Hand-foot syndrome in a patient with multiple fire ant stings.

Abstract: The case is reported of an elderly patient with known previous exposure to fire ant stings, and who presented with hand-foot syndrome (HFS) in the setting of multiple fire ant stings to the lower extremities. Both hands and both feet were red, swollen, and mildly tender. Treatment was with fluocinonide cream, and all symptoms resolved as the classic fire ant skin lesions regressed. HFS was initially reported in association with acute crisis in sickle cell anemia and thalassemia and more recently as a common toxicity of chemotherapy administration. This is the first report of its occurrence in the setting of fire ant envenomization. Although recent literature may indicate a potential therapeutic benefit from COX-2 antagonists, the process appears to be self-limited, and requires only conservative treatment.

Key Words: envenomation, fire ant, hand-foot syndrome

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Imported fire ant infestation has been an increasing problem in the Southeast United States for the last seventy years. Three species are extant in this area, the most common being Solenopsis invicta, (1) and all of which share in common an aggressive nature and tendency to inject venom when disturbed. (2) The skin lesions associated with these stings are well described. (3,4) While the sting characteristically results in the formation of sterile pustules, complications due to infection can occur and are probably more common in patients with diabetes or other forms of immune suppression or debilitation. (3) Other reactions include anaphylaxis in patients with hypersensitivity, (5,6,7) and less commonly reported neurologic complications including seizures. (8) While most commonly occurring in the outdoors, multiple fire ant bites have been increasingly reported in long-term care facilities. (9,10) These are more likely to be multiple bites with higher complication rates. Herein is reported the case of an elderly male patient who presented with multiple fire ant bites and an associated hand-foot syndrome which cleared as the reaction to the bites subsided.

Case Report

A seventy-seven-year-old male with multiple medical problems was doing reasonably well until five days before presentation when he was bitten ten times on the right leg by fire ants. The next day he developed swelling and redness of the hands and feet. The erythema of the hands was primarily on the fingers and the webbing of the hands. Redness of the feet was on the plantar surface and extended onto the lateral surfaces. By day three his hands were improving but his feet remained red and somewhat painful. He presented in clinic on day five after the bites. The patient was on no new medications, but had suffered fire ant bites on several occasions in the past.

The patient's past medical history was positive for atherosclerotic cardiovascular disease, hypothyroidism, chronic obstructive pulmonary disease, hypertension, gastro-esophageal reflux disease, and he had received treatment for both prostatic and bladder cancer. His medications at the time of his fire ant exposure included the following: fexofenadine, antipyrene/benzocaine, ammonium lactate, naproxen, terazosin, simvastatin, sodium levothyroxine, aspirin, gemfibrozil, rabeprazole sodium, diltiazem, and nitroglycerin. None of these medications were new. Physical examination revealed a blood pressure of 131/63 mm Hg, height of 67 inches, weight of 176 pounds, respiratory rate of 20, pulse rate of 57, and temperature of 98.1[degrees]F. Ten circular lesions about 1 cm in diameter were noted on the anterior right lower leg. His hands appeared to be normal, but his feet were red and swollen with the process extending from the plantar surface onto medial ankle. The feet were minimally tender and there were no obvious puncture wounds or open sores. As per instructions from dermatology, the patient was treated with fluocinonide cream to affected areas. The hand and foot problems gradually resolved as the skin lesions associated with the fire ant venom healed. On his previously scheduled routine return to clinic, the patient voiced no other associated symptoms.

Discussion

The venom of fire ants contains very little protein (6,11) and is highly cross-reactive. (12) Both venom (6) and whole-body extracts (6,11) have been shown to have utility as skin test agents, and the whole-body extracts appear to be useful for hyposensitizing injections. (5,6,11,12) Due to cross-reactivity, venom extracts from S invicta may be adequate for diagnosis of any potential fire ant allergic reaction. Positive skin tests are probably IgE mediated (6) and hyposensitizing injections appear to reduce the risk of systemic reactions in individuals with positive skin tests. (5)

While most commonly associated with chemotherapy agent toxicity, palmar/plantar erythrodysesthesia (PPE) or hand-foot syndrome (HFS) was initially described in association with sickle cell [beta]-thalassemia (13,14,15) and subsequently with sickle cell crisis. (16,17) Occasionally the pain, redness, and swelling associated with the phenomenon masked, or at least delayed, the diagnosis of underlying Salmonella osteomyelitis. (18,19) The etiology or pathogenesis of the problem in sickle cell anemia has never been elucidated, and since the process resolved as the crisis abated, (17) no specific treatment was proposed.

The association of HFS with chemotherapy agents is common and well described. While most frequently reported in association with doxorubicin, cytarabine, docetaxel and fluorouracil, (20) HFS has been reported with multiple other agents including capecitabine, (21,22) vinorelbine (23,24) and the oral fluoropyrimidine TS-1 that is a combination of tegafur and uracil. (25,26) Histologic examination reveals scattered necrotic keratinocytes, vacuolar degeneration of the basal layer, and dilated blood vessels in the dermis. While the occurrence and incidence is known to be dose- and administration-dependent, (27) the exact pathogenesis remains obscure. It has been hypothesized that HFS is an inflammatory phenomenon mediated by over-expression of cyclooxygenase 2 (COX-2). (21) This hypothesis was supported by a retrospective analysis in which the COX-2 inhibitor celecoxib appeared to reduce the incidence of HFS in patients being treated with capecitabine. Reducing the agent dose or altering the administration schedule typically addresses HFS in association with chemotherapy. In addition to the suggested use of celecoxib, other reported therapies include elevation of the extremity, cold compresses, systemic corticosteroids, pyridoxine, and topical 99% dimethyl-sulfoxide. (20) Prophylaxis with dexamethasone appeared to alleviate the problem in a patient being treated with vinorelbine. (24) Since HFS toxicity is typically mild with chemotherapy, supportive care during treatment would appear to be the most appropriate approach in the absence of good evidence of effective therapy.

The human body experiences a powerful gravitational pull in the
direction of hope. That is why the patient's hopes are the physician's
secret weapon. They are hidden ingredients in any prescription.
--Norman Cousins

Accepted February 6, 2004.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9707-0707

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RELATED ARTICLE: Key Points

* Redness, swelling, and tenderness of both hands and feet characterize hand-foot syndrome (HFS).

* HFS can be associated with a variety of disease states such as sickle cell anemia, thalessemia, chemotherapy administration, and fire ant envenomization.

* In all settings, HFS appears to be self-limited and requires only removal or treatment of the inciting event.

COL Marcus E. Carr, MD, PHD, MC, USA

From the Department of Internal Medicine, Darnall Army Community Hospital, Ft. Hood, TX, and the Departments of Medicine and Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.

Reprint requests to M.E. Carr, Box 980230, Richmond, VA 23298-0230. Email: [e-mail]