SPECIAL CONTRIBUTION bite, brown recluse spider

The Diagnosis and Treatment of Brown Recluse Spider Bites

We reviewed our experience with 95 patients who carried the diagnosis of brown recluse spider bite between 1983 and 1986 and identified a reference group of 17 with confirmed bites. Eight men and seven women, average age 32 years, presented within 33 hours following the bites. The most common symptoms were pain, pruritus, malaise, chills, sweats, and rash. Patients were randomized into three treatment groups: dapsone, brown recluse spider antivenom, or combination therapy. All patients were treated with erythro- mycin, ff two patients with very severe lesions were excluded, patients in all groups healed their wounds in an average of 20 days. A comparison of our treatment was attempted with all other bites previously confirmed in the literature, but historical data were incomplete and no conclusions could be drawn. [Rees R, Campbell D, Rieger E, King LE: The diagnosis and treat- ment of brown recluse spider bites. Ann Emerg Med September I987;16:945- 949./

INTRODUCTION Ever since Atkins and Wingo 1 proved that Loxosceles reclusa, the brown

recluse (BR) spider (Figure) induced cutaneous necrosis, increasing clinical interest has been focused on the diagnosis and t rea tment of the BR bite. Although s t e ro ids , z 9 ant ib iot ics , ,~ ,m,u s u r g i c a l excis ion,4,1zJ 3 an t i - histamines, ~4 dapsone,~L 15 and expectant observation ~6 have been reported to be effective, an insufficient number of documented cases has been re- ported for confidence that any specific therapy was beneficial (Table 1). Unfor- tunately, these data are difficult to interpret because many t reatment reg- imens were followed and the number of patients treated by each investigator was small.

In this report the clinical features of a large group of patients (n = 95) wi th pathognomonic or documented bites were reviewed. These patients were se- lected from a large group of patients who were evaluated for possible BR bites, but lacked confirmatory historic or visual evidence. In this series, pa- tients were t reated wi th dapsoneH, ~s and/or specific BR antivenom.]r , ~a These data provide the clinical research basis for our current recommenda- tions for therapy of BR bites.

MATERIALS A N D M E T H O D S The patients for our study were selected after referral to the Vanderbilt

University Emergency Depar tment or to the authors in the plastic surgery or dermatology clinics. All patients were treated following a protocol approved by the Vanderbilt Inst i tut ional Review Board for the t rea tment of BR spider bites. Informed consent was obtained. Patients were treated in one of three groups: dapsone 100 mg PO QD; BR ant ivenom 2 mg/mL intralesionally; or dapsone 100 mg PO QD and BR ant ivenom intralesionally. All patients who refused t rea tment in the protocol received steroids and antibiotics, as that was the standard of care in Middle Tennessee during the study period.

Antivenom was raised in rabbits for this s tudy as previously described, lr Immunoreactivity of each preparation was confirmed wi th electroblot trans- fer of BR spider venom on nitrocellulose paper and stain wi th peroxidase anti-peroxidase. ~r The an t ivenom preparat ion inhib i ted sphingomyel inase activity of the BR venom invitro and in gross lesions in rabbits37 We pu- rified IgG from the hyper immune sera by protein A Sepharose CL-4B column

Riley Rees, MD*t Douglas Campbell, MD* Erik Rieger, MD*t Lloyd E King, MD, PhD*I Nashville, Tennessee Tucson, Arizona

From the Departments of Plastic Surgery and Medicine (Dermatology), Vander- bilt University;* Nashville Veterans Administration Medical Center, Nashville, Tennessee;t and the Department of Emergency Medicine, University of Arizona, Tucson, Arizona.~

Received for publication February 22, 1987. Revision received May 22, 1987. Accepted for publication June 2, 1987.

Presented at the UAEM/IRIEM Research Symposium on Environmental Emergencies in Clearwater Beach, Florida, February 1987.

Address for reprints: Riley Rees, MD, Department of Surgery, Nashville VA Medical Center. 1310 24th Avenue South, Nashville, Tennessee 37203.

