of vitamin E, 400 IU twice a day, was begun. The patient was reexamined in September, 1981, and he was still taking the same dose of vitamin E. The lymphedema of the legs persisted, and his respiratory symptoms were unchanged. On physical examination, all of the fingernails except the thumbnails were normal. The toenails were yellow, thickened, and crumbly. Culture of the toenails was positive for Trichophyton mentagrophytes. Chest roentgenograms showed bilateral basal bronchiectasis and some areas of atelectasis. No pleural effusion was seen. No sinusitis was evident clinically or radiologically. The pulmonary function tests showed a moderate obstruction and normal diffusion of carbon monoxide. An electrocardiogram was normal. Case 4 A 29-year-old man was first seen at the Mayo Clinic in July, 1976, because of yellow nails and lymphedema of the legs and hands. He had had pneumonia in 1973, and a unilateral pleural effusion had developed in 1975. A pleural biopsy specimen showed chronic fibrous pleuritis. Since 1975, he had had a chronic productive cough and mild dyspnea on exertion. He had first been aware of slow nail growth and a change in the color of the nails in 1974. The onset of the swelling of his legs and hands was in 1976. On physical examination, he had yellow fingernails and toenails and lymphedema of his legs and his hands. Cultures of the fingernails were negative for fungi and yeasts. Chest roentgenograms disclosed bilateral thickening of the pleura. Pulmonary function tests showed a restrictive process with reduction of the diffusion of carbon monoxide and a mild obstruction. No sinusitis was evident clinically or radiologically. An electrocardiograrn was normal. He was given antibiotics for respiratory symptoms and vitamin E, 1,200 IU per day. On telephone follow-up in January, 1983, he stated that he had taken the vitamin E for 1 year and had noted no change in his nails. The pleural effusion and lymphedema were still present; however, during 1982, all of his fingernails and all toenails except the first and second had become normal. Case 5 A 46-year-old man was seen at the Mayo Clinic in May, 1978, because of yellow nails, lymphedema, and chronic productive cough. In 1974, he had had pneu-
Yellow nail syndrome
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T a b l e I. Nail changes that occur in the yellow nail syndrome l'z Slow growth (less than 0.2 mm/wk) Yellow to yellow-green discoloration (total or distal) Overcurvature: transverse and longitudinal Thickening Onycholysis Shedding Cross-ridging Loss of the lunulae Loss of the cuticles
monia of the left lower lobe. Since 1974, he had had repeated upper respiratory infections and bronchorrhea. He was a nonsmoker. The onset of the nail changes was in 1975, and the lymphedema of the lower part of the legs had begun in 1976. On physical examination, the fingernails and toenails were yellow and the thumbnails and the large toenails were thickened. Lymphedema of the lower part of the legs was present. Chest roentgenograms showed the residual infiltrate of a recent infection. No pleural effusion was seen. He had chronic sinusitis, and the sinus roentgenograms showed the opacification of both maxillary antra. An electrocardiogram was normal. His respiratory infections were treated with antibiotics. In 1982, his clinical findings were unchanged. Pulmonary function studies showed a mild obstruction and normal diffusion of carbon monoxide. L a b o r a t o r y studies The erythrocyte sedimentation rate was slightly elevated in Patients 2, 3, and 5. In all patients, the following tests were normal or negative: hemoglobin, white blood cell count, leukocyte differential, serum protein electrophoresis, serum immunoglobulins, blood chemistry, calcium, creatinine, thyroxine, syphilis serology, liver function tests, and urinalysis. DISCUSSION The yellow color and the various deformities 1'7 of the nails, such as those seen in our patients and listed in Table I, are characteristic o f the yellow nail syndrome. Usually, these nail changes prompt the patient to consult a dermatologist. In none of these patients could the yellowish discoloration be related to previous tetracycline treatment, s This finding of T. mentagrophytes in the toenails o f the third patient during his follow-up is considered to
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Table II. Summary of the symptoms in five male patients with yellow nail syndrome (with age of discovery in years)
Initial event Yellow nails* Lymphedema
t
Chronic productive cough Bronchiectasis Pleural effusion
[ ......Ca~ No. 1
2
Pneumonia 45 46 (legs) 45 Left lower lobe --
Pneumonia 34 34 (hands, legs) ----
Moderate obstruction, normal carbon monoxkle diffusion
Pulmonary function test
Sinusitis
Chronic 1
Follow-up'~
Not done
63 66 (face, hands, legs) 63 Bilateral basal --
Moderate obstruction, normal carbon monoxide diffi~sion
--
5
6 (partial improvement with vitamin E)
* Fingernails and toenails in all patients. tSince the onset of symptoms, in years.
