Envenomation by Aquatic Invertebrates

Chapter 80 Envenomation by Aquatic Invertebrates

For online-only figures, please go to www.expertconsult.com image

Stinging aquatic animals pose a hazard for swimmers and divers. They constitute a large collection of marine organisms that include invertebrates and vertebrates, and that range from primitive to extremely sophisticated organisms. This chapter discusses envenomation by aquatic invertebrate life-forms. Chapter 81 discusses envenomation by aquatic vertebrate life-forms. Chapter 79 discusses infections associated with aquatic wounds and the relevant antimicrobial therapies. Standard wound care measures, such as antitetanus immunization, should be undertaken whenever there is penetration of the skin.

The science of poisons, biotoxicology, is divided into plant poisons, or phytotoxicology, and animal poisons, or zootoxicology. Toxinology connotes the science of toxic substances produced by or accumulated in living organisms, their properties, and their biologic significance for the organisms involved.130 Animals in which a definite venom apparatus is present are sometimes called phanerotoxic, whereas animals whose body tissues are toxic are termed cryptotoxic.164 Naturally occurring aquatic zootoxins may be designated as oral toxins (which are poisonous to eat and include bacterial poisons and products of decomposition), parenteral toxins (venom produced in specialized glands and injected mechanically [by spine, needle, fang, fin, or dart]), and crinotoxins (venom produced in specialized glands and administered as slime, mucus, or gastric secretion). Within these three subdivisions, further classifications are by phylogeny, chemical structure, and clinical syndrome.

Although all venoms are poisons, not all poisons are venoms. Venoms can be released in varying amounts and have evolved for conquest and defense. It is theorized that offensive (prey capture and digestion) venoms are generally perioral (mouth, fang, or tentacle) and that defensive venoms are aboral (tail and sting) or dermal (barb and secretion). In the evolutionary scheme, it appears that many venomous fish seek specific self-defense, whereas poisonous fish are noxious in a nonspecific manner.7 A brief comparison of the features of venoms and poisons shows that, generally, poisons produced in skin, muscle, blood, or organs are heat (46° to 49° C [115° to 120° F]) and gastric acid stable and carry seasonal toxicity. They are not “released,” and they may lack a well-defined biologic function. Venoms are more commonly heat labile, gastric acid labile, and nonseasonal in toxicity.

In snakes, the latency, toxicity, and duration of venom effects are related to the route of envenomation. Intravascular injection is significantly more lethal than intraperitoneal or transcutaneous injection, as determined by the dose that produces 50% lethality in a group (LD50). This principle is not commonly applied to marine venoms because few encounters involve direct intravascular injection.

Most venoms are high-molecular-weight amalgams of vasoactive amines, proteolytic enzymes, and other biogenic compounds. These substances denature membranes, catabolize cyclic 3′,5′-adenosine monophosphate, degranulate mast cells, provoke histamine release, initiate arachidonate metabolism, accelerate coagulopathy, interfere with cellular transport mechanisms, disrupt metabolic pathways, impede neuronal transmission, and evoke anaphylaxis and shock. Toxin-containing venoms from marine and other creatures include components, such as incretin mimetics, sarafotoxins, antiarrhythmics, and bradykinin-potentiating and natriuretic peptides, that may be applicable to cardiovascular drug discovery.85 Although many marine venoms are composed of protein and polypeptide subunits, they lack sufficient immunogenicity to allow development of antitoxins or antivenoms. Poisons represent metabolic by-products and are usually of smaller molecular weights.

Taxonomy of marine animals can sometimes be confusing. The hierarchy, in descending order, is kingdom, phylum, class, order, family, genus, and species.

Treatment recommendations are constantly evolving in response to acquisition of data, clinical observations, and preferences of expert rescuers and physicians.

Allergic Reactions


An envenomation or the administration of antivenom can elicit an allergic reaction. In the previously sensitized individual, the antigen (venom, aquatic protein, or animal serum) complexes with immunoglobulin E (IgE) and perhaps with IgG homocytotropic antibodies or activated complement cleavage products attached to the membranes of mast cells and basophils. This induces membrane permeability, which allows degranulation or membrane production of histamine, serotonin, kinins, prostaglandins, platelet-activating factor, eosinophil and neutrophil chemotactic factors, leukotrienes, and other bioactive chemical mediators.9

The signs and symptoms of anaphylaxis may occur within minutes of exposure. They include hypotension, bronchospasm, tongue and lip swelling, laryngeal edema, pulmonary edema, seizures, cardiac arrhythmia, pruritus, urticaria, angioedema, rhinitis, conjunctivitis, nausea, vomiting, diarrhea, abdominal pain, gastrointestinal bleeding, and syncope. Most severe allergic reactions occur within 15 to 30 minutes of envenomation, and nearly all occur within 6 hours. Fatalities are often related to airway obstruction or hypotension. Acute elevated pulmonary vascular resistance may contribute to hypotension that results from generalized arterial vasodilation.10,12


Decisive treatment should be instituted at the first indication of hypersensitivity. Specific treatment recommendations for anaphylaxis are found in Box 62-3.

