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Brown recluse spider bites to the head: three cases and a review.



Abstract

Consequences of envenomation envenomation /en·ven·om·a·tion/ (en-ven?o-ma´shun) poisoning by venom.

en·ven·om·a·tion
n.
The injection of a poisonous material by sting, spine, bite, or other similar means.
 from the bite of a brown recluse spider brown recluse spider or violin spider, poisonous nocturnal spider, Loxoceles reclusa, most common in the SE and S central United States. Adults are 3-8 in.  (Loxosceles reclusa) range from mild itching to death. The bite of this spider causes the most severe form of arthropod-induced tissue necrosis. These bites pose several challenges to the clinician in that diagnosis can be difficult, systemic manifestations can occur, and healing can be resistant to conventional measures. Bites to the head and neck--particularly the face--are uncommon, and they have not been widely reported in the otolaryngology literature. As experts in facial soft tissue, otolaryngologists and facial plastic surgeons should be able to recognize and treat these lesions. Because no laboratory test is available to identify the cause of symptoms in these cases, the diagnosis is made clinically. Early intervention can make a significant difference in cosmetic outcome, so a high index of suspicion index of suspicion Medtalk A phrase broadly used to indicate how seriously a particular disease is being entertained as a diagnosis; as an example, there is a high IOS that rapid and unexplained weight loss in an elderly Pt is due to pancreas CA, and a low IOS that  is warranted. Local wound care includes rest, ice, compression, and elevation of the affected part of the body. Drug therapy with dapsone dapsone /dap·sone/ (dap´son) an antibacterial bacteriostatic for a broad spectrum of gram-positive and gram-negative organisms; used as a leprostatic, as a dermatitis herpetiformis suppressant, and in the prophylaxis of falciparum  may limit the severity of the bite and prevent complications. Because some bites cause systemic loxoscelism, clinicians should be familiar with its manifestations. When necrosis occurs despite adequate medical treatment, reconstructive procedures should be delayed until healing is complete. We report 3 cases of brown recluse spider bites to the head. These cases illustrate the broad spectrum of the disease course, and they highlight the therapeutic challenges that these lesions pose.

Introduction

Consequences of envenomation from the bite of a brown recluse spider (Loxosceles reclusa) range from mild itching to death. Because no laboratory test is available to identify the spider's venom, the diagnosis is made clinically, based on a combination of signs, symptoms, and history. Most bites are benign, but approximately 10% become significant. (1) Scar formation appears to be more severe in areas that overlie fatty tissue, such as the eyelid. Distinguishing between patients who will develop a severe reaction and those who will not may be difficult, but appropriate intervention within the first few days can make a critical difference in outcome.

The appropriate form of local wound care of brown recluse spider bites has evolved in recent years, and it now includes the application of cool compresses rather than heat. The practice of removing toxin by curettage curettage /cu·ret·tage/ (ku?re-tahzh´) [Fr.] the cleansing of a diseased surface, as with a curet.

medical curettage
 of the subcutaneous tissue has been discredited, particularly in cosmetically important areas such as the face. Systemic treatment is controversial. The leukocyte inhibitor dapsone probably limits the severity of the bite and prevents complications. Nevertheless, the side effects of dapsone can be severe, and care is warranted in its administration. Prolonged courses of dapsone are indicated under certain conditions. When dapsone therapy is anticipated, the patient's glucose-6-phosphate dehydrogenase (G6PD G6PD glucose-6-phosphate dehydrogenase.

G6PD

glucose-6-phosphate dehydrogenase.
) level should be measured because patients who have a deficiency of this enzyme are more prone to develop hemolysis hemolysis (hĭmŏl`ĭsĭs), destruction of red blood cells in the bloodstream. Although new red blood cells, or erythrocytes, are continuously created and old ones destroyed, an excessive rate of destruction sometimes occurs.  while taking dapsone. The ideal course of therapy is to intervene early enough to avoid tissue necrosis.

Despite adequate medical treatment, healing is problematic in some patients--that is, it is slow, often requiring several months. Hyperbaric oxygen therapy Hyperbaric oxygen therapy (HBO)
A treatment in which the patient is placed in a chamber and breathes oxygen at higher-than-atmospheric pressure. This high-pressure oxygen stops bacteria from growing and, at high enough pressure, kills them.
 may play a role in treating long-standing lesions.