Table III. Nonrespiratory features reported in patients with the yellow nail syndrome HypothyroidismTM Hashimoto' s thyroiditis 4 Thyrotoxicosis~5 Nephrotic syndromeTM Persistent hypoalbuminemiaTM Macroglobulinemia17 Hypogammaglobulinemialo Complete absence of IgA1~
Decreased levels of IgMTM LymphopeniaTM Malignant lesion~,1~ Rheumatoid arthritis"0,zl* Raynaud's disease~2 Unequal breasts 2z Mental retardations Coronary insufficiency1,24 Unilateral kidney hypoplasia a Malabsorption -- ascites r
* Patient was receiving o-penicillamine.
represent a superinfection phenomenon. When the nail changes are recognized as suggestive of the yellow nail syndrome, then physical examination is indicated to search for lymphedema. The lymphedema was slight in four of our patients (cases 1, 2, 4, and 5) and could easily have been overlooked. In some cases, such as in Case 3, the lymphedema may be severe and may involve the face. 1,z Impaired lymph drainage is thought to be the
underlying defect responsible for the various clinical findings in patients with the yellow nail syndrome, t.2,.,~,t0The reason for the wide range in age and type of onset may be that it takes extra stress on the lymphatic system (such as infection, hypostasis, insect bite, or injury) to increase local capillary permeability and to increase the load on the already deficient lymphatics that are unable to drain off sufficient protein, and edema occurs and persists. Infection in the form of an episode of pneumonia was the first manifestation of the disease in four of our five patients (Cases 1, 3, 4, and 5). Other respiratory manifestations such as sinusitis (Case 2), bronchitis (Case 4), and bronchiectasis (Case 1) were common (Table II), and these types of respiratory tract involvements have been noted in other reported cases. '-'~,~-lz The first patient with pleural effusion was described by Emerson 3 in 1966, two years after Sarnman and White's 1 original report of this syndrome. Pleural effusion was present in our Case 4. Defective lymph drainage tl in the nail regions is also thought to be the cause of the slow nail growth and the development of the thickened yellow nails and other nail changes listed in Table I.
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Yellow nail syndrome
Case No. 4
Pneumonia 1 yr before 26 28 (hands, legs) 28 28 (unilateral) Restriction with proportionally diminished carbon monoxkle diffusion, moderate obstruction -8 (spontaneous partial improvement)
,
5
Pneumonia 43 44 (legs) 42
Moderate obstruction, normal carbon monoxide diffusion Chronic 10
Our patients ranged in age fi'om 26 to 63 years at onset of the syndrome; this wide range in age is typical of other reported cases.J'7 Although our patients were male, the literature suggests an equal distribution of male and female patients. ~,r The family history was negative in all of our cases but a familial case of the yellow nail syndrome has been reported, 1'~ and it has been reported in patients with a family history of congenital lymphedema ~4 or of primary lymphedema of late onset, a'9,15 None of the nonrespiratory association previously reported (Table III) in patients with the yellow nail syndrome was found in our patients. The question of a relationship to a malignant process or to immunologic deficiencies has been raised in previous reports, but this question remains unanswered. None of our patients had a malignant lesion or an immunologic deficiency. Spontaneous improvement of the nails has occurred in about a third of the reported c a s e s : Two of our patients experienced nail improvement. Ayres and Mihan 2.~ reported one case in which improvement was noted with vitamin E therapy. One of our patients (Case 3) had improvement while taking vitamin E. One patient (Case 5) took vitamin E for 1 year and did not have improve-
