EMERGENCY CASE REPORT
Topical Ethyl Ether Therapy of Herpes Simplex Lesions Roy G. Farrell, MD Robert S. Nesland, MD Yakima, Washington
A s i m p l e a n d effective m e t h o d o f t r e a t i n g h e r p e s s i m p l e x l e s i o n s u s i n g topical application of ethyl ether relieves pain almost immediately and a b o r t s p r o g r e s s i o n o f the lesion. The t h e r a p e u t i c r a t i o n a l e for u s i n g this m o d a l i t y is b a s e d o n the ability o f e t h e r to p e n e t r a t e the e p i d e r m i s a n d to d e s t r o y the e t h e r sensitive e n v e l o p e o f the virus. A d e c r e a s e in f r e q u e n c y and even elimination of recurrences has been suggested.
Farrell RG, Nesland RS: Topical ethyl ether therapy of herpes simplex lesions. JACEP 6:372-373, August, 1977. herpesvirus hominis; skin diseases, bullous. INTRODUCTION
Recurrent, self-limiting, herpes simplex c u t a n e o u s lesions will affect from 50~ to 75~ of the adult populat i o n a t some t i m e . 1 P a t i e n t s w i t h t h e s e l e s i o n s f r e q u e n t l y p r e s e n t to the e m e r g e n c y d e p a r t m e n t because of t h e i r discomfort and cosmetic embarrassment. Some h a v e a d v o c a t e d the use of p h o t o a c t i v e d y e s to t r e a t h e r p e s progenitalis and herpes labialis. However, the recent study by Myers et al 2 h a s d e m o n s t r a t e d t h a t t h e r e is no s i g n i f i c a n t difference in n e u t r a l red and l i g h t t r e a t m e n t and placebo and light treatment. Furthermore, t h e y r e c o m m e n d t h a t this controvers i a l t r e a t m e n t be d i s c o n t i n u e d because of t h e p o t e n t i a l oncogenicity of the p h o t o d y n a m i c a l l y t r e a t e d herpes simplex virus. From the Emergency Department, St. Elizabeth Hospital, Yakima, Washington. Address for reprints: Roy G. Farrell, MD, Emergency Department, Group Health Hospital, 201 16th Avenue East, Seattle, Washington 981~12.44/372
U n t i l we b e g a n to use topical e t h e r t h e r a p y , our t r e a t m e n t of t h e s e lesions h a d been limited to s y m p t o m a tic measures. The lesions g r a d u a l l y resolved over 7 to 14 days, b u t often recurred. The first r e p o r t e d t r i a l of topical e t h e r t r e a t m e n t of h e r p e s s i m p l e x lesions, by N u g e n t and Chou, 8 was s t i m u l a t e d by t h e k n o w l e d g e t h a t the herpes simplex virus was subject to e t h e r i n a c t i v a t i o n in v i t r o . A s e c o n d r e p o r t , b y P a s r i c h a et al, 4 documents success w i t h topical e t h e r t h e r a p y in both herpes labialis and herpes progenitalis. This r e p o r t also indicates t h a t recurrences of the lesions m a y be reduced and, in some cases, e l i m i n a t e d by r e p e a t e d t r e a t m e n t w i t h ether. We h a v e b e e n t r e a t i n g h e r p e s simplex lesions w i t h topical e t h e r in our e m e r g e n c y d e p a r t m e n t for t h e p a s t y e a r w i t h u n i f o r m l y good results. These tender, vesicular lesions u s u a l l y become painless a l m o s t imm e d i a t e l y and show evidence of resol u t i o n , w i t h d r y i n g of t h e v e s i c l e s
and a m a r k e d decrease in surround. ing e r y t h e m a , w i t h i n 24 to 48 hour~ METHOD
OF TREATMENT
A s m a l l cotton pledget is soaked~ ethyl e t h e r and placed over the en t i r e lesion for five minutes. The ethe is r e a p p l i e d occasionally as it evap~ rates. E v a p o r a t i o n is reduced by c0t e r i n g t h e c o t t o n p l e d g e t with th p a l m of t h e gloved hand. The lesi0~I a n d t h e s k i n a r o u n d i t blanche~ white d u r i n g the process. A well yen. t i l a t e d room free from any electrid e q u i p m e n t or fire hazard is an essen t i a l precaution. This t r e a t m e n t is peated in 12 to 24 hours and again ii 48 hours if necessary. In our experJ ence f u r t h e r t r e a t m e n t has not beel required. Some b u r n i n g pain on in i t i a l a p p l i c a t i o n is r a p i d l y follows by r e l i e f of p a i n and itching. All th l e s i o n s w e r e d r y a n d showed evi d e n c e of h e a l i n g w i t h i n 24 to hours_ CASE Case
REPORTS .