Reconstructive procedures are occasionally necessary. However, it is possible for pyoderma gangrenosum to develop in these wounds, and this can thwart attempts at reconstruction and even lead to a recurrence of lesions months alter the bite.

A significant number of bites are accompanied by a generalized reaction known as systemic loxoscelism. Systemic symptoms are not necessarily directly proportional to the severity of the skin lesion. The otolaryngologist should be aware of the systemic symptoms that might indicate systemic loxoscelism.

In this article, we report the cases of 3 women who experienced a brown recluse spider bite-one on the upper lip, one on the earlobe ear·lobe or ear lobe
n.
The soft, fleshy, pendulous lower part of the external ear.
, and one on the eyelid. Each case illustrates a different presentation and clinical course. The first patient presented acutely and was treated with early, aggressive therapy, which precluded the need for surgical intervention. The second patient presented after several months and experienced the difficulty of a problematic, slowly healing wound. The third patient also presented in a delayed fashion, and she exhibited symptoms of loxoscelism and significant scarring.

Case reports

Patient 1. A 55 -year-old woman was bitten on her upper lip by a brown recluse spider while she was sleeping. Within hours, she developed swelling, redness, burning, itching, and heat in the area. An outside physician prescribed 25 mg/day of dapsone along with a course of cephalexin cephalexin /ceph·a·lex·in/ (-lek´sin) a semisynthetic first-generation cephalosporin, effective against a wide range of gram-positive and a limited range of gram-negative bacteria; used as the base or the hydrochloride salt. , and the patient began to improve.

Five days later, however, she was referred to our facility because the swelling, redness, and heat had recurred. She had no fever, hematuria hematuria

Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders.
, arthralgia, myalgia, or malaise. Physical examination revealed that the area of swelling, erythema, and heat, in addition to tenderness, extended across her upper lip and down her left cheek (figure 1, A). Her blood count and G6PD level were normal, so we increased the dapsone dosage to 50 mg twice daily. We also started her on a tapering dose of oral methylprednisolone sodium succinate methylprednisolone sodium succinate

A-Methapred, Solu-Medrol, Solu-Medrone (UK)

Pharmacologic class: Glucocorticoid

Therapeutic class: Antiasthmatic, anti-inflammatory (steroidal), immunosuppressant

, and we continued her antibiotic. Finally, we prescribed a twice-daily application of topical nitroglycerin nitroglycerin (nī'trōglĭs`ərĭn), C3H5N3O9, colorless, oily, highly explosive liquid. It is the nitric acid triester of glycerol and is more correctly called glycerol trinitrate. , but we discontinued it after 2 days because it caused a headache.

[FIGURE 1 OMITTED]

Improvement was evident 2 days after her referral, although some tingling and numbness persisted. She continued to improve, and the dapsone and other drugs were stopped after 7 days (figure 1, B).

Patient 2. A brown recluse spider bit a 54-year-old woman on her left earlobe while she was sleeping on a piece of furniture that had been in storage until recently. She was treated at an outside facility with a cephalosporin, an antibiotic ointment, an anesthetic ointment, and an oral and a topical steroid.

Despite the intervention, the patient gradually began to lose part of her earlobe. Four months after the bite, she was referred to us for possible earlobe reconstruction. Her open wound site was characterized by persistent redness, severe pain, itching, and drainage (figure 2, A). She had also developed an extensive rash on her face, neck, and left arm, which was diagnosed as a contact dermatitis. Because she reported no other overt symptoms of systemic loxoscelism and because the bite had occurred 4 months earlier, we did not considerusing dapsone. Cultures yielded no growth. A biopsy indicated chronic inflammation of the skin and cartilage.

[FIGURE 2 OMITTED]

We started the patient on an oral cephalosporin and a topical antibiotic ointment, but she continued to complain of itching and pain. She was switched to an antihistamine antihistamine (ăn'tĭhĭs`təmēn), any one of a group of compounds having various chemical structures and characterized by the ability to antagonize the effects of histamine.  and a topical steroid cream. Despite these measures, her ear cartilage continued to slowly deteriorate. Four weeks later, we started her on a 3-week course of hyperbaric oxygen therapy. After 2 weeks of oxygen, the wound stabilized. Over the following year, healing was slow and incomplete, and we prescribed another 3-week course of hyperbaric oxygen. By the end of this treatment, the patient's ear had completely healed. One year later, she remained completely healed, but she declined to undergo any reconstruction of her ear (figure 2, B).