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ment during that time but experienced improvement 3 years after discontinuing the use of vitamin E. It is impossible to determine whether the vitamin E was of any benefit or the improvement was spontaneous and would have occurred anyway. Samman and Abel126 reported complete recovery of normal nail growth in some or all nails in five of ten patients treated with intradermal injections of triamcinolone acetonide. This type of therapy was not attempted in any of our patients, These cases illustrate well the triad of yellow nails, primary lymphedema, and respiratory tract involvement, The range of respiratory tract involvement indicates the need for a careful evaluation of the respiratory system in patients with the yellow nail syndrome. REFERENCES
1. Samman PD, White WF: The "yellow nail" syndrome. Br J Dermatol 76:153-157, 1964. 2. Zerl:as AJ: Yellow nail syndrome with bilateral bronehieetasis. Proc R Soc Med 59:44, 1965, 3. Emerson PA: Yellow nails, lymphoedema, and pleural effusions. Thorax 21:247-253, 1966. 4. Dilley JJ, Kierland RR, Randall RV, Shick RM; Primary lymphedema associated with yellow nails and pleurat effusions. JAMA 204:670-673, 1968. 5. Hiller E, RosenowEC III, Olsen AM: Pulmonarymanifestations of the yellow nail syndrome. Chest 61:452458, 1972. 6. Beer DJ, Pereira W Jr, Snider GL: Pleural effusion associated with primary lymphedema: A perspectiveon the yellow nail syndrome. Am Rev Respir Dis 117:595-599, 1978. 7. Samman PD: The yellow nail syndrome (report on 55 cases). Trans St. Johns Hosp Dermatol Soc 59:37-38, 1973. 8. Baran R: Pigmentations of the nails (chromonychia). J Dermatol Surg Oncol 4:250-254, 1978. 9. Marks R, Ellis JP: Yellow nails. A report of six cases. Arch Dermatol 102:619-623, 1970. 10. RunyonBA, ForkerEL, SopkoJA: Pleural-fluidkinetics in a patient with primary lymphedema, pleural effusions, and yellow nails. Am Rev Respir Dis 119:821-825, 1979. 11. Barriere H, Litoux P, Berger M, et al: Syndrome des ongles jaunes. Ann Dermatol Venereol (Paris) 107: 677-680, 1980. 12. Nakielna EM, Wilson J, Ballon HS: Yellow-nail syndrome: Report of three cases. Can Med Assoc J 115:4648, 1976. 13. Kamatani M, Rai A, Hen H, et al: Yellownail syndrome associated with mental retardation in two siblings. Br J Dermatol 99:329-333, 1978. 14. Siegelman SS, Heckman BH, Hasson J: Lymphedema, pleural effusions and yellow nails. Associated immunologic deficiency. Chest 56:114-117, 1969.
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15. Wells GC: Yellow nail syndrome: With familial primary hypoplasia of lymphatics, manifest late in life, Proc R Sac Med 59:447, 1966. 16. Cock.ram CS, Richard PR: Yellow nails and nephrotic syndrome. Br J Dermatol 101:707-709, 1979. 17. D'Souza MF: Generalized lymphaedema with yellow nails, pleural effusions and macroglobulinaemia. Proc R Sac IVied 63:456, 1970. 18, Lubach D, Stolte H: Yellow-nail-syndrom. Med Klin 74:1291-1294, 1979. 19. Guin JD, Elleman JH: Yellow nail syndrome, Possible association with malignancy, Arch Dermatol 115:734735, 1979, 20, Mattingly PC, Bossingham DH: Yellow nail syndrome in rheumatoid arthritis: Report of three cases, Ann Rheum Dis 38:475-478, 1979.
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21. Lubach D, Margheseu S; Yellow-nail-syndrom dutch d-Penizillamin. Hautarzt 30:547-549, 1979. 22. Awerbuch MS: The yellow nail syndrome, bronchiectasis and Raynaud's disease--a relationship. Med J Aust 2:829-830, 1976. 23. Bowers D: Unequal breasts, yellow nails, bronchiectasis and lymphedema, Can Med Assoc J 100:437-438, 1969, 24. Scott J: Cardiac infarction and yellow nail syndrome, Proc R Sac Med 67:323, 1974. 25. Ayres S Jr, Mihan R: Yellow nail syndrome, Response to vitamin E. Arch Dcrmatol 108:267-268, 1973, 26. Samman PD, Abe[l E: lntradennal triamcinolone aeeto. nide injection in the yellow nail syndrome. Trans St, Johns Hasp Dennatol Sac 59:1 14-117, 1973.