16:9 September 1987 Annals of Emergency Medicine 945/45

SPIDER BITES Rees et al

TABLE 1. Historical accounting of confirmed,* treated brown recluse bites

Spider Source Species Anderson 2 ?Reclusa

Auer 3 Reclusa

Reclusa

Reclusa

Berger 14 Reclusa

Reclusa

Duffeyl 6 Reclusa

Eichned 3 Reciusa

Hershey 4 Fleclusa

Reclusa

Reclusa

King 1~ Reclusa

Mara 5 Reclusa

Reed 6 Reclusa

Reclusa

Reclusa

Russell12 Unicolor

Unicolor

Unicolor

Arizonica

Schmaus 8 Rufescens

Schreiber ~0 Arizonica

Taylor 7 Reclusa

Truman 9 Reclusa

Reclusa

Elapsed Erythema Incipient Time Area Necrosis

Site (hr) (cm) (cm) Treatment Leg 52 ? 24 Steroids/dialysis

Trunk >12 ? 0.2 Steroids (PO and IM)

Hand ? ? 0 Steroids (PO and IM)

Hand 24 0 ? Steroids and antibiotic

Trunk 10 5 0.2 Antihistamine

Arm 3 1.5 0 Antihistamine

Leg <48 9 2.0 None

Trunk 168 ? 9 Excision/steroids

Trunk >12 ? 0.2 Steroids (PO and IM)

Hand ? 9 ~ Steroids (PO and IM)

Hand ? ? ? Late excision/graft

Leg 48 32 ? Dapsone/antibiotics

Face 4 9 Present Steroids IV

Leg 1.5 8 Present Steroids (PO, IM, ID)

Eoot 24 9 7.0 Steroids (PO)

Trunk 12 2,5 None Steroids (IM)

Hand 18 9 1.0 Excision/metronidazole

Hand 8 ? 0.3 Steroids/excision

Trunk 96 3.0 Present Excision/graft

Leg 12 9 Present Excision

Arm 120 0.3 Present Local soaks

Hand 7 2.0 0.5 Antibiotics

Trunk 14 0.5 None Steroids (PO)

Trunk 6 9 ? Steroids (ID)

Trunk 6 9 9 Steroids (ID)

species sometimes was in question. *All bites were documented, but

Outcome/ Healing 1 year

?

-2

> 9 days

> 5 days

3 days

6 weeks ?

hospital 1 day

hospital 3 days

5 weeks

14 days

6 weeks

11 weeks

30 days

12 days

17 days

6 weeks

>4 weeks

3 weeks

9

3 months

14 days

7 days

7 days

chromatography and eluted the IgG fraction wi th 0.1 M glycine at pH 2.6 us ing a s tandard t echn ique of Ey.19 Antibody fractions used in these stud- ies were sterilized with a Millipore fil- ter (0.2 tzm) and fractions tes ted for e n d o g e n o u s p y r o g e n u s i n g t e m - pera ture assay in rabbi t s (Amer ican Sc ience A s s o c i a t i o n , N o r t h w o o d , Ohio). Vials were frozen and stored at - 2 0 C in the ED.

If the patient saw the spider, felt the spider, or had a c l inical ly typical le- sion, he was entered into the treat- ment protocol. The typical lesion was erythematous wi th a pustular center. In severe lesions, early central necro- sis was present. Patients seen more than 48 hours after the bite were ran-

domized into the dapsone only treat- ment group because previous data had suggested that the lesion had reached i t s m a x i m u m i n t e n s i t y by t h a t t i m e . zo W h e n p a t i e n t s w e r e r an - domized into the an t ivenom groups, 0.1 mL of ant ivenom was injected in- t radermally into the forearm 30 min- utes prior to t reatment to test for al- lergy. None were excluded. All study patients were treated with erythromy- cin 400 mg PO QID, and ice packs were applied in termi t ten t ly to the bite site unt i l the patient was pain free. zo

Between 1983 and 1986, of the 95 patients entered in the t reatment pro- tocol, 29 had a clinically typical bite, 31 felt the sting, 18 saw the spider, and 17 found the spider. There were 43

TABLE 2. Symptoms and signs following confirmed brown recluse spider bites

Symptoms* Total (%)

Pain 14/17 (82)

Pruritus 8/17 (47)

Malaise 7/17 (41)

Chills/sweats 6/17 (35)

*Other reported symptoms included gastrointestinal upset (5), myalgias, dizziness, dypsnea, and headache.

46/946 Annals of Emergency Medicine 16:9 September 1987

FIGURE. Brown recluse spider with the "fiddle" noted by an arrow.