Patient 3, A 39-year-old woman was bitten by what we assumed was a brown recluse spider on the left upper eyelid while she was exploring a cave. Coincidentally, she had undergone an uneventful bilateral upper blepharoplasty Blepharoplasty Definition

Blepharoplasty is a cosmetic surgical procedure that removes fat deposits, excess tissue, or muscle from the eyelids to improve the appearance of the eyes.
 3 months earlier. Within hours of the bite, blisters developed on the lid. The patient was evaluated in an emergency room, where the lid was incised and drained. She was given intravenous and oral antibiotics and followed up by an ophthalmologist, who noted persistent swelling. She was placed on a cephalosporin and a steroid.

Three weeks after the bite, the patient was referred to us for evaluation. She complained of pain and itching at the site of the bite, along with fatigue, malaise, arthralgia, nausea, and vomiting. The wound evidenced redness, drainage, and swelling, and there was a small central area of necrosis (figure 3, A). There was no hepatosplenomegaly, but a morbilliform rash developed over her extremities. She was admitted to the hospital for a further work-up. She underwent a G6PD measurement; pending the findings of this test, she was started on low-dose dapsone (25 mg/day). Although her G6PD level was reported as normal, she developed pancytopenia pancytopenia /pan·cy·to·pe·nia/ (-sit-ah-pe´ne-ah) abnormal depression of all the cellular elements of the blood.

pan·cy·to·pe·ni·a
n.
 after 1 day of dapsone treatment. The reason for the pancytopenia was not clear, but the dapsone and the cephalosporin were discontinued. She exhibited no hemolysis or hematuria. A biopsy demonstrated chronic inflammation compatible with an arthropod bite.

[FIGURE 3 OMITTED]

The patient was discharged from the hospital, and treatment thereafter was supportive. She continued to complain of symptoms of loxoscelism (pain and itching at the site of the bite, and the fatigue, malaise, arthralgia, nausea, and vomiting), which waxed and waned during the next 3 months. She was started on hyperbaric oxygen therapy, and she began to slowly but progressively improve. After 20 sessions of oxygen therapy (6 months after the bite), the lesion healed, although there were residual scarring and tethering of the lid (figure 3, B). At that point, she was ready to undergo formal reconstruction of the eyelid.

Discussion

The brown recluse spider is also known as the necrotizing necrotizing /nec·ro·tiz·ing/ (nek´ro-tiz?ing) causing necrosis.
Necrotizing
Causing the death of a specific area of tissue. Human bites frequently cause necrotizing infections.
 spider, fiddleback spider, and violin spider (on its dorsal cephalothorax ceph·a·lo·tho·rax  
n.
The anterior section of arachnids and many crustaceans, consisting of the fused head and thorax.



cephalothorax  
 is a violin-shaped mark). Its color varies from tan to dark brown (figure 4). The adult body is 8 to 9 mm long, and the length of its leg span ranges from 25 to 50 mm.

Brown recluse spiders are found predominantly in the Southern and Midwestern United States. (2) (Because they can travel in luggage, their bites may be seen in other parts of the world, as well.) These spiders are not aggressive, and they tend to avoid humans (noise scares them off), but they will bite when they are threatened or injured. They live in warm, dry places, either outdoors (under the bark of dead trees, under rocks, and in piles of lumber and firewood) or indoors (in dark isolated places such as attics). In fact, bites are more frequent during holidays when people take decorations out of storage. Many other victims are bitten while dressing in clothing that has been undisturbed for some time or when they roll over onto a spider that has crawled into a bed. (2,3)

Controlling infestations is difficult because these spiders can survive for 6 months without food or water and because chemicals strong enough to kill them are also hazardous to humans. (4)

Skin and soft-tissue reactions. The bite of the brown recluse spider causes the most severe form of arthropod-induced tissue necrosis. Its venom is made up of nine different proteins. (5) The primary factor responsible for tissue necrosis is sphingomyelinase. (6) This enzyme interacts with the membranes of erythrocytes, platelets, and endothelial cells. (7) Although sphingomyelinase D is toxic to many types of cell, significant tissue damage requires the participation of the host's own cells, particularly neutrophils and platelets. (8) Following envenomation, the initial injury is endothelial damage to the arterioles Arterioles
Small blood vessels that carry arterial (oxygenated) blood.