Antivenom Administration

A number of marine envenomations, such as those by the box-jellyfish and certain sea snakes, may provoke the administration of specific antivenom by the treating clinician. Marine antivenoms are raised in horses or sheep and therefore may be antigenic in humans, inducing both immediate and delayed hypersensitivity. Most authorities recommend that a skin test be performed for sensitivity to horse serum, if the clinical situation permits, after a sea snake envenomation. A skin test should be done only after deciding to administer antivenom; it is not done to determine whether antivenom is necessary. The purpose of sensitivity testing is to allow adequate prophylaxis against anaphylaxis. The skin test is performed with an intradermal injection into the upper extremity of 0.02 mL of a 1 : 10 dilution of horse serum test material in saline, with 0.02 mL saline in the opposite extremity as a control. Erythema and a wheal with pseudopodia appear in 15 to 30 minutes in a positive response. Because antivenom contains many times the protein content of horse serum used for skin testing, the use of antivenom for skin testing may increase the risk of anaphylactic reaction. If the skin test is positive, the antivenom intended for intravenous (IV) infusion should be diluted in sterile water to a 1 : 100 concentration for administration. Successive vials should be less dilute if the allergic reaction is minimal (controlled by antihistamines and epinephrine). A negative skin test does not preclude the possibility of an anaphylactic response to antivenom administration.

The rationale for administering antivenom is to provide early and adequate neutralization of the toxin at the tissue site of entry before it gains systemic dominance. Except for stonefish antivenom, the product is preferentially administered intravenously, taking care to provide adequate doses for children and older adults, who have a decreased volume of distribution and increased sensitivity to venom effects. The antivenom intended for IV administration should always be diluted with normal saline, Ringer’s lactate, or dextrose 5% in water.

Marine antivenoms are produced and distributed in the Indo-Pacific regions. They include the following:

A person who is known to be sensitive to horse or sheep serum, has a positive skin test, or develops signs of an allergic reaction or anaphylaxis during antivenom therapy requires aggressive medical management. A recipient of antivenom should be pretreated with 50 to 100 mg of IV diphenhydramine (1 mg/kg in children). After this, the initial dose of antivenom is administered at a rate no faster than one vial each 5 minutes. If no allergic manifestation ensues, the antivenom can be administered at a more rapid rate. If signs of anaphylaxis develop, usually heralded by an urticarial eruption or pruritus, 0.1- to 0.2-mL aliquots of antivenom should be alternated with 3- to 10-mL (0.03 to 0.1-mg) IV doses of aqueous epinephrine 1 : 100,000 (infused over 5 to 10 minutes). Alternatively, an epinephrine drip may be prepared as discussed in Chapter 62. The victim should be managed in an intensive care unit, with electrocardiographic and blood pressure monitoring. The dose of epinephrine should not elevate the pulse rate to greater than 150 beats/min. The administration of IV epinephrine may cause transient hypokalemia as potassium is driven intracellularly; cessation of the epinephrine infusion may create transient hyperkalemia as the potassium regains entry into the extracellular space. If a victim is highly allergic to antivenom, serious consideration should be given to supportive therapy (including hemodialysis) without antivenom administration.

In one series, stonefish antivenom was administered to 24 victims in a dose of one or two ampules by the intramuscular (IM) route, without any “immediate reactions” reported.189 In this same report, six victims received box-jellyfish antivenom by the IV route without immediate or delayed reactions. Anecdotal reports indicate that box-jellyfish antivenom has been administered by the IM route in the field more than 80 times to date without any episode of anaphylaxis.

Serum Sickness

The formation of IgG antibodies in response to antigens present in antivenom (prepared in heterologous serum) results in the deposition of immune complexes in many tissue sites, notably in the walls of blood vessels. These complexes induce vascular permeability, activate the complement cascade and chemotactic factors, degranulate mast cells, and trigger the release of proteolytic enzymes. Decreased levels of C3 and C4 are accompanied by increased C3a/C3a des-arginine, a split product C3.69,105 Although immune complexes can be measured by various tests (Raji-cell IgG assay and C1q-binding assay), levels of immune complexes may not correlate with the clinical presentation.69,138 Cutaneous venulitis may precede vasculitis. Dermal biopsy of lesional skin may reveal leukocytoclastic vasculitis.

Symptoms are generally present within 8 to 24 days and include fever, arthralgias, malaise, urticaria, lymphadenopathy, urticarial and morbilliform skin rashes, peripheral neuritis, and swollen joints. It is not uncommon for the primary urticarial lesion to be noted at the injection site. Serum sickness is managed with the administration of corticosteroids. An initial loading dose of prednisone (40-60 mg for adults, and