Continuing Education Activity

Of the nearly 165,000 Lepidoptera species found worldwide, only about 150 species cause significant envenomations, with about 50 species found in the United States. Lepidoptera is the order of insects that includes butterflies, moths, and caterpillars. Several caterpillars (the larval form of butterflies and moths) contain spines or urticating hairs that secrete a toxin, causing skin manifestations such as localized pain, edema, and erythema. Some caterpillar species can cause severe injuries, including allergic reactions, consumptive coagulopathy, intracranial hemorrhage, acute kidney injury, ataxia, dysarthria, arthritis, joint deformities, wheezing, and dyspnea. The puss moth caterpillar (Megalopyge opercularis) is considered one of the most toxic in North America and is responsible for hundreds of human envenomations annually. Lonomia obliqua caterpillars found in South America, especially in Brazil, are infamous for causing severe pain and hemorrhagic syndrome. Contrastingly, the Anaphe venata caterpillar in Nigeria is an essential protein resource from a cultural-specific diet and can cause thiamine deficiency syndrome similar to dry beriberi.

This CME course is designed to empower healthcare professionals with a profound understanding of Lepidoptera envenomations, a niche yet critical aspect of vector-borne emergencies. Despite the vast diversity of Lepidoptera species globally, only a fraction poses a significant threat to human health. This course aims to bridge the gap surrounding these envenomations' clinical manifestations, etiology, and management, ensuring clinicians cannavigate these unique challenges. Through participation in this activity, learners will be adept at identifying Lepidoptera envenomations, differentiating between toxic species, and implementing evidence-based management strategies. The interprofessional approach ensures that clinicians, nurses, and other healthcare professionals collaborate seamlessly, ultimately improving patient outcomes and reducing the long-term impact of these unique vector-borne emergencies. 

Objectives:

• Identify the signs and symptoms of Lepidoptera envenomations.

• Implement the appropriate management of Lepidoptera envenomations. 

• Differentiate the pathophysiology of envenomations in each Lepidoptera species.

• Collaborate with all members of the interprofessional team, including the medical toxicologist a the regional poison control center, to provide efficient, comprehensive, and coordinated care.

Introduction

Lepidoptera is an order of insects that includes butterflies, moths, and caterpillars. Several caterpillars (the larval form of butterflies and moths) found worldwide contain spines or urticating hairs that secrete a toxin, irritating humans upon contact.[1] Skin manifestations such as localized pain, edema, and erythema comprise most clinical presentations of Lepidoptera envenomation.[2][3] However, some caterpillar species can cause severe injuries, including allergic reactions, consumptive coagulopathy, intracranial hemorrhage (ICH), acute kidney injury (AKI), ataxia, dysarthria, arthritis, joint deformities, wheezing, and dyspnea.[4][3][5]

"Lepidopterism" (derived from the Greek words lepis, meaning scale, and pteron, meaning wing) refers to the various skin and systemic reactions secondary to human contact with moths and butterflies.[5] "Erucism" (derived from the Latin word eruca, meaning caterpillar) refers to cutaneous dermatitis resulting from contact with caterpillars with urticating hairs.[5][6] 

More than 50 species of caterpillars are venomous in the US. The puss moth caterpillar (Megalopyge opercularis) is considered one of the most toxic in North America and causes hundreds of human envenomations annually.[7][8] Other common names include asp, tree asp, Italian asp, wooly asp, opossum bug, wooly slug, and "el perrito."[7] The puss caterpillar is found in the southeast and south-central US (particularly Texas, Louisiana, and Florida) and is abundant during the late spring (June-July) through the early fall season (September-October).[9][10] The species is often found in trees and shrubbery around homes, schools, and parks.[7] The typical physical characteristics include a teardrop-shaped furry body with silky tan to brownish hairs.[9] Beneath this furry coat are short hollow spines attached to a venom sac that discharges upon contact.[3][11] The color of the spines ranges from white, grey, tan, or yellow to reddish-brown.[12][1]  