Mentioned in: Retinal Artery Occlusion

arterioles,
n
 and venules venules (vēnˑ·yōōlz),
n.pl small blood vessels that merge with the veins and return blood from other tissues to the heart.
, and these vessels become occluded with thrombi thrombi /throm·bi/ (throm´bi) plural of thrombus.  made up of neutrophils and platelets. The neutrophils then degranulate and secrete prostaglandin metabolites that contribute to more endothelial damage, which leads to thrombosis, ischemia, and necrosis.

Lysis of red blood cells Red blood cells
Cells that carry hemoglobin (the molecule that transports oxygen) and help remove wastes from tissues throughout the body.

Mentioned in: Bone Marrow Transplantation

red blood cells 
 also occurs to some extent, and it can result in anemia. A spreading circumferential zone of hemorrhage, stasis, and thrombi then moves throughout the fascial layer.

Brown recluse spider bites on the face are uncommon. In one series, only 3% of bites involved the face (only 5% involved the neck). (2) These bites generally go unnoticed at first, although some patients feel a transient stinging sensation. (9) In the 10% of patients who experience a serious reaction, symptoms usually begin in 6 to 12 hours. (1) If tissue changes do not occur by 48 to 96 hours, patients usually will not develop any significant necrosis.

The diagnosis of a brown recluse spider bite is made clinically on the basis of a constellation of signs, symptoms, and history suggestive of exposure to the spider. Diagnostic laboratory tests have been developed, but none is yet commercially available. (10)

There is no relationship between the initial size of the lesion and long-term effects, so all bites must be followed by qualified medical personnel. (11) Within hours, local findings may include itching, pain, swelling, redness, blisters, or pustule pustule /pus·tule/ (pus´tul) a small, elevated, circumscribed, pus-containing lesion of the skin.pus´tular

pus·tule
n.
1.
 formation. (1) Pain is the most common symptom, and it is related either to ischemia secondary to vasospasm vasospasm /vaso·spasm/ (va´zo-) (vas´o-spazm) angiospasm; spasm of blood vessels, causing vasoconstriction.vasospas´tic

va·so·spasm
n.
 or to disruption by the toxin of myelin sheaths on nerve fibers. (12,13) Occasionally, pain becomes so severe that a sympathetic block is necessary. (14)

In cases of necrosis, patients typically develop a blister that becomes a dark-bluish macule macule /mac·ule/ (ma´kul) a discolored spot on the skin that is not raised above the surface.

mac·ule
n.
Variant of macula.
; the macule then sinks below the level of the surrounding skin. (1,15) The blister may be surrounded by an ischemic Ischemic
An inadequate supply of blood to a part of the body, caused by partial or total blockage of an artery.

Mentioned in: Antiangiogenic Therapy, Subarachnoid Hemorrhage, Ventricular Fibrillation


ischemic
 ring that is in turn encircled by an erythematous ring (the "red, white, and blue sign"). (1) Five to 7 days later, the affected area becomes necrotic and eschar eschar /es·char/ (es´kahr)
1. a slough produced by a thermal burn, by a corrosive application, or by gangrene.

2. tache noire.


es·char
n.
 forms. The necrosis rarely involves deep fascial structures such as muscles, tendons, or ligaments. (3) The eschar later separates from the surrounding healthy tissue and sloughs, leaving an ulcer. Healing is slow, requiring 2 to 4 months. (15)

Scar formation appears to be more severe in areas overlying overlying

suffocation of piglets by the sow. The piglets may be weak from illness or malnutrition, the sow may be clumsy or ill, the pen may be inadequate in size or poorly designed so that piglets cannot escape.
 fatty tissue, such as the thighs, abdomen, and buttocks buttocks /but·tocks/ (but´oks) the two fleshy prominences formed by the gluteal muscles on the lower part of the back. . (12) The eyelid, a thin layer of skin overlying a fat compartment, can be considered to be in the same category. (16) After her blepharoplasty, our patient 3 may have experienced a disruption of the fascial planes on a microscopic level, and this might have allowed for freer ingress of toxin into the fat.