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Hereditary hemorrhagic telangiectasia versus CREST syndrome: Can serology aid diagnosis? Marvin J. Fritzler, Ph.D., M,D,, *,** Jolm P. Arlette, M .D, ,*** Alan R. Behm, M.D. ,*** and T. Douglas Kinsella, M.D.*,**** Calgary, AIberta, Cana~kl Because the telangiectasia of hereditary hemorrhagic telangiectasia (HHT) and the CREST variant of scleroderma may be indistinguishable, we have tested the sera of eight patients with HHT for the presence of antinuclear (ANA) and anticentromere antibodies (ACA). In contrast to patients with the CREST syndrome, none of the sera of patients with HI-IT had elevated levels of ANA and a search for ACA was negative. Therefore, the presence of ACA may help differentiate the patient with CREST from the patient with HHT. (J AM ACAD DERMATOL10:192-196, 1984.)
The CREST variant of scleroderma (ThibiergeWeissenbach syndrome) ~,2 shares the common clinical feature of prominent telangiectasia with
From the Departments of Medicine* and Medical Biochemistry,** the Division of Dermatology,*** and The Rheumatic Diseases Unit,**** University of Calgary. Supported by the Medical Research Council of Canada, Accepted for publication May 25, 1983. Reprint requests to: Dr. M, J. Fritzler, Department of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta T2N 4N1/403-284-6867.
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hereditary hemorrhagic telangiectasia (HHT) of Osler-Rendu-Weber. :~ The clinical appearance of the cutaneous vascular lesions in these two disorders can be so similar that it is difficult to distinguish one disorder from the other. 4-~ A comprehensive description of skin lesions that resemble HHT and the telangiectasia of CREST has been reviewed by Bean. r It is well known that one feature of the CREST syndrome m a y antedate the others by up to 15 years. Thus, when the features of calcinosis, Raynaud's phenomenon, esophageal dysfunction, or sclerodactyly are absent in early, or
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Yellow nail syndrome: Report of five cases Pierre Y. Venencie, M.D.,* and Charles H. Dicken, M.D.
Rochester, MN Five patients with the yellow nail syndrome triad are described; all five had yellow nails, primary lyrnphedema, and respiratory tract involvement. Four of the patients noted the onset of the syndrome after an episode of pneumonia. Four patients had a chronic productive cough, two had bronchiectasis, two had chronic sinusitis, and one had chronic pleural effusion. Two of the five had spontaneous improvement of their yellow nails. (J AM ACADDERMATOL 10:187-192, 1984.)
Yellow nails and primary lymphedema were reported by Samman and White in 1964.1 The association of chronic recurrent pleural effusions, bronchiectasis, sinusitis, and other respiratory manifestations is now known to be part of this syndrome, '2-~i and the yellow nail syndrome is best described as a triad of yellow nails, lymphedema, and respiratory tract involvement, but all three features need not be present. :~-~ Herein we report five new cases of the yellow nail syndrome seen at the Mayo Clinic since 1972; the patients had yellow nails, lymphedema, and various types of respiratory tract involvement.
CASE REPORTS Case 1 A 46-year-old man was seen at the Mayo Clinic in October, 1978, because of a yellow discoloration of his nails and bronchiectasis. He had been aware of slow nail growth since an episode of pneumonia in February, 1977. Four months later, a chronic productive cough and mild dyspnea on exertion had developed. He was a nonsmoker. Bronchography done in September, 1978, showed bronchiectasis of the left lower lobe. On physical examination, the distal part of the From the Department of Dermatology, Mayo Clinic and Mayo Foundation. Accepted for publication May 20, 1983. Reprint requests to: Dr. C. H. Dicken, Mayo Clinic, 200 First St., SW, Rochester, MN 55905/507-284-2555. *Visiting clinician from the Clinique Dermatologique (Pr. A. Puissant), H6pital Saint-Louis, Paris, France.