Other notable venomous caterpillars in the US include the flannel moth (Megalopyge crispata), the lo moth (Automeris io), the saddleback moth (Acharia stimulata), and the hickory tiger moth (Lophocampa caryae).[2][13] Lonomia obliqua caterpillars in South America, especially in Brazil, are infamous for causing severe pain and hemorrhagic syndrome.[14][15] In Australia, caterpillars such as the mistletoe brown-tail moth (Euproctis edwardsi), processionary caterpillars (Ochrogaster lunifer), cup moths (Doratifera spp.), and the white-stemmed gum moth (Chelepteryx collesi) are of medical importance.[16] Pine processionary caterpillars (Thaumetopoea pityocampa) are the important defoliator of pine forests in the Mediterranean and central European countries, with significant economic and occupational consequences for workers in these forests.[17] The Anaphe venata caterpillar in Nigeria is an essential protein resource but can cause thiamine deficiency syndrome similar to dry beriberi.[18][19] Additionally, dendrolimus caterpillars in China and Preolis semirufa caterpillars in Brazil are linked to significant joint disease.[20][4]

Etiology

Caterpillars, rather than adult butterflies and moths, cause most cases of lepidopterism and erucism.[3][21] Envenomation occurs by physical contact with a caterpillar's setae, hairlike hollow structures connected to a single basal poison gland or secretory epithelial cells. Venom accumulates and is stored in the setae and may fracture and release venom upon physical contact.[12]  Setae may be embedded into the skin or mucous membranes, resulting in an irritant reaction distinct from a venomous reaction.[22] Certain species of moths also contain setae or spines.[5] However, most adult species lose their irritating setae when they emerge from their cocoons and become relatively harmless. Some caterpillar species do not produce venom.

Eye exposure of either hemolymph and setae results in acute scleritis or ophthalmia nodosa; this manifests as simple conjunctivitis and progresses into a more severe panophthalmitis when setae penetrate the cornea.[23] In rare cases, cataracts may develop.[24] Reactions are mostly from the toxic effects of the setae/hemolymph or immunoglobulin E (IgE) production that results in a hypersensitive state and manifests as a type IV (T-cell-mediated) hypersensitivity reaction, usually from direct contact.[25] Other vectors include airborne transmission spread by wind or carried on pets and other natural objects.[26]

Epidemiology

Although Lepidoptera are worldwide, only a few species cause harmful human reactions. In 2021, the Annual Report of the National Poison Data Systems from America's Poison Control reported 1014 caterpillar exposure cases.[27] Most exposures were accidental, with 47% of cases occurring in adults 20 years or older and 35% in children 12 years or younger.[27]  Being naturally curious, children are at a somewhat increased risk of exposure.[22] Cases are more numerous among men than women. There were no reported deaths due to caterpillar exposures.[27] However, the actual number of cases and adverse reactions are likely underestimated due to underreporting, as most exposures are mild and self-limiting. 

Exposures to caterpillar stings are usually unintentional and vary depending on the region and season.[26] Occupations requiring climbing trees or working closely with plants are risk factors in adults. In Brazil, the Premolis semirufa caterpillar (natively called pararama) is of significant concern as an occupational disease for rubber tappers (harvesters of latex from rubber trees).[2] Setae disperses through the air, particularly in regions where indigenous species molt—leading to multiple exposures, especially during seasons of abundance.[28]

Spring or summer can result in a spike in cases about school recess, camping/hiking, logging activity, or landscaping.[26][9] Ophthalmia nodosa is a seasonal disease due to the preponderance of caterpillars during the autumn months (August-October). However, the exact incidence of the disease is unknown.[29]  

Pathophysiology

Caterpillars and their toxins have not been thoroughly investigated, except the Premolis semirufa of Brazil, South American Lonomia, and Thaumetopoea pityocampa.