TABLE 3. Clinical signs of brown recluse bite when first s g e n

Signs* No. of Cases (%) Erythema 16/17 (94) Cellulitis 7/17 (41) Rash 5/17 (29) Blister 5/17 (29) *Other observed signs included angioedema (4), urticaria (2) and lymphangitis (1).

male patients and 52 female patients, with an average age of 39 ÷ 6 years. In our experience, a frequent pat ient sign and symptom complex included pain (94), redness (78), i tching (69), and headache (31). Many patients had mul- tiple c o m p l a i n t s w h e n f i r s t seen .

Physical findings at the bite site and su r round ing sk in inc luded ce l lu l i t i s (65), blister (51), and rash (31). Elevated temperature (> 37.7C)(24) was noted o c c a s i o n a l l y . A l l p a t i e n t s in t h i s study were treated as outpat ients and examined weekly unti l the lesion was healed.

RESULTS The purpose of this s tudy was to

definitely test the efficacy of dapsone, antivenom, and a combinat ion of dap- sone and antivenom. We excluded 78 patients from the study group, because only 17 had a confirmed bite. These 17 patients were seen wi thin 96 hours of envenomation and brought the BR spi- der for posi t ive ident i f ica t ion by the inves t iga tors and /o r the s ta te ento- mologist. Although 110 patients were excluded, it is clear from our s tudy that there was a close correlation be- tween the excluded pat ients (78) and the reference group (17). The data from

the reference group were presented for analysis to e l iminate the possible in- clusion of patients incorrectly identi- fied as having BR spider bites.

In the reference group of pat ients , there were eight men and nine wom- en, wi th no significant difference be- tween sexes in age, height, weight, or t ime elapsed before treatment. Collec- tively, these patients were seen by one of the investigators an average of 33 hours after the bite and had received no t rea tment before arrival. The mean age was 32 years (range, 1.5 to 85 years).

Cl inical presenta t ion in the refer- ence group was similar to that in all pa t i en t s t rea ted in the study. Pain, p r u r i t i s , m a l a i s e , and c h i l l s w i t h sweats were the most common symp- toms noted at the t ime of presentat ion (Table 2). Mul t i p l e s y m p t o m s were o f t en no t ed , p a r t i c u l a r l y m a l a i s e . There were obvious signs of inflam- matory tissue injury noted in the ref- erence group, including erythema, cel- lu l i t i s , rash, and b l i s t e r f o r m a t i o n (Table 3). The rash was cha rac te r - ist ically a fine, macular eruption over the ent ire body, whi le cel lul i t is was generalized l ike an infect ion on the extremity. Brown recluse spider bites were mos t of ten found on the a rm (36%), leg (21%), t r u n k (21%), and hand (22%). Men were b i t t en more often on the leg, while women were bit ten more often on the arm. In the reference group, there were no bites on the hand, perineum, or buttocks. The average lesion size at the t ime of pre- sentation was 5.3 cm.

A summary of the t rea tment groups and their outcomes is l isted (Table 4). Six patients received dapsone, five re- ceived antivenom, and five were treat- ed with the ant ivenom and dapsone. Two of the six pat ients were treated with the dapsone alone (Group 1) be- cause they were allergic to the anti- v e n o m fo l l owing sk in t es t ing . Re- gardless of treatment, all lesions were healed wi th in 20 _+ l l days, except for two patients . Both of these (cases 1 and 15) had significantly larger areas of skin necrosis at the t ime of presenta- t ion than did the o the r pa t ien t s . If these two patients are excluded from the outcome and wound healing col- umn, then all groups appear to have equal efficacy, although the size of the

16:9 September 1987 Annals of Emergency Medicine 947/47

SPIDER BITES Rees et al

TABLE 4. Outcome from time of presentation to conclusion of therapy in the reference group

Diameter of Diameter of Treatment Incipient Erythema

Group* Caset Site Necrosis (cm) (cm) 1 1 Arm 3.0 6.5 1 2 Trunk 1.0 0.7

1 3 Leg 1.0 1,5

1 4 Arm 1.0 9.0

1 5 Foot 0.0 0,5

1 6 Leg 1.0 32.0

x = 0 . 8 + 0 . 4 x = 8 . 7 + 1 3 . 5

2 7 Face 0.0 0.0 2 8 Trunk 0.0 0.0

2 9 Leg 0.5 5.0

2 10 Arm 0.5 0.5

2 11 Arm 0.0 1.0

x = 0 . 2 ÷ 0 . 3 x=1.3_+2.1 3 12 Trunk 1.0 2.5

3 13 Leg 0.0 10.0

3 14 Face 0.0 0.2

3 15 Arm 4.0 14.0

3 16 Face 0.0 2,5

x=0.2_+0.5 x=3.8_+4.3 *Group 1 dapsone; Group 2, antivenom; Group 3, dapsone and antivenom. tCases 1 and 15 excluded from calculations (see text). *Previously reported J o §No statistically significant difference in the treatment groups (P < .5).