fingernails and the entire toenails were yellow. All of the nails had excessive curvature from side to side, and some transverse ridging, loss of the lunulae and the cuticles, and some onycholysis (Fig. 1). Cultures of his fingernails for fungi and yeast were negative. Inspection and palpation of the lower half of the legs revealed a nonpitting edema that was consistent with lymphedema. Chest roentgenograms showed bronchiectasis of the left lower lobe. No pleural effusion was seen, Pulmonary function tests showed a moderate obstruction and normal diffusion of carbon monoxide. The patient had chronic sinusitis, and sinus roentgenograms showed a bilateral membrane thickening of the antra. An electrocardiogram showed a complete right bundle branch block. Case 2 A 39-year-old man was examined at the Mayo Clinic in August, 1980, because of yellow nails and lymphedema of his legs. He had first noticed a change in the color of his nails, slow nail growth, and swelling of his legs in 1974 after an episode of pneumonia. On physical examination, the distal part of the fingernails and the entire toenails were yellow. The nails (Fig. 2) showed excessive curvature from side to side, thickening, onycholysis, and absence of cuticles and lunulae, and swelling of the fingers was evident, Culture of the right large toenail was negative for fungi and yeast. Lymphedema of the feet, ankles, and legs was present (Fig. 3). There was no pleural effusion, bronchitis, bronchiectasis, or sinusitis on the basis of the history, clinical examination, or roentgenograms. An electrocardiogram was normal. 187
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Fig. 1. Case 1. Distal yellow discoloration of fingernails, with transverse ridging, onycholysis, and loss of lunulae and cuticles. Fig. 2. Case 2. Swelling of fingers, yellow-green discoloration of nails, exaggerated longitudinal and transverse curvature, thickening, onycholysis, and loss of lunulae and cuticles, Fig. 3. Case 2. Lymphedema of legs, ankles, and feet. Fig. 4. Case 3. Yellow toenails.
Case 3 A 66-year-old man was seen at the Mayo Clinic in August, 1978, because of yellow nails, lymphedema, and a chronic productive cough. He had first been aware of nail changes in 1975 after the onset of chronic bronchitis and mild dyspnea with exertion. He had stopped smoking 28 years previously. Swelling of his legs started in June, 1978.
On physical examination, the patient had yellow fingernails and toenails (Fig. 4), thickening of the nails, and absence of the lunulae and cuticles. The fingers were swollen, and three fingernails had been shed. Cultures of his fingernaiIs and toenails were negative for fungi and yeasts. He had lymphedema of the lower part of the legs. The chest roentgenograms showed some nodular densities of the left base, which were inter-
Volume 10 Number 2, Part 1 February, 1984
preted to be the result of a recent infectious episode. The sinus roentgenograms were normal. He was given antibiotics for the bronchitis, and a regimen of vitamin E, 400 IU twice a day, was begun. The patient was reexamined in September, 1981, and he was still taking the same dose of vitamin E. The lymphedema of the legs persisted, and his respiratory symptoms were unchanged. On physical examination, all of the fingernails except the thumbnails were normal. The toenails were yellow, thickened, and crumbly. Culture of the toenails was positive for Trichophyton mentagrophytes. Chest roentgenograms showed bilateral basal bronchiectasis and some areas of atelectasis. No pleural effusion was seen. No sinusitis was evident clinically or radiologically. The pulmonary function tests showed a moderate obstruction and normal diffusion of carbon monoxide. An electrocardiogram was normal. Case 4 A 29-year-old man was first seen at the Mayo Clinic in July, 1976, because of yellow nails and lymphedema of the legs and hands. He had had pneumonia in 1973, and a unilateral pleural effusion had developed in 1975. A pleural biopsy specimen showed chronic fibrous pleuritis. Since 1975, he had had a chronic productive cough and mild dyspnea on exertion. He had first been aware of slow nail growth and a change in the color of the nails in 1974. The onset of the swelling of his legs and hands was in 1976. On physical examination, he had yellow fingernails and toenails and lymphedema of his legs and his hands. Cultures of the fingernails were negative for fungi and yeasts. Chest roentgenograms disclosed bilateral thickening of the pleura. Pulmonary function tests showed a restrictive process with reduction of the diffusion of carbon monoxide and a mild obstruction. No sinusitis was evident clinically or radiologically. An electrocardiograrn was normal. He was given antibiotics for respiratory symptoms and vitamin E, 1,200 IU per day. On telephone follow-up in January, 1983, he stated that he had taken the vitamin E for 1 year and had noted no change in his nails. The pleural effusion and lymphedema were still present; however, during 1982, all of his fingernails and all toenails except the first and second had become normal. Case 5 A 46-year-old man was seen at the Mayo Clinic in May, 1978, because of yellow nails, lymphedema, and chronic productive cough. In 1974, he had had pneu-