-
" ,
w i t h a h e r p e s lesion of the lip tha had r e c u r r e d over several years. Tb~ lesion w a s t r e a t e d for five minut~ w i t h ether. Follow-up after 24 hou~ showed t h e lesion to be drying and nonpainful. She was r e - t r e a t e d oat more and told t o r e t u r n if needed. :] lesion C a s e N u m b e r T w o . The history of~t°I a 4-year-old girl with a
6:8 (Aug) 1977 , , ~ J
-ent herpes lesions of the r i g h t c~r~k ,vas t r e a t e d w i t h e t h e r for five cbee,,,s The lemon r e g r e s s e d and did Not r e q u i r e f u r t h e r follow-up. ~he lesion h a s r e c u r r e d twice a n d has been s u c c e s s f u l l y t r e a t e d e a c h Line with one application of ether. case N u m b e r T h r e e . A 25-year0]dman p r e s e n t e d w i t h a 24-hour old herpes l a b i a i i s l e s i o n a n d w a s treated with e t h e r for five m i n u t e s . I~*as m o d e r a t e l y improved b u t still painful at 24 h o u r s . He w a s retreated with e t h e r and seen 24 hours later at which t i m e t h e lesion w a s crusted over and much less red and painful. The p a t i e n t has had one recurrent l e s i o n t h a t h a s a l s o r e sponded to topical ether. Case N u m b e r F o u r . A 20-year01d woman w i t h a swollen, painful, blistered lesion of t h e left upper lip was treated 12 hours after onset w i t h topical ether, W h e n r e - e x a m i n e d 24 hours l a t e r , t h e l e s i o n w a s d r y , crusted over and h e a l i n g well. There have been no f u r t h e r recurrences.
~)
6:8 (Aug)i977
DISCUSSION A n e x c e l l e n t r e v i e w of t h e r a tionale for topical ethyl e t h e r applic a t i o n in r e c u r r e n t herpes s k i n lesions was r e c e n t l y presented by Sabin. 1 The virus is t h o u g h t to r e m a i n l a t e n t in the e p i d e r m a l cells of the affected areas between recurrent eruptions. E t h e r destroys the herpes simplex v i r u s in vitro by a c t i n g on i t s l i p i d c o n t a i n i n g m e m b r a n e . It also easily p e n e t r a t e s the e p i d e r m i s and acts as a local •anesthetic. Theor e t i c a l l y , if a p p l i e d at the first app e a r a n c e of t h e lesion or its symptoms, e t h e r would be capable of killi n g or i n a c t i v a t i n g the virus in the e p i d e r m i s t h u s a b o r t i n g further dev e l o p m e n t of t h e lesion and p e r h a p s reducing t h e frequency of r e c u r r e n t a t t a c k s or p r e v e n t i n g f u r t h e r recurrences altogether. The use of chloroform has a s i m i l a r effect on the v i r u s in vitro a n d h a s been suggested ~ as an a l t e r n a t i v e to ether. There have been no published reports of t r e a t m e n t of h e r p e s zoster
lesions by topical ether. The site of p e r s i s t e n c e of t h e l a t e n t v i r u s in h e r p e s zoster is felt to be the dorsal r o o t g a n g l i o n r a t h e r t h a n t h e epidermis; however, the p a t h o g e n e s i s of t h e e p i d e r m a l lesion i t s e l f m a y be c o m p a r a b l e . A l t h o u g h our t r i a l of e t h e r t h e r a p y in two p a t i e n t s w i t h herpes zoster h a s not been successful in a l t e r i n g the course of the disease, topical e t h e r t h e r a p y in herpes zoster lesions deserves further clinical trial.
REFERENCES
1. Sabin AB: Misery of recurrent herpes: what to do? N Engl J IVied 293"986-987, 1975. 2. Myers MG, Oxman MN, Clark JE, et al: Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections. N Engl J Med 293:945949, 1975. 3. Nugent GR, Chou SM: Treatment of labial herpes. J A M A 224:132, 1973. 4. Pasricha JS, Nayyar KC, Pasricha A: A new method for treatment of herpes simplex. Arch Dermatol 107:775, 1973.
