Resolution of Dyshidrotic Dermatitis of the Hand After Treatment with Continuous Positive Airway Pressure for Obstructive Sleep Apnea.

ABSTRACT: Eczema of the palm and obstructive sleep apnea (OSA) are common disorders. Proinflammatory cytokines and cell adhesion molecules are elevated in both of these disorders. We describe an unusual patient with OSA who had recurrent free remission of dermatitis after treatment with continuous positive airway pressure. We speculate that the resolution of the patient's skin condition may reflect the effects of increased tissue oxygenation during sleep, reduced sleep fragmentation, and/or a reduction in sympathetic tone associated with successful sleep apnea treatment.

Nocturnal Hypoxemia is a well-recognized phenomenon in severe obstructive sleep apnea (OSA). Tissue hypoxia has been shown to induce proinflammatory cytokines, adhesion molecules, and tissue inflammation,(1) and sleep apnea may be characterized by elevated cytokines.(2) Dyshidrotic dermatitis is a common form of eczema of the palms and soles. It is of obscure etiology,(3) but like hypoxia, it may also involve cytokines and cell adhesion molecules for induction and maintenance of skin inflammation.(4,5) Continuous positive airway pressure (CPAP) reduces the nocturnal hypoxemia of OSA and could conceivably play a role in reduction of inflammation by reducing circulating cytokines and cell adhesion molecules.

CASE REPORT

A 62-year-old white man was referred in January 1999 for evaluation of loud snoring, pauses in breathing during sleep, and severe daytime sleepiness. These symptoms had existed for more than 10 years. His medical history included dyshidrotic dermatitis in both palms. In March 1998, he had sudden onset of crops of deep-seated vesicles on the palms, first on the right hand and then on the left. He subsequently had recurrent attacks of dermatitis with hyperkeratotic lesions on both palms. He gave no history of exposure to a noxious substance and no history of allergies. In June 1998, a skin biopsy from both palms yeilded microscopic findings of compact orthokeratosis with entrapped serum and transepidermal eliminated Langerhans' cell microabcesses (ie, small collections of Langerhans' cells), irregular epidermal hyperplasia, and a perivascular inflammatory infiltrate of lymphocytes, which were consistent with the diagnosis of dyshidrotic dermatitis. Special stains for fungi were negative. He was treated with multiple courses of topical and oral steroids, without relief.

The patient weighed 261 pounds and was 5 feet 10 inches tall. Skin examination of both palms showed rough hyperkeratotic lesions with multiple deep fissures and confluent vesicles on both palms. He had difficulty using his hands because of pain and swelling.

Results of an overnight polysomnogram in January 1999 showed 78 episodes of obstructive and mixed apnea, 11 episodes of central apnea, and 74 episodes of hypopnea, yielding a respiratory disturbance index (RDI) of 116. The nadir of arterial oxygen saturation ([Sao.sup.2]) was 56%, with a mean of 81%. The arousal index was 94.9, indicating severe sleep fragmentation. During the second portion of the sleep study, nasal CPAP was titrated to an optimal pressure of 17 cm [H.sup.2]O, which reduced the RDI to 24.8, raised the low [Sao.sup.2] to 82% and mean [Sao.sup.2] to 95%, and reduced the arousal index to 10.6. He had consolidated sleep with 12.5% stages 3 and 4 and 7.8% REM sleep, compared with an absence of these stages in the pretitration portion of the study. He was sent home with nasal GPAP at the same pressure.

He was closely monitored via telephone to maintain optimal compliance. He reported use of CPAP for 6 to i hours every night. Eight weeks after initiating CPAP, he noticed that the skin lesions on both hands had improved significantly. At the time, he was not being treated for the dermatitis. On examination in the clinic, the skin on both palms looked less rough, there were no vesicles, and the fissures were well healed. There was no pain or swelling. He was able to play the piano again. He also reported a substantial reduction in daytime sleepiness and nocturnal snoring. This was the first time he had had such improvement in his skin disease.

DISCUSSION

Eczema is a pattern of inflammatory response of the skin with a perivascular infiltrate of lymphocytes around upper dermal vessels, associated with spongiosis and varying degrees of acanthosis. (6) The alternative name is palm dyshidrotic eczema, (pompholyx) reflecting a supposed connection with sweat gland activity. The exact cause of this disease remains unknown, but the role of persistent inflammation and proliferation of kerationcytes and endothelial cells is well defined.(5) The clinical course of this disorder can vary from a mild benign disease of short duration and spontaneous remission to a disabling and disfiguring disorder that is persistent and recalcitrant to therapy, as described in our case. (7)

Sleep apnea may contribute to this condition by several mechanisms. First, patients with OSA have been found to have elevated levels of nitric oxide,(8) which may enhance release of proinflammatory cytokines like tumor necrosis factor [alpha] (TNF-[alpha]) and interleukin 1. It is also known that tissue hypoxia increases the intracellular adhesion molecule 1, E-selectin, (1) and alterations in cell adhesion molecules and cytokines may be involved in the pathogenesis of dermatitis.(9) Alternatively, the phenomenon observed here may reflect sleep loss per se. In rats, extensive and exhaustive sleep deprivation has been associated with development of hyperkeratotic skin lesions in the tail, which initially appeared as small erythematous regions.(10) The mechanism underlying these changes in the rat was unclear; it did not appear to involve protein malnutrition or reduced rates of epidermic mitosis, but it may have been associated with immunosuppression or secondary effects due to autonomic activation. (11,12) Whatever the basis for the observed effects in the rat, our speculation is that CPAP in our patient improved the eczema by decreasing circulating inflammatory factors and enhancing tissue healing with good tissue oxygenation and better sleep. We believe this is the first reported case in which CPAP therapy for sleep apnea was effective in the treatment of skin lesions.

Acknowledgments. We thank Andrew B. Kanik, MD, for performing the pathologic studies.

From the Department of Neurology, Sleep Disorders Center, Emory University School of Medicine, and Sleep Sciences Inc. Atlanta, Ga.

Reprint requests to Donald L. Bliwise, PhD, Emory University School of Medicine, Sleep Disorders Center, WMRB 6000, Atlanta, GA 30322.

References

(1.) Dore-Duffy P, Balabanov R, Beaumont T, et al: Endothelial activation following prolonged hypobaric hypoxia. Microvasc] Res 1999;57:75-85

(2.) Entzian P, Linnemann K, Schlaak M, et al: Obstructive sleep apnea syndrome and circadian rhythm of hormones and cytokines. Am J Respir Crit Care Med 1996;153:1080-1086

(3.) Agrup C: Hand eczema with other dermatoses in south Sweden. Acla Dern Venereol 1969;49 (suppl);61

(4.) Kondo S, Sauder DN: Tumor necrosis factor (TNF) receptor type 1 (p55) is a main mediator for TNF-alpha-induced skin inflammation. Eur J Immunol 1997; 27:1 713-1718

(5.) Sweet WL, Smoller BR: Differential proliferation of endothelial cells and keratinocytes in psoriasis and spongiotic dermatitis. Culan Pathol 1997; 24:356-363

(6.) Ackerman AB, Ragaz A: A plea to expunge the word "eczema from the lexicon of dermatology and dermatopathology. Arch Dermalol Res 1982; 272:407-420

(7.) Arnold HL, Odom RB, James WD: Pompholyx, recalcitrant palmoplantar eruptions. Andrew's Disease of the Skin: Clinical Dennatology. Philadelphia, WB Saunders Co, 8th Ed, 1990, pp 214-229

(8.) Olopade CO, Christon JA, Zakkar M, et al: Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea. Chest 1997;111:1500-1504

(9.) Das PK, De Boer OJ, Visser A, et al: Differential expression of ICAM-1, E-selectin and VCAM-1 by endothelial cells in psoriasis and contact dermatitis. Acta Derm Venereal Suppl (Stokh) 1994; 186:21-22

(10.) Kushida CA, Everson CA, Suthipinittharm P, et al: Sleep deprivation in the rat: VI. Skin changes. Sleep 1989;12;42-46

(11.) Benca RM, Qunitas J: Sleep and host defenses: a review. sleep 1997; 20:1027-1037

(12.) Everson CA: Sustained sleep deprivation impairs host defense. Am J Physiol 1993; 265:R1148-R1154

RELATED ARTICLE: KEY POINTS

* Dyshidrotic dermatitis of the palms is a common form of eczema of unknown etiology but thought to reflect activation of proinflammatory cytokines and cell adhesion molecules.

* The hypoxemia, autonomic arousal, and sleep loss accompanying sleep apnea may promote tissue inflammation.

* A case of sleep apnea with eczema of the palms (pompholyx), refractory to steroids, was noted to show completion resolution of dermatitis after successful use of nasal continuous positive airway pressure.