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T a b l e I. Nail changes that occur in the yellow nail syndrome l'z Slow growth (less than 0.2 mm/wk) Yellow to yellow-green discoloration (total or distal) Overcurvature: transverse and longitudinal Thickening Onycholysis Shedding Cross-ridging Loss of the lunulae Loss of the cuticles
monia of the left lower lobe. Since 1974, he had had repeated upper respiratory infections and bronchorrhea. He was a nonsmoker. The onset of the nail changes was in 1975, and the lymphedema of the lower part of the legs had begun in 1976. On physical examination, the fingernails and toenails were yellow and the thumbnails and the large toenails were thickened. Lymphedema of the lower part of the legs was present. Chest roentgenograms showed the residual infiltrate of a recent infection. No pleural effusion was seen. He had chronic sinusitis, and the sinus roentgenograms showed the opacification of both maxillary antra. An electrocardiogram was normal. His respiratory infections were treated with antibiotics. In 1982, his clinical findings were unchanged. Pulmonary function studies showed a mild obstruction and normal diffusion of carbon monoxide. L a b o r a t o r y studies The erythrocyte sedimentation rate was slightly elevated in Patients 2, 3, and 5. In all patients, the following tests were normal or negative: hemoglobin, white blood cell count, leukocyte differential, serum protein electrophoresis, serum immunoglobulins, blood chemistry, calcium, creatinine, thyroxine, syphilis serology, liver function tests, and urinalysis. DISCUSSION The yellow color and the various deformities 1'7 of the nails, such as those seen in our patients and listed in Table I, are characteristic o f the yellow nail syndrome. Usually, these nail changes prompt the patient to consult a dermatologist. In none of these patients could the yellowish discoloration be related to previous tetracycline treatment, s This finding of T. mentagrophytes in the toenails o f the third patient during his follow-up is considered to
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Venencie andDicken
Table II. Summary of the symptoms in five male patients with yellow nail syndrome (with age of discovery in years)
Initial event Yellow nails* Lymphedema
t
Chronic productive cough Bronchiectasis Pleural effusion
[ ......Ca~ No. 1
2
Pneumonia 45 46 (legs) 45 Left lower lobe --
Pneumonia 34 34 (hands, legs) ----
Moderate obstruction, normal carbon monoxkle diffusion
Pulmonary function test
Sinusitis
Chronic 1
Follow-up'~
Not done
63 66 (face, hands, legs) 63 Bilateral basal --
Moderate obstruction, normal carbon monoxide diffi~sion
--
5
6 (partial improvement with vitamin E)
* Fingernails and toenails in all patients. tSince the onset of symptoms, in years.
Table III. Nonrespiratory features reported in patients with the yellow nail syndrome HypothyroidismTM Hashimoto' s thyroiditis 4 Thyrotoxicosis~5 Nephrotic syndromeTM Persistent hypoalbuminemiaTM Macroglobulinemia17 Hypogammaglobulinemialo Complete absence of IgA1~
Decreased levels of IgMTM LymphopeniaTM Malignant lesion~,1~ Rheumatoid arthritis"0,zl* Raynaud's disease~2 Unequal breasts 2z Mental retardations Coronary insufficiency1,24 Unilateral kidney hypoplasia a Malabsorption -- ascites r
* Patient was receiving o-penicillamine.
represent a superinfection phenomenon. When the nail changes are recognized as suggestive of the yellow nail syndrome, then physical examination is indicated to search for lymphedema. The lymphedema was slight in four of our patients (cases 1, 2, 4, and 5) and could easily have been overlooked. In some cases, such as in Case 3, the lymphedema may be severe and may involve the face. 1,z Impaired lymph drainage is thought to be the
underlying defect responsible for the various clinical findings in patients with the yellow nail syndrome, t.2,.,~,t0The reason for the wide range in age and type of onset may be that it takes extra stress on the lymphatic system (such as infection, hypostasis, insect bite, or injury) to increase local capillary permeability and to increase the load on the already deficient lymphatics that are unable to drain off sufficient protein, and edema occurs and persists. Infection in the form of an episode of pneumonia was the first manifestation of the disease in four of our five patients (Cases 1, 3, 4, and 5). Other respiratory manifestations such as sinusitis (Case 2), bronchitis (Case 4), and bronchiectasis (Case 1) were common (Table II), and these types of respiratory tract involvements have been noted in other reported cases. '-'~,~-lz The first patient with pleural effusion was described by Emerson 3 in 1966, two years after Sarnman and White's 1 original report of this syndrome. Pleural effusion was present in our Case 4. Defective lymph drainage tl in the nail regions is also thought to be the cause of the slow nail growth and the development of the thickened yellow nails and other nail changes listed in Table I.