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Topical Ethyl Ether Therapy of Herpes Simplex Lesions Roy G. Farrell, MD Robert S. Nesland, MD Yakima, Washington
A s i m p l e a n d effective m e t h o d o f t r e a t i n g h e r p e s s i m p l e x l e s i o n s u s i n g topical application of ethyl ether relieves pain almost immediately and a b o r t s p r o g r e s s i o n o f the lesion. The t h e r a p e u t i c r a t i o n a l e for u s i n g this m o d a l i t y is b a s e d o n the ability o f e t h e r to p e n e t r a t e the e p i d e r m i s a n d to d e s t r o y the e t h e r sensitive e n v e l o p e o f the virus. A d e c r e a s e in f r e q u e n c y and even elimination of recurrences has been suggested.
Farrell RG, Nesland RS: Topical ethyl ether therapy of herpes simplex lesions. JACEP 6:372-373, August, 1977. herpesvirus hominis; skin diseases, bullous. INTRODUCTION
Recurrent, self-limiting, herpes simplex c u t a n e o u s lesions will affect from 50~ to 75~ of the adult populat i o n a t some t i m e . 1 P a t i e n t s w i t h t h e s e l e s i o n s f r e q u e n t l y p r e s e n t to the e m e r g e n c y d e p a r t m e n t because of t h e i r discomfort and cosmetic embarrassment. Some h a v e a d v o c a t e d the use of p h o t o a c t i v e d y e s to t r e a t h e r p e s progenitalis and herpes labialis. However, the recent study by Myers et al 2 h a s d e m o n s t r a t e d t h a t t h e r e is no s i g n i f i c a n t difference in n e u t r a l red and l i g h t t r e a t m e n t and placebo and light treatment. Furthermore, t h e y r e c o m m e n d t h a t this controvers i a l t r e a t m e n t be d i s c o n t i n u e d because of t h e p o t e n t i a l oncogenicity of the p h o t o d y n a m i c a l l y t r e a t e d herpes simplex virus. From the Emergency Department, St. Elizabeth Hospital, Yakima, Washington. Address for reprints: Roy G. Farrell, MD, Emergency Department, Group Health Hospital, 201 16th Avenue East, Seattle, Washington 981~12.44/372
U n t i l we b e g a n to use topical e t h e r t h e r a p y , our t r e a t m e n t of t h e s e lesions h a d been limited to s y m p t o m a tic measures. The lesions g r a d u a l l y resolved over 7 to 14 days, b u t often recurred. The first r e p o r t e d t r i a l of topical e t h e r t r e a t m e n t of h e r p e s s i m p l e x lesions, by N u g e n t and Chou, 8 was s t i m u l a t e d by t h e k n o w l e d g e t h a t the herpes simplex virus was subject to e t h e r i n a c t i v a t i o n in v i t r o . A s e c o n d r e p o r t , b y P a s r i c h a et al, 4 documents success w i t h topical e t h e r t h e r a p y in both herpes labialis and herpes progenitalis. This r e p o r t also indicates t h a t recurrences of the lesions m a y be reduced and, in some cases, e l i m i n a t e d by r e p e a t e d t r e a t m e n t w i t h ether. We h a v e b e e n t r e a t i n g h e r p e s simplex lesions w i t h topical e t h e r in our e m e r g e n c y d e p a r t m e n t for t h e p a s t y e a r w i t h u n i f o r m l y good results. These tender, vesicular lesions u s u a l l y become painless a l m o s t imm e d i a t e l y and show evidence of resol u t i o n , w i t h d r y i n g of t h e v e s i c l e s
and a m a r k e d decrease in surround. ing e r y t h e m a , w i t h i n 24 to 48 hour~ METHOD
OF TREATMENT
A s m a l l cotton pledget is soaked~ ethyl e t h e r and placed over the en t i r e lesion for five minutes. The ethe is r e a p p l i e d occasionally as it evap~ rates. E v a p o r a t i o n is reduced by c0t e r i n g t h e c o t t o n p l e d g e t with th p a l m of t h e gloved hand. The lesi0~I a n d t h e s k i n a r o u n d i t blanche~ white d u r i n g the process. A well yen. t i l a t e d room free from any electrid e q u i p m e n t or fire hazard is an essen t i a l precaution. This t r e a t m e n t is peated in 12 to 24 hours and again ii 48 hours if necessary. In our experJ ence f u r t h e r t r e a t m e n t has not beel required. Some b u r n i n g pain on in i t i a l a p p l i c a t i o n is r a p i d l y follows by r e l i e f of p a i n and itching. All th l e s i o n s w e r e d r y a n d showed evi d e n c e of h e a l i n g w i t h i n 24 to hours_ CASE Case
REPORTS .