Outcome and Healing Time§

(days) 3-cm scar (60)1-

No scar (30)

2-cm scar (14)

< l - c m scar (7)

No scar (14)

No scar (14)*

x=16_+8

no scar (7)

no scar (30)

2-cm scar (30)

< l - c m scar (30)

no scar (4)

x=20_+13

No scar (14)

No scar (30)

No scar (19)

6-cm scar (120)t

No scar (35)

x = 2 0 + 1 1

clinical groups is small.

DISCUSSION Cutaneous loxoscelism is a wide-

spread clinical problem2A, h21 in the southeastern United States and is in- creasing in frequency throughout the North American continent. Because the clinical diagnosis is difficult due to the initial appearance of the lesion, treatment is often delayed until frank necrosis has occurred. Currently, there is no diagnostic test available to aid the physician in making a diagnostic or therapeutic decision. In this study, we attempted to define a reference pa- tient data base with the confirmed BR bite. Clearly, in the absence of a refer- ence control group, our data must be considered preliminary. Comparisons wi th h i s to r ica l t r e a t m e n t of con- firmed bites provide Iittle useful infor- mation, because the duration of heal- ing is long {> 40 days) and the range is great (one to 360 days). In our group of patients, pain, itching, and redness

were the hallmarks of the clinical syn- drome, as one or all were present in every patient. A careful clinical his- tory proved to be a very useful tech- nique in establishing the diagnosis of cutaneous loxoscelism,

Our novel approach to the treat- ment of the bites with the leukocyte inhibitor dapsone and a specific anti- venom was based on previous clinical and laboratory data. J l, ~5,1~ Our experi- ence with dapsone demonstrated that it eliminated the need for surgery in m a n y BR bites. It is not surprising that in the reference group, dapsone- treated wounds healed in an average of 17 days. Once necrosis had occurred, treatment was less effective. Our use of the experimental ant ivenom sug- gested it was mos t effective in pa- tients who had not yet developed the clinical lesion. This is most consistent with the action of the antibody, which is d i rec ted at i nh ib i t i ng the bio- chemical activity of sphingomyelinase enzyme in the BR venom. Once the

inflammatory reaction had developed, a n t i v e n o m appeared less effect ive {cases 9 and 10). The combination of dapsone and ant ivenom would seem to be the most effective therapy, be- cause t h e y act t h r o u g h d i f f e ren t mechanisms. However, in this small clinical sample, all t reatment groups appeared to be equally effective. Com- parisons of our data to the other docu- mented cases appear futile because the i n f o r m a t i o n is i n c o m p l e t e in many previous clinical studies.

It is clear from our data that if skin necrosis is prevented, objectionable scarring and delayed wound healing are avoided. Our experience wi th a small series of patients who developed

pyoderma gangrenosum following the BR bite 22 suggests that skin necrosis is the "turnkey" mechanism for this event. A patient with a hand bite is particularly prone to develop loss of hand function or a painful extremity after a BR bite with skin loss.Z~ If the BR bite is promptly recognized and

48/948 Annals of Emergency Medicine 16:9 September 1987

t h e r apy i n s t i t u t e d , t h e o u t c o m e i s usually favorable . O p t i m a l t h e r a p y in our i n s t i t u t i o n i n c l u d e s i n t e r m i t t e n t ice packs, 24 e l eva t i on , a n d a n t i b i o t i c s {erythromycin) , a l o n g w i t h d a p s o n e , and/or a n t i v e n o m . We h a v e r e s e r v e d steroid t h e r a p y for p a t i e n t s w i t h sys- t e m i c s y m p t o m s w h e n l a b o r a t o r y data suppor t i t s use . 25

C O N C L U S I O N In th is s tudy, w e r e p o r t e d o u r expe-

r i ence u s i n g a n o v e l a p p r o a c h t o brown r e c lu se s p i d e r b i t e s u s i n g c o m - b ina t ion t h e r a p y to m a x i m i z e e f fec- t iveness a g a i n s t t h i s s e v e r e c u t a n e o u s injury. C lea r ly , m o r e p a t i e n t s w i t h conf i rmed b i t e s a n d s t r i n g e n t c o n t r o l s will be n e e d e d to v a l i d a t e o u r c o n c l u - sions.