Some patients have experienced persistent hypoesthesia hypoesthesia /hy·po·es·the·sia/ (-es-the´zhah) abnormally decreased sensitivity, particularly to touch.hypoesthet´ic

hy·po·es·the·sia or hy·pes·the·sia
n.
 or paresthesia paresthesia /par·es·the·sia/ (par?es-the´zhah) morbid or perverted sensation; an abnormal sensation, as burning, prickling, formication, etc.

par·es·the·sia or par·aes·the·sia
n.
, presumably pre·sum·a·ble  
adj.
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster.
 as a result of the effect of sphingomyelinase D on myelin. (13)

The necrotic lesions of the brown recluse spider bite can mimic other diseases, including erythema chronicum migrans erythema chron·i·cum mi·grans
n.
A raised erythematous ring on the skin having hard borders and a central clearing, and radiating from the site of an insect bite; it is the characteristic lesion of Lyme disease.
, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis Toxic Epidermal Necrolysis Definition

Toxic epidermal necrolysis is a rare condition that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of skin below. A reaction to a medication is the primary cause.
), erythema nodosum, erythema multiforme, herpes simplex infection, purpura fulminans, diabetic ulcer, bedsore bedsore /bed·sore/ (bed´sor) decubitus ulcer.

bed·sore
n.
A pressure-induced ulceration of the skin occurring in persons confined to bed for long periods of time.
, poison oak and poison ivy reactions, gonococcal Gonococcal
The bacteria Neisseria gonorrheae that causes gonorrhea, a sexually transmitted infection of the genitals and urinary tract. The gonococcal organism may occasionally affect the eye, causing blindness if not treated.

Mentioned in: Conjunctivitis
 arthritic dermatitis, urticaria, pyoderma pyoderma /pyo·der·ma/ (pi?o-der´mah) any purulent skin disease.

pyoderma gangreno´sum  a rapidly evolving cutaneous ulcer or ulcers, with marked undermining of the border.
, and cellulitis. (2) If the skin becomes necrotic after 24 to 72 hours, many of these clinical possibilities can be ruled out. If the diagnosis is in doubt, an internal medicine or dermatology consult is indicated.

Management of skin and soft-tissue reactions. Obviously, the ideal scenario is that the practitioner intervene early enough to avoid any loss of skin and soft tissue. Systemic treatment is controversial.

Conservative management. The basic principles of local wound care for brown recluse spiderbites include rest, ice, compression, and elevation (RICE). Applying ice or cold packs to bite sites has been shown to significantly reduce inflammation and slow the evolution of the lesion. (17) On the other hand, applying heat to the site can worsen the situation by inducing the development of blisters, necrosis, or ulcerations Ulcerations
Breaks in skin or mucous membranes that are often accompanied by loss of tissue on the surface.

Mentioned in: Hypersplenism
. (17) Heat is believed to promote necrosis by potentiating the effects of sphingomyelinase D and lipase lipase (lī`pās), any enzyme capable of degrading lipid molecules. The bulk of dietary lipids are a class called triacylglycerols and are attacked by lipases to yield simple fatty acids and glycerol, molecules which can permeate the membranes . (7)

Prophylactic agents. Prophylactic antibiotics are usually given to prevent secondary infection, although no clinical trials have addressed this specific issue. Antihistamines Antihistamines Definition

Antihistamines are drugs that block the action of histamine (a compound released in allergic inflammatory reactions) at the H1
 are administered mainly to relieve pruritus pruritus /pru·ri·tus/ (proo-ri´tus) itching.prurit´ic

pruritus a´ni  intense chronic itching in the anal region.

pruritus hiema´lis  xerotic eczema.
 and swelling. Although corticosteroids have been used for their protective effects, they have not been shown to limit the amount of skin necrosis. (18) Aspirin or heparin may be given to counteract platelet aggregation and thrombosis, but their effect is also unproven.

Dapsone. Dapsone (4,4' diaminodiphenylsulfone) inhibits neutrophil migration and endothelial attachment, and it blocks neutrophil secretion of lysosomal lysosomal

pertaining to or emanating from lysosomes.


lysosomal enzymes
enzymes located in the lysosomes.

lysosomal phospholipidosis
 enzymes. (19) Dapsone limits the severity of the bite reaction, promotes healing, and prevents complications. (20) There are case reports of patients who were treated with 50 to 200 mg/day of dapsone who experienced a marked decrease in pain, erythema, and induration induration /in·du·ra·tion/ (in?du-ra´shun)
1. sclerosis or hardening.

2. hardness.