Dendrolimiasis describes urticarial dermatitis and joint symptoms resulting from exposure to the Dendrolimus species caterpillar of China and Preolis semirufa caterpillars of Brazil.[28] The Premolis semirufa caterpillar is of significant concern as an occupational disease for rubber tappers (harvesters of latex from rubber trees) in Brazil. The venom contains formaldehyde and uncharacterized histamine analogs with a tropism for receptors in the bones, joints, and cartilage. During the acute phase of envenomation, there is a strong inflammatory response that is IgE-mediated.[30] Frequent unintentional exposures lead to chronic symptoms, featuring synovial membrane thickening, joint deformities, and chronic mono or oligoarticular synovitis. This chronic bone and joint disease is believed to be autoimmune-mediated and is called pararamose.[30]  

The hickory tussock moth (Lophocampa caryae) located in North America produces a histamine reaction upon human contact. The toxin's exact mechanism and chemical composition are not fully elucidated.[31] Similarly, the pine processionary caterpillar (Thaumetopoea pityocampa) possesses a toxin called thaumetopoein that also causes a histamine reaction.[32][33]

Ophthalmia nodosa is a rare but well-documented ocular disease caused by a reaction to embedded urticarial hairs of several arthropods, including caterpillars, moths, and tarantulas.[34] This disease initially produces conjunctivitis with subsequent panuveitis due to corneal penetration and intraocular migration of urticating hairs or setae.[35][36][37][38][39] The conjunctiva and iris subsequently form granulomatous nodules in response to the caterpillar hairs or setae. The clinical effects depend on the initial injury force, the effect of the urticating toxin, and the intraocular locomotion of the hair or setae. Constant iris movement, respirations, and pulsations are thought to propel the hairs or setae. Listed below is a practical classification scheme for the disease created by Cadera et al.[40]

Classification of Ophthalmia Nodosa (Cadera et al)

Type 1: An immediate response to the hair involving chemosis and inflammation for several weeks.

Type 2: The presence of hairs embedded in the bulbar or palpebral conjunctiva causing chronic mechanical keratoconjunctivitis, resulting in a foreign body sensation and linear corneal abrasions.

Type 3: Grey-yellow granulomatous nodules may form in the conjunctiva due to subconjunctival or intracorneal setae. These nodules may be asymptomatic.

Type 4: Hair penetration of the anterior eye segment may lead to iritis as a secondary complication.

Type 5: Involvement of the vitreoretinal region may occur when hairs penetrate the posterior segment via the anterior chamber or transscleral, which may take several years to manifest. The effects can vary from mild vitritis with or without cystoid macular edema to severe endophthalmitis.[34][40][36]

Lonomism is a severe hemorrhagic disease caused by envenomation of the Lonomia species.[2] The disease is characterized by a syndrome of consumptive coagulopathy and fibrinolysis secondary to the venom, the proteolytic enzyme lonomin V found in the hairs, spines, and hemolymph of the Lonomia species caterpillars (Lonomia obliqua, Lonomia achelous). Lonomin V activates factor X, factor II (prothrombin), and collagen degradation, leading to platelet inhibition.[2] Suggested mechanisms of toxin-mediated AKI are dilation of Bowman capsule and increased permeability of the tuft capillaries, resulting in the deposition of fibrinolytic compounds and initiating the conditions for acute tubular necrosis (ATN).[41] Systemic lonomism manifests as a consultive coagulopathy with secondary fibrinolysis, although most deaths result from acute kidney injury.[42] 