The authors gra te fu l ly acknowledge the technical ass is tance of Caryl Gates, and thank Tom Ebers for manusc r ip t prepara- tion. This work was suppor ted by the Vet- erans Adminis t ra t ion .

REFERENCES 1. Atkins JA, Wingo CW, Sodeman WA: Proba- ble cause of necrotic spider bite in the Midwest. Science 1957;126:73.

2. Anderson PC: Brown recluse spider bites: What's new on loxoscelism - - 1978? Mo Med 1977; 74:549-556.

3. Auer AI, Hershey FB: Surgery for necrotic bites of the brown spider. Arch Surg 1974;108: 612-618.

4. Hershey FB, Aulenbacher CE: Surgical treat- ment of brown spider bites. Ann Surg 1969;170: 300-308.

5. Mara JE, Myers BS: Brown spider bites: Treat- ment with hydrocortisone. Rocky Mt Med J 1977;74:257-258.

6. Reed HB Jr, Hackman RH, Fesmire FM: Vari- ation in severity of loxoscelism. J Tenn Med As- soc 1968;61:1097-1102.

7. Taylor MAH, Olive AT: Brown recluse spider bites. NC Med ] 1972;33:421-424.

8. Schmaus LF: Case of arachnoidism (spider bite), lAMA 1929;92:1265-1266.

9. Truman GC: Brown spiders (letter). Ariz Med 1974;31:948.

10. Schreiber MM, Shapiro SI: Necrotic arach- noidism in the southwestern United States. Cutis 1971;7:674-677.

11. King LE, Rees R: Dapsone treatment of a brown recluse spider bite. lAMA 1983;250:648.

12. Russell F, Waldron W, Madon M: Bites by the brown spiders Loxosceles unicolor and Lox- osceles arizonica in California and Arizona. Toxicon 1969;7:109-117.

13. Eichner ER: Spider bite hemolytic anemia: Positive Coombs' test, erythrophagocytosis, and leukoerythroblastic smear. Am I Clin Pathol 1984;81:683-687.

14. Berger RS: The unremarkable brown recluse spider bite. lAMA 1973;225:t109-1111.

15. Rees RS, Altenbern DE Lynch JB, et al: Brown recluse spider bites: A comparison of ear- ly surgical excision and dapsone and delayed surgical excision. Ann Surg 1985;20:2126-2130.

16. Duffey PH, Linbacher HP: Brown spider bites in Arizona. Ariz Med 1971;28:89-95.

17. Rees RS, Nanney LB, Yates RA, et al: Inter- action of brown recluse spider venom on cell membranes: The inciting mechanism? l Invest Dermatol 1984;83:270-275.

18. Rees RS, Shack RB, Withers EH, et al: Man- agement of the brown recluse spider bite. Plast Reconstr Surg 1981;68:768-773.

19. Ey PL, Prowse SJ, Jenkin CR: Isolation of pure IgG, lgG-2a and IgG-2b immunoglobulins from mouse serum using protein A-Sepharose. Immunochemistry 1978;15:429-436.

20. Rees RS, King LE: Therapy for brown re- cluse spider bites is dependent on venom per- sistence. Clin Res 1985;33:302A.

21. Dillaha CJ, Jansen GT, Honeycutt WM, et al: The gangrenous bite of the brown spider in Arkansas. l Arkansas Med Soc 1963;60:91-94.

22. Rees RS, Fields JP, King LE Jr: Brown recluse spider bite: A cause of pyoderma gangrenosum? South Med I 1985;78:283-287.

23. DeLozier JB, Reaves L, King LE, et al: Brown recluse spider bites of the upper extremity. South Med I (in press).

24. King LE, Rees RS: Brown recluse spider bites: Stay cool. lAMA 1986;254:2895-2896.

25. Rees RS, O'Leary JP, King LE Jr: The patho- genesis of systemic loxoscel ism following brown recluse spider bites. J Surg Res 1983; 3:51-60.

16:9 September 1987 Annals of Emergency Medicine 949/49