3. an abnormally hard spot or place.
. (21-23) To date, however, no double-blind, randomized trial has been conducted to compare dapsone and placebo in humans. When dapsone is used, therapy should be continued until the epidermis becomes contiguous and there is no further exudation exudation /ex·u·da·tion/ (eks?u-da´shun)
1. the escape of fluid, cells, and cellular debris from blood vessels and their deposition in or on the tissues, usually as the result of inflammation.

2. an exudate.
. Sphingomyelinase D remains in the bite area for more than 3 weeks, so it might be necessary to continue dapsone for at least that long. (3)

Dapsone has many potential side effects, some of them dangerous. They include nausea, dizziness, fatigue, shortness of breath Shortness of Breath Definition

Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity.
, skin rash, nervousness, toxic hepatitis, cholestatic jaundice, nephrotoxicity neph·ro·tox·ic·i·ty
n.
The quality or state of being toxic to kidney cells.


nephrotoxicity(ne·fr
, and psychosis, particularly with prolonged therapy. (24-26) Hemolysis and agranulocytosis agranulocytosis (əgrăn'yəlōsītō`sis), disease in which the production of granulated white blood cells by the bone marrow is impaired.  can occur during the first few days of treatment; as mentioned, hemolysis can also occur in patients with low levels of G6PD. Our patient 3 was forced to discontinue dapsone after 1 day because her hematocrit level fell, even though her G6PD level was normal. Patients on dapsone should undergo serial blood counts to monitor for hemolysis and leukocytopenia.

Hyperbaric oxygen. In an animal study, hyperbaric oxygen therapy was found to be ineffective in reducing lesion size unless the subjects were pretreated. (27) Nevertheless, hyperbaric oxygen was beneficial in 2 of our 3 patients, presumably because it promotes angiogenesis and the formation of granulation tissue in long-standing lesions.

Curettage. In one early series of patients with brown recluse spider bites, Hollabaugh and Fernandes advocated curetting the subcutaneous tissue in the necrotic area of the lesion to prevent the local destructive actions of the toxin. (28) However, curettage is no longer recommended. Rees et al compared early curettage with dapsone therapy and found that the dapsone-treated patients had a lower incidence of delayed wound healing, less need for subsequent surgical excision, a lower rate of hospitalization, and less objectionable scarring than did patients in the curettage group. (20) Another reason that early excision is not warranted is that it is usually difficult to determine exactly how big a lesion is. Therefore, it is now recommended that surgical excision for spider bites be reserved for those patients whose eschars are stable; stability typically occurs in 6 to 10 weeks. It is especially important to eschew curettage on the face, where scarring should be avoided or minimized.

Nitroglycerin. The use of topical nitroglycerin might be supported by the results of studies that have explored the benefits of nitric oxide in tissues, (2) but to date no trial has been conducted on humans with spider bites.

Healing of skin lesions. Healing is problematic in some patients. Until recently, we did not fully understand that venom factors can remain in bite lesions for a relatively long time or that a bite we are treating is actually a recurrence rather than the initial lesion. (29) In patients with more severe bites, eschar may take months to develop and the skin may take several months more to heal. (1) These wounds may progress to significant tissue loss and spreading of ulcerations.

Delayed wound healing can occur despite appropriate medical treatment. (29) Why bites do not promptly heal is not clear, but the persistence of venom in the wound or the generation of secondary inflammatory mediators may play a role. In one study of brown recluse spider bites, Rees et al reported that some patients who had received skin grafts experienced repeated graft rejections for no obvious reason. (29) Eventually, the authors realized that these patients had developed pyoderma gangrenosum. Our patient 2 developed contact dermatitis, which manifested as several satellite lesions on the face, neck, and arm. Although the diagnosis of pyoderma gangrenosum was not made in this patient, the persistent presence of venom or secondary inflammatory mediators may have provoked the dermatitis that she did develop. Pyoderma gangrenosum as a complication of brown recluse spider bites appears to be associated with predisposing factors such as surgery near the time of the bite or a personal or family history of rheumatoid arthritis, ulcerative colitis, or Crohn's disease. (1)

Recurrent lesions may arise months after the bite and in adjacent areas. (29) Hoover et al advocated life-long follow-up at 6-month intervals in such patients to look for the development of squamous cell carcinoma squamous cell carcinoma
n.
A carcinoma that arises from squamous epithelium and is the most common form of skin cancer. Also called cancroid, epidermoid carcinoma.
. (30) Because the clinical course of healing is so difficult to predict with any brown recluse spider bite, reconstruction should not be attempted until healing is complete.