Volume 10 Number 2, Pa:~ 1 February, 1984
Yellow nail syndrome
Case No. 4
Pneumonia 1 yr before 26 28 (hands, legs) 28 28 (unilateral) Restriction with proportionally diminished carbon monoxkle diffusion, moderate obstruction -8 (spontaneous partial improvement)
,
5
Pneumonia 43 44 (legs) 42
Moderate obstruction, normal carbon monoxide diffusion Chronic 10
Our patients ranged in age fi'om 26 to 63 years at onset of the syndrome; this wide range in age is typical of other reported cases.J'7 Although our patients were male, the literature suggests an equal distribution of male and female patients. ~,r The family history was negative in all of our cases but a familial case of the yellow nail syndrome has been reported, 1'~ and it has been reported in patients with a family history of congenital lymphedema ~4 or of primary lymphedema of late onset, a'9,15 None of the nonrespiratory association previously reported (Table III) in patients with the yellow nail syndrome was found in our patients. The question of a relationship to a malignant process or to immunologic deficiencies has been raised in previous reports, but this question remains unanswered. None of our patients had a malignant lesion or an immunologic deficiency. Spontaneous improvement of the nails has occurred in about a third of the reported c a s e s : Two of our patients experienced nail improvement. Ayres and Mihan 2.~ reported one case in which improvement was noted with vitamin E therapy. One of our patients (Case 3) had improvement while taking vitamin E. One patient (Case 5) took vitamin E for 1 year and did not have improve-
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ment during that time but experienced improvement 3 years after discontinuing the use of vitamin E. It is impossible to determine whether the vitamin E was of any benefit or the improvement was spontaneous and would have occurred anyway. Samman and Abel126 reported complete recovery of normal nail growth in some or all nails in five of ten patients treated with intradermal injections of triamcinolone acetonide. This type of therapy was not attempted in any of our patients, These cases illustrate well the triad of yellow nails, primary lymphedema, and respiratory tract involvement, The range of respiratory tract involvement indicates the need for a careful evaluation of the respiratory system in patients with the yellow nail syndrome. REFERENCES
1. Samman PD, White WF: The "yellow nail" syndrome. Br J Dermatol 76:153-157, 1964. 2. Zerl:as AJ: Yellow nail syndrome with bilateral bronehieetasis. Proc R Soc Med 59:44, 1965, 3. Emerson PA: Yellow nails, lymphoedema, and pleural effusions. Thorax 21:247-253, 1966. 4. Dilley JJ, Kierland RR, Randall RV, Shick RM; Primary lymphedema associated with yellow nails and pleurat effusions. JAMA 204:670-673, 1968. 5. Hiller E, RosenowEC III, Olsen AM: Pulmonarymanifestations of the yellow nail syndrome. Chest 61:452458, 1972. 6. Beer DJ, Pereira W Jr, Snider GL: Pleural effusion associated with primary lymphedema: A perspectiveon the yellow nail syndrome. Am Rev Respir Dis 117:595-599, 1978. 7. Samman PD: The yellow nail syndrome (report on 55 cases). Trans St. Johns Hosp Dermatol Soc 59:37-38, 1973. 8. Baran R: Pigmentations of the nails (chromonychia). J Dermatol Surg Oncol 4:250-254, 1978. 9. Marks R, Ellis JP: Yellow nails. A report of six cases. Arch Dermatol 102:619-623, 1970. 10. RunyonBA, ForkerEL, SopkoJA: Pleural-fluidkinetics in a patient with primary lymphedema, pleural effusions, and yellow nails. Am Rev Respir Dis 119:821-825, 1979. 11. Barriere H, Litoux P, Berger M, et al: Syndrome des ongles jaunes. Ann Dermatol Venereol (Paris) 107: 677-680, 1980. 12. Nakielna EM, Wilson J, Ballon HS: Yellow-nail syndrome: Report of three cases. Can Med Assoc J 115:4648, 1976. 13. Kamatani M, Rai A, Hen H, et al: Yellownail syndrome associated with mental retardation in two siblings. Br J Dermatol 99:329-333, 1978. 14. Siegelman SS, Heckman BH, Hasson J: Lymphedema, pleural effusions and yellow nails. Associated immunologic deficiency. Chest 56:114-117, 1969.
