University of Alabama at Birmingham

Gorgas Case 2016-07

Universidad Peruana Cayetano Heredia
The following patient was seen in the inpatient department of the 36-bed Tropical Disease Unit at Cayetano Heredia National Hospital in Lima, Perú.
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History: 42-year-old female transferred to our hospital with a 2-day history of a necrotic skin lesion and hematuria. While she was getting dressed, she felt a sudden stabbing pain on her right inner thigh, which increased up to a 10/10 intensity over the next 6 hours. She also noticed thigh erythema with a central violaceous discoloration in the affected area. Nausea, vomiting and a sensation of fever was present. The next day she noticed a red discoloration of her urine and decreased urine output. She denies abdominal pain, increased sweating or muscle contractions. No serous or purulent discharge from the skin lesion. No significant past medical history.

Epidemiology: Born in Ayacucho, in the Andean highlands and currently lives in Arequipa, Peru’s second largest city. The symptoms started while visiting her mother in Ayacucho, 12 hours away from Lima by road, where she stayed in an adobe house and slept on the ground.

Physical Examination: HR 96 RR 22 BP 110/60 SO2 96% Icteric sclera and skin. Chest: clear. CVS: normal. Abdomen: non-tender, no hepatosplenomegaly. Skin and Extremities: Painful necrotic eschars on right inner thigh surrounded by an extensive violaceous background, surrounded by a pale area, and an external erythematous halo (Image A). Swelling of the upper third of the thigh. No lymphadenopathy. Neurologic exam normal.

Laboratory Examination (on admission): Hb 7.9 g/dL, Hct 21%. WBC 23.2 (bands 0, neutrophils 92, monocytes 4, lymphocytes 4). Platelets 289 000 /mm3. PT 15.4, INR 1.32, PTT 33.6. Glucose 143 mg/dL, urea 153 mg/dL, creatinine 3.8 mg/dL, Na 135; K 5.2; Cl 108. Total bilirrubins 10.7 mg/dL: conjugated 8.3 mg/dL, unconjugated 2.4 mg/dL, Alk Phosphatase 31 U/L, AST 310 U/L (N<40), ALT 40 U/L, CK 435 U/L (N <170), LDH 16 321 U/L (N=140-280). Arterial blood gas: pH 7.22, pO2 65.4 mmHg, pCO2 27.4 mmHg, HCO3 11.0 mEq/L, SO2 92.6 %
Diagnosis: Necrotic aracnidism due to bite of the South American brown recluse spider Loxosceles laeta [Image B].
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Discussion: The diagnosis of loxoscelism is a clinical one though definitive criteria for the diagnosis require knowledgeable species identification of the offending spider. In this case, as soon as the patient felt the sudden pain, she immediately took her pants off and saw a 2cm brown spider with red colors on its abdomen run away. L. laeta are highly prevalent throughout much of coastal Peru and to a lesser extent in the highlands where this bite occurred. The spectrum of disease ranges from a mild skin irritation, to severe local necrotic reactions, to a less common syndrome (10-15% of cases), as in this patient, of viscerocutaneous loxoscelism manifested with vasoconstrictive blanching, sometimes a dengue-like scarlatiniform rash, hemolysis and renal failure. Mortality may uncommonly occur in severe cases and is higher in children due to lower body weight per amount of venom injected.

The classic “red, white and blue” sign, as seen here, is virtually diagnostic as the lesion evolves. The erythematous outer ring is vasodilatation, the middle white ring is vasoconstriction, and the central blue is pre-necrotic cyanosis early followed by actual necrosis. Other examples from our files provide instructive image of the typical evolution of the lesions (Cases 2015-01, 2008-03 and 2003-08). The patient often notes the initial bite, but it usually takes several hours for the onset of severe pain as the venom spreads. The violaceous central plaque represents an area of hemorrhage and thrombosis, which in more severe cases will progress to frank necrosis. Black-widow spiders (Lacrodectus sp) are also present in Peru but present without local necrosis and with parasympathetic hyperactivity including sweating, abdominal pain, and muscle contractions.

The bite of Loxosceles laeta is thought to cause more extensive and severe necrosis when compared to the related and well-studied brown recluse spider Loxosceles reclusa found in the United States and the venom is more lethal to mice when compared to venom from Brazilian L. laeta. The venom displays sphingomyelinase activity and produces dermonecrotic, hemorrhagic and edema effects when injected into rabbits (Guimaraes, G Toxicon 70 (2013) 90–97). When the lesions do evolve there is a hemorrhagic bulla, ulceration, and development of necrotic centers. The borders are irregular, influenced by gravitational factors (well shown here) as venom spreads in a manner related to the body part affected.

At least 54 species of Loxosceles are described from North and Central America and 30 species from South America, and additional species are found in Africa and the Mediterranean. Loxosceles laeta is native to Perú, Chile, Ecuador, Argentina, Uruguay, and south and eastern Brazil. It has been accidentally introduced into the U.S. and several Central American countries at various times but does not naturally thrive in those locations. Loxosceles laeta is similar in appearance to other recluse spiders but is generally larger with a body length up to 15 mm. The head region has dark violin shaped markings on the dorsal aspect [Image B] but these markings cannot be reliably used to identify recluses as other types of spiders may have similar markings.

Loxoscelism is a serious public health problem in Peru, with at least 2500 human bites per year. L. Laeta and to a lesser extent L. rufipes are the most medically important species in Peru. L. laeta is never seen in the jungle regions. They live most commonly in very domestic environments in both urban and rural areas, often hiding in clothing in drawers or in closets. They are not aggressive and only bite when disturbed or threatened. Bites occur more commonly in summer (January to April) when the spider reproduces and most bites occur at night or in the early morning.

Two commercial polyclonal equine antivenoms are produced one from CPPI, Brazil against Brazilian L. laeta, L. intermedia and L. gaucho and an antivenom produced by the Instituto Nacional de Salud del Perú (INS) containing antibodies against Peruvian L. laeta. Work in animal models has shown anti-venom to be effective if administered in the first 12 to 24 hours after a bite, but prospective controlled human clinical trials are lacking in any country [Toxicon. 2006 Aug;48(2):123-37]. Retrospective data is limited by lack of definition of time to antivenom administration and relation of that parameter to outcome. Our patient presented 2 days after the bite so antivenom was not considered. There is no commercial product available in North America. The commercial antivenoms efficiently inhibit the sphingomyelinase activity of both Peruvian and Brazilian L. laeta variants.

In Perú, as in many other countries that have various Loxosceles species, dapsone is sometimes administered at 100 mg/day for 1 week unless patients already have active hemolysis (excluding our patient) or are G6PD deficient. No controlled trials have been reported. G6PD deficiency does not occur in Perú. Systemic corticosteroids are often considered but again, no clinical trials support the practice.

Patients with any evidence of hemolysis or hemoglobinuria require vigorous intravenous hydration and urinary alkalinization to prevent renal failure. Aggressive debridement and escharectomy is advised but only once the acute phase is over; debridement too early may increase tissue loss.

Our patient was started on dialysis on the day of admission due to a decreased urine output (80 cc/12h). After hydration a CBC showed a Hb of 5.8 g/dL. She then developed respiratory insufficiency and was admitted to the ICU for ventilatory support, 5 units of packed red blood cells were administered but no inotropic support needed. As per protocol, she received antibiotic treatment with clindamycin and oxacillin for 7 days. On follow-up 2 months later serum creatinine was 0.9 mg/dL.