Systemic reactions. Systemic loxoscelism is less common than skin necrosis. In one series of bites, the incidence of skin necrosis was 37% and the incidence of systemic illness was 14%. (9)

Systemic symptoms include fever, chills, malaise, nausea, vomiting, arthralgias, myalgias, headache, anorexia, abdominal pain, weakness, and convulsions Convulsions
Also termed seizures; a sudden violent contraction of a group of muscles.

Mentioned in: Heat Disorders
. (1,12,15,31) Physical findings often include a morbilliform rash. (15) In more severe cases, shock may be present. As the toxin destroys blood cells, hemolytic anemia may ensue. Hemolysis may lead to hemoglobinuria hemoglobinuria /he·mo·glo·bin·uria/ (he?mo-glo?bi-nu´re-ah) free hemoglobin in the urine.hemoglobinu´ric

march hemoglobinuria  that seen after prolonged exercise.
, renal failure, and death. In rare cases, disseminated intravascular coagulation disseminated intravascular coagulation
n.
Abbr. DIC A hemorrhagic disorder that occurs following the uncontrolled activation of clotting factors and fibrinolytic enzymes throughout small blood vessels, resulting in tissue necrosis and
 and thrombocytopenia have occurred. (31)

The severity of systemic symptoms is directly proportional to the amount of envenomation but not to the severity of the skin lesion. (32) Patients who are in poor physical condition, the immunocompromised, the very young, and the elderly may experience serious systemic reactions. (2,5) At least 8 presumed deaths have been reported secondary to hemolysis, disseminated intravascular coagulation, renal failure, or pulmonary edema. (3)

When systemic signs occur, they do so in 72 to 96 hours? Our patient 3 began to manifest signs and symptoms of systemic loxoscelism after several days, but they were not formally addressed until 3 weeks after the bite. Sphingomyelinase D is believed to be the primary cause of systemic reactions because it can affect sphingomyelin sphingomyelin /sphin·go·my·elin/ (-mi´e-lin) any of the sphingolipids in which the head group is phosphorylated choline; they occur in membranes, primarily in nervous tissue, and accumulate abnormally in Niemann-Pick disease.  in many parts of the body, including the nerves, blood cells, and lungs.

Management of systemic reactions. Patients with systemic loxoscelism should have their complete blood count measured to look for evidence of thrombocytopenia, hemolysis, and leukocytosis Leukocytosis Definition

Leukocytosis is a condition characterized by an elevated number of white cells in the blood.
Description

Leukocytosis is a condition that affects all types of white blood cells.
. A high white blood cell count white blood cell count,
n a diagnostic clinical laboratory test to determine the number and types of leukocytes present in a measured sample of blood. Overall the normal number of leukocytes ranges from 5000 to 10,000/mm3.
 may indicate systemic involvement. A urinalysis should be performed to look for hemoglobinuria.

Patients suspected of having systemic loxoscelism may require hospitalization. In such cases, volume repletion re·ple·tion
n.
1. The condition of being fully supplied or completely filled.

2. A state of excessive fullness.
 should be maintained to promote a brisk urine output. (15) Transfusions of packed red cells packed red cells Transfusion medicine A concentrated unit of RBCs prepared from a unit of whole blood by removing plasma Indications Active bleeding, excess intraoperative blood loss, low 'pre-op' or 'post-op' Hcts, chronic anemias–eg, sickle cell anemia, , platelets, or plasma may be necessary. The use of steroids in these patients is controversial. One study indicated that prednisone, at a dose of 1 to 2 mg/kg/day for 2 to 4 days, may reduce hemolysis and protect the kidneys. (33)

References

(1.) Wilson DC, King LE, Jr. Spiders and spider bites. Darmatol Clin 1990;8:277-86.

(2.) Cacy J, Mold JW. The clinical characteristics of brown recluse spider bites treated by family physicians: An OKPRN Study. Oklahoma Physicians Research Network. J Fam Pract 1999;48:536-42.

(3.) Sams HH, King LE, Jr. Brown recluse spider bites. Dermatol Nurs 1999;11:427-33.

(4.) Hall RD, Anderson PC. Brown recluse spider bites: Can they be prevented? Mo Med 1981;78:243-4.

(5.) Bernstein B, Ehrlich F. Brown recluse spider bites. J Emerg Med 1986;4:457-62.