The venoms of both Lonomia species provoke similar clinical effects with different mechanisms of action.[43] The L obliqua venom is mediated mainly by thrombin formation secondary to procoagulant toxins at different levels of the coagulation cascade, as opposed to the L achelous venom, which activates both fibrinolysis and clotting pathways resulting in mild disseminated intravascular coagulation (DIC).[44] Factor XIII is drastically reduced in L achelous envenomated patients due to a factor XIII degradation component in the venom. However, the L obliqua venom contains a factor X activator called Losac (Lonomia obliqua Stuart factor activator) and a prothrombin activator called Lopap (Lonomia obliqua prothrombin activator protease).[45][46] Results from studies have suggested that a combination of DIC due to thrombin formation, intravascular fibrin formation, and secondary activation of the fibrinolytic syndrome are responsible for L obliqua hemorrhagic syndrome.[47] The difference in hemorrhagic syndrome prodrome between the 2 species plays a vital role in the treatment.[48][44]

Seasonal ataxia is a clinical syndrome of acute cerebellar ataxia, nausea, and vomiting. This condition has been implicated in epidemics in western Nigeria during the 1950s, caused by consuming the African silkworm (Anapha venata) for protein.[49][18][50][51] Coinciding with the rainy season (July-October), the larvae are abundantly found in local markets and frequently consumed with high carbohydrate-based foods, which contain thiamine-binding cyanogenetic glycosides.[51] However, the larvae of the Anapha venata contain heat-resistant thiaminases that exacerbate the thiamine-deficient population.[49] 

Histopathology

Controlled studies involving injecting venom from Lonomia species into laboratory rats demonstrate histopathologic changes consistent with ATN. Specifically, increased acidophilia, dilation of renal tubules, loss of proximal brush border, cytoplasm vacuolation, nuclear pyknosis, and desquamation of necrotic cells.[41] Continuing research is underway for other caterpillar species and their venom.

Toxicokinetics

Toxicologic studies of caterpillar venom are most prevalent in the toxicology and dermatology literature; however, more studies are necessary for a complete understanding. Current research has found that Lepidoptera venom contains peptides, hyaluronidase, phospholipase A, and bioamines such as histamine (or histamine-releasing substances).[2]

History and Physical

Caterpillar exposures can be categorized into 2 types: stinging reactions and pruritic reactions, although there may be some overlap.[28] Stinging caterpillars possess hollow spines that release venom upon contact. The stinging reaction is characterized by a painful burning sensation with local and rarely systemic effects. The affected area becomes swollen and erythematous and may develop papules and vesicles. A gridlike pattern rash may develop within 2 to 3 hours of exposure. Certain species leave pathognomonic skin patterns, such as an "M" shape seen with opercularis stings, often with a gridlike pattern matching the caterpillar's spine distribution.[2] Associated systemic symptoms may also include nausea, vomiting, fever, headache, restlessness, tachycardia, hypotension, urticaria, seizures, lymphadenitis, and local adenopathy.

On the other hand, exposure to itchy caterpillars with non-venomous urticating hairs can lead to pruritic reactions. These reactions can result from mechanical irritation, an allergic reaction, or a granulomatous reaction due to the chronic presence of the hairs.[4] The Ochrogaster lunifer of Australia is known to cause intense pruritic dermatitis. Allergic reactions, dermatitis, and anaphylaxis are associated with the Thaumetopoea pityocampa of Asia, North Africa, and Europe.

Dendrolimiasis is a chronic form of lepidopterism caused by direct contact with the central Asian pine tree lappet caterpillar (Dendrolimus sp) found in China. The clinical effects of this condition include maculopapular dermatitis, inflammatory migratory polyarthritis and polychondritis, chronic osteoarthritis, and rarely acute scleritis. Associated symptoms include fever, anorexia, fatigue, chills, headaches, and dizziness.[52] 

Pararamose is a similar disease to dendrolimiasis and is associated with direct contact with the Premolis semirufa caterpillar of Brazil.[2] This is a significant occupational hazard for rubber tree plantation workers in the Brazilian Amazon rainforest. The clinical effects are similar to dendrolimiasis and include painful/pruritic dermatitis associated with painful arthritis and joint deformities after repeated exposures to the caterpillar. 

A hemorrhagic syndrome characterized by a consumptive coagulopathy and secondary fibrinolysis is associated with the South American Lonomia sp caterpillars in Brazil, Venezuela, and northern Argentina.[2] Of the 26 Lonomia species, only 2 are known to cause a severe coagulation disorder: the Lonomia obliqua, located in Southern Brazil, and the Lonomia achelous, located in Venezuela and Northern Brazil.[53] Both species result in a consumptive coagulopathy similar to disseminated intravascular coagulation (DIC). High fatality rates occur from pulmonary and intracerebral hemorrhage with acute renal failure due to the venom's nephrotoxicity and microcirculatory fibrin deposition.[43] The first symptoms after contact include intense burning, erythema, edema, heat, and blistering. Consumptive coagulopathy can occur at 6 to 72 hours after envenomation; however, this may occur within 4 to 6 hours after contact with L obliqua.[54] 

Evaluation

Laboratory or imaging studies are not required for most caterpillar envenomations limited to the skin. 

The following studies should be considered for Lepidoptera envenomations according to the corresponding species syndrome:

• Complete blood count 
• Coagulation studies (prothrombin time, activated partial thromboplastin time, fibrinogen level, fibrin degradation products, and D-dimer)
• Basic metabolic panel (specifically BUN and creatinine)
• Urinalysis to evaluate for blood and protein
• Chest radiography if significant respiratory symptoms are present
• Electrocardiogram for tachycardia or dysrhythmias
• Slit-lamp examination for ophthalmic exposures
• Fluorescence stain of the affected eye to rule out corneal abrasions

Treatment / Management

Supportive management for dermal Lepidoptera envenomation involves washing affected areas with soap and water and contactless drying using a hair dryer or fan. Careful application of adhesive tape at the bite site will assist in removing hairs.[7] Any constricting clothing or jewelry, such as rings, should be removed in anticipation of swelling of the affected extremity. Applying topical isopropyl alcohol and an ice pack accomplishes cooling measures. It is advisable to recommend tetanus prophylaxis. 

Recommend urgent ophthalmologic consultation for any caterpillar-related eye exposures, typically for type 1 or 2 ophthalmia nodosa classifications. Ocular exposures should undergo irrigation with copious amounts of 0.9% sodium chloride solution. Administration of a topical ophthalmic anesthetic will significantly ease eye pain and facilitate examination and treatment. Examining the fornix of the eye for hairs with double eversion is essential. Slit-lamp examination of the affected eye includes fluorescein staining to determine the presence of corneal abrasions. Under a microscope, carefully remove caterpillar hairs using forceps or a 26-gauge hypodermic needle. After removal of the hairs, treatment includes topical steroids, cycloplegics, lubricants, and antibiotics.[55][56] 

In type 3 lesions, surgical excision of granulomatous nodules by an ophthalmologist may be necessary. Type 4 lesions require topical steroids and may include iridectomy for the removal of nodules and hairs. Type 5 lesions may consist of both topical and systemic steroids, with resistant cases requiring vitrectomy for the removal of venomous hairs.[29]

Control pain control by administering topical anesthetics, minor analgesics, and opioids. Applying topical steroids will reduce conjunctival chemosis and lid edema and help with the eye examination. Manage cutaneous symptoms such as pruritus and urticaria with oral antihistamines. Treat respiratory symptoms with nebulized beta-agonists and systemic steroids. Anaphylaxis and severe respiratory symptoms may require intramuscular epinephrine and systemic steroids.The management of dendrolimiasis is primarily with supportive care. Recommend prompt surgery to remove sinus tracts and the affected cartilage to prevent permanent bone and joint deformities. Managing the hemorrhagic syndrome caused by exposure to the L obliqua caterpillar includes administering clotting factors, platelets, and cryoprecipitate.[46] The antidote for this syndrome is available in Brazil and is called antilonomic serum (SALon).[57][48] 

Consulting a hematologist for suspected Lonomia envenomation is essential, as the management L obliqua and L achelous are different.[46] Treatments such as cryoprecipitate, purified fibrinogen, and antifibrinolytics (aprotinin and ε-aminocaproic acid) have proven beneficial for L achelous envenomations. In contrast, this transfusion regimen could potentially worsen the bleeding syndrome in cases of L obliqua envenomation and can be fatal. Recommend that patients envenomated by either species avoid receiving whole blood or fresh plasma transfusions, as these can exacerbate the hemorrhagic syndrome.[46]For those suffering from seasonal ataxia caused by the African silkworm (Anapha venata), supportive care and 100 mg of oral thiamine every 8 hours have been shown to reduce the symptoms within 2 days.[58] Consultation with a medical toxicologist or regional poison control center for any caterpillar envenomation for treatment guidance is also recommended.

Differential Diagnosis

The differential for Lepidoptera envenomations include the following:

1. Dermatitis (Atopic, allergic, and contact)
2. Allergic reaction
3. Arthropod envenomations (Insect bites, centipede, millipede, scorpion, tarantula, black widow spider, and brown recluse)
4. Corneal abrasions and ulcers from retained foreign bodies
5. Toxicodendron poisoning 
6. Henoch Schonlein purpura (HSP) or IgA Vasculitis
7. Idiopathic thrombocytopenic purpura (ITP)
8. Iritis and uveitis

Prognosis

The prognosis for Lepidoptera envenomation is excellent, except for complicated ocular exposures and persistent systemic symptoms. With appropriate ophthalmologic or other specialty care in a tertiary referral hospital, a full recovery is expected. There are rare reports of deaths due to caterpillar envenomation, but these are usually the result of inadequate medical attention or exposure in austere locations.

Complications

The range of complications for caterpillar hair eye exposures depends on the penetration and effect of the urticating toxins. Brief exposures to the hairs may result in conjunctival chemosis, corneal abrasions, lid edema, and a foreign body sensation that may last for weeks. Additional complications range from chronic keratoconjunctivitis, corneal granulomas, chronic scleritis, iritis, and uveitis to cataract formation and impaired vision.[36] Systemic lonomism usually results in self-limited coagulopathy and renal impairment with the possibility of chronic renal insufficiency in some cases. 

Consultations

Consultations for butterfly, moth, and caterpillar envenomations include the following:

• Medical toxicology or your regional poison control center for any caterpillar envenomations
• Ophthalmology for urticating hair eye exposures
• Hematology for Lonomia envenomations

Deterrence and Patient Education

Educating the general public is essential for preventing caterpillar envenomations. Teaching children caterpillars should not be touched may prevent most unintentional exposures. Prudence dictates avoiding areas infested with caterpillars. A heightened level of awareness is essential during peak caterpillar seasons, such as spring/summer, especially in endemic areas. When outdoors, protective gear such as eye protection, long-sleeved shirts, long pants tucked into socks, work gloves, and a wide-brimmed hat may prevent envenomation upon unintentional contact with a caterpillar. Removing a caterpillar on the skin with a stick or tool rather than bare hands can prevent additional exposure to venom. 

Pearls and Other Issues

Become familiar with the local/regional toxic caterpillars. Many websites aimed at the layperson are helpful, with descriptions and high-resolution photographs. 

Enhancing Healthcare Team Outcomes

Prevention is the best approach to caterpillar envenomations. To prevent exposure, the healthcare team, including doctors, nurses, and pharmacists, should work toward teaching children and outdoor workers to identify these vectors. Everyone playing or working outdoors in endemic areas should have a heightened level of alertness during peak caterpillar seasons (spring/summer). Encourage patients to wear protective clothing. Clothing should include long-sleeved shirts, long pants tucked into socks, work gloves, and a wide-brimmed hat to minimize the likelihood of accidental exposure; further, using a tight-fitting respirator mask and eye protection can help ensure a secure work zone in known heavily infested areas.