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15. Wells GC: Yellow nail syndrome: With familial primary hypoplasia of lymphatics, manifest late in life, Proc R Sac Med 59:447, 1966. 16. Cock.ram CS, Richard PR: Yellow nails and nephrotic syndrome. Br J Dermatol 101:707-709, 1979. 17. D'Souza MF: Generalized lymphaedema with yellow nails, pleural effusions and macroglobulinaemia. Proc R Sac IVied 63:456, 1970. 18, Lubach D, Stolte H: Yellow-nail-syndrom. Med Klin 74:1291-1294, 1979. 19. Guin JD, Elleman JH: Yellow nail syndrome, Possible association with malignancy, Arch Dermatol 115:734735, 1979, 20, Mattingly PC, Bossingham DH: Yellow nail syndrome in rheumatoid arthritis: Report of three cases, Ann Rheum Dis 38:475-478, 1979.
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21. Lubach D, Margheseu S; Yellow-nail-syndrom dutch d-Penizillamin. Hautarzt 30:547-549, 1979. 22. Awerbuch MS: The yellow nail syndrome, bronchiectasis and Raynaud's disease--a relationship. Med J Aust 2:829-830, 1976. 23. Bowers D: Unequal breasts, yellow nails, bronchiectasis and lymphedema, Can Med Assoc J 100:437-438, 1969, 24. Scott J: Cardiac infarction and yellow nail syndrome, Proc R Sac Med 67:323, 1974. 25. Ayres S Jr, Mihan R: Yellow nail syndrome, Response to vitamin E. Arch Dcrmatol 108:267-268, 1973, 26. Samman PD, Abe[l E: lntradennal triamcinolone aeeto. nide injection in the yellow nail syndrome. Trans St, Johns Hasp Dennatol Sac 59:1 14-117, 1973.
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Hereditary hemorrhagic telangiectasia versus CREST syndrome: Can serology aid diagnosis? Marvin J. Fritzler, Ph.D., M,D,, *,** Jolm P. Arlette, M .D, ,*** Alan R. Behm, M.D. ,*** and T. Douglas Kinsella, M.D.*,**** Calgary, AIberta, Cana~kl Because the telangiectasia of hereditary hemorrhagic telangiectasia (HHT) and the CREST variant of scleroderma may be indistinguishable, we have tested the sera of eight patients with HHT for the presence of antinuclear (ANA) and anticentromere antibodies (ACA). In contrast to patients with the CREST syndrome, none of the sera of patients with HI-IT had elevated levels of ANA and a search for ACA was negative. Therefore, the presence of ACA may help differentiate the patient with CREST from the patient with HHT. (J AM ACAD DERMATOL10:192-196, 1984.)
The CREST variant of scleroderma (ThibiergeWeissenbach syndrome) ~,2 shares the common clinical feature of prominent telangiectasia with
From the Departments of Medicine* and Medical Biochemistry,** the Division of Dermatology,*** and The Rheumatic Diseases Unit,**** University of Calgary. Supported by the Medical Research Council of Canada, Accepted for publication May 25, 1983. Reprint requests to: Dr. M, J. Fritzler, Department of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta T2N 4N1/403-284-6867.
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hereditary hemorrhagic telangiectasia (HHT) of Osler-Rendu-Weber. :~ The clinical appearance of the cutaneous vascular lesions in these two disorders can be so similar that it is difficult to distinguish one disorder from the other. 4-~ A comprehensive description of skin lesions that resemble HHT and the telangiectasia of CREST has been reviewed by Bean. r It is well known that one feature of the CREST syndrome m a y antedate the others by up to 15 years. Thus, when the features of calcinosis, Raynaud's phenomenon, esophageal dysfunction, or sclerodactyly are absent in early, or