(6.) Forrester LJ, Barrett JT, Campbell BJ. Red blood cell red blood cell: see blood.  lysis induced by the venom of the brown recluse spider: The role of spbingomyelinase D. Arch Biochem Biophys 1978;187:355-65.

(7.) Rees RS, Nanney LB, Yates RA, King LE, Jr. Interaction of brown recluse spider venom on cell membranes: The inciting mechanism? J Invest Dermatol 1984;83:270-5.

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Granulocyte/macrophage colony stimulating factor (GM-CSF)
A substance produced by cells of the immune system that stimulates the attack upon foreign cells.
, IL-8, and E-selectin expression. J Clin Invest 1994;94:631-42.

(9.) Wright SW, Wrenn KD, Murray L, Seger D. Clinical presentation and outcome of brown recluse spider bite. Ann Emerg Med 1997;30: 28-32.

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(15.) Hobbs GD, Harrell RE, Jr. Brown recluse spider bites: A common cause of necrotic arachnidism. Am J Emerg Med 1989;7:309-12.

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(19.) Bernstein JE, Lorincz AL. Sulfonamides Sulfonamides Definition

Sulfonamides are medicines that prevent the growth of bacteria in the body.
Purpose

Sulfonamides are used to treat many kinds of infections caused by bacteria and certain other microorganisms.
 and sulfones in dermatologic therapy. Int J Dermatol 1981;20:81-8.

(20.) Rees RS, Altanbern DP, Lynch JB, King LE, Jr. Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision. Ann Surg 1985;202:659-63.

(21.) Rees R, Shack RB, Withers E, et al. Management of the brown recluse spider bite. Plast Reconstr Surg 1981;68:768-73.

(22.) King LE, Jr., Rees RS. Dapsone treatment of a brown recluse bite. JAMA 1983;250:648.

(23.) Rees R, Campbell D, Rieger E, King LE. The diagnosis and treatment of brown recluse spider bites. Ann Emerg Med 1987; 16:945-9.

(24.) Wesley RE, Ballinger WH, Close LW, Lay AM. Dapsone in the treatment of presumed brown recluse spider bite of the eyelid. Ophthalmic Surg 1985;16:116-17, 120.

(25.) Wille RC, Morrow JD. Case report: Dapsone hypersensitivity syndrome associated with treatment of the bite of a brown recluse spider. Am J Med Sci 1988;296:270-1.

(26.) Lang PG. Sulfones and sulfonamides in dermatology today. J Am Acad Dermatol 1979; 1:479-92.

(27.) Phillips S, Kohn M, Baker D, et al. Therapy of brown spider envenomation: A controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine cyproheptadine /cy·pro·hep·ta·dine/ (si?pro-hep´tah-den) an antihistamine with anticholinergic, sedative, and serotonin-blocking effects, used as the hydrochloride salt. It is also used in migraine prophylaxis. . Ann Emerg Med 1995;25:363-8.

(28.) Hollabaugh RS, Fernandes ET. Management of the brown recluse spider bite. J Pediatr Surg 1989;24:126-7.

(29.) Rees RS, Fields JP, King LE, Jr. Do brown recluse spider bites induce pyoderma gangrenosum? South Med J 1985;78:283-7.

(30.) Hoover EL, Williams W, Koger L, et al. Pseudoepitheliomatous hyperplasia and pyoderma gangrenosum after a brown recluse spider bite. South Med J 1990;83:243-6.

(31.) Arnold RE. Brown recluse spider bites: Five cases with a review of the literature. JACEP 1976;5:262-4.

(32.) Taylor EH, Denny WF. Hemolysis, renal failure and death, presumed secondary to bite of brown recluse spider. South Med J 1966;59: 1209-11.

(33.) Wasserman GS, Anderson PC. Loxoscelism and necrotic arachnidism. J Toxicol Clin Toxicol 1983-84;21:451-72.

From the Department of Otolaryngology--Head and Neck Surgery (Dr. Leach and Dr. Bassichis) and the Department of Ophthalmology (Dr. Itani), University of Texas Southwestern Medical Center, Dallas.

Reprint requests: Joseph Leach, MD, Department of Otolaryngology--Head and Neck Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390. Phone: (214) 648-2430; fax: (214) 648-9122; e-mail:joseph.leach @utsouthwestern.edu
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Author:Itani, Kamel
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