-
" ,
w i t h a h e r p e s lesion of the lip tha had r e c u r r e d over several years. Tb~ lesion w a s t r e a t e d for five minut~ w i t h ether. Follow-up after 24 hou~ showed t h e lesion to be drying and nonpainful. She was r e - t r e a t e d oat more and told t o r e t u r n if needed. :] lesion C a s e N u m b e r T w o . The history of~t°I a 4-year-old girl with a
6:8 (Aug) 1977 , , ~ J
-ent herpes lesions of the r i g h t c~r~k ,vas t r e a t e d w i t h e t h e r for five cbee,,,s The lemon r e g r e s s e d and did Not r e q u i r e f u r t h e r follow-up. ~he lesion h a s r e c u r r e d twice a n d has been s u c c e s s f u l l y t r e a t e d e a c h Line with one application of ether. case N u m b e r T h r e e . A 25-year0]dman p r e s e n t e d w i t h a 24-hour old herpes l a b i a i i s l e s i o n a n d w a s treated with e t h e r for five m i n u t e s . I~*as m o d e r a t e l y improved b u t still painful at 24 h o u r s . He w a s retreated with e t h e r and seen 24 hours later at which t i m e t h e lesion w a s crusted over and much less red and painful. The p a t i e n t has had one recurrent l e s i o n t h a t h a s a l s o r e sponded to topical ether. Case N u m b e r F o u r . A 20-year01d woman w i t h a swollen, painful, blistered lesion of t h e left upper lip was treated 12 hours after onset w i t h topical ether, W h e n r e - e x a m i n e d 24 hours l a t e r , t h e l e s i o n w a s d r y , crusted over and h e a l i n g well. There have been no f u r t h e r recurrences.
~)
6:8 (Aug)i977
DISCUSSION A n e x c e l l e n t r e v i e w of t h e r a tionale for topical ethyl e t h e r applic a t i o n in r e c u r r e n t herpes s k i n lesions was r e c e n t l y presented by Sabin. 1 The virus is t h o u g h t to r e m a i n l a t e n t in the e p i d e r m a l cells of the affected areas between recurrent eruptions. E t h e r destroys the herpes simplex v i r u s in vitro by a c t i n g on i t s l i p i d c o n t a i n i n g m e m b r a n e . It also easily p e n e t r a t e s the e p i d e r m i s and acts as a local •anesthetic. Theor e t i c a l l y , if a p p l i e d at the first app e a r a n c e of t h e lesion or its symptoms, e t h e r would be capable of killi n g or i n a c t i v a t i n g the virus in the e p i d e r m i s t h u s a b o r t i n g further dev e l o p m e n t of t h e lesion and p e r h a p s reducing t h e frequency of r e c u r r e n t a t t a c k s or p r e v e n t i n g f u r t h e r recurrences altogether. The use of chloroform has a s i m i l a r effect on the v i r u s in vitro a n d h a s been suggested ~ as an a l t e r n a t i v e to ether. There have been no published reports of t r e a t m e n t of h e r p e s zoster
lesions by topical ether. The site of p e r s i s t e n c e of t h e l a t e n t v i r u s in h e r p e s zoster is felt to be the dorsal r o o t g a n g l i o n r a t h e r t h a n t h e epidermis; however, the p a t h o g e n e s i s of t h e e p i d e r m a l lesion i t s e l f m a y be c o m p a r a b l e . A l t h o u g h our t r i a l of e t h e r t h e r a p y in two p a t i e n t s w i t h herpes zoster h a s not been successful in a l t e r i n g the course of the disease, topical e t h e r t h e r a p y in herpes zoster lesions deserves further clinical trial.
REFERENCES
1. Sabin AB: Misery of recurrent herpes: what to do? N Engl J IVied 293"986-987, 1975. 2. Myers MG, Oxman MN, Clark JE, et al: Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections. N Engl J Med 293:945949, 1975. 3. Nugent GR, Chou SM: Treatment of labial herpes. J A M A 224:132, 1973. 4. Pasricha JS, Nayyar KC, Pasricha A: A new method for treatment of herpes simplex. Arch Dermatol 107:775, 1973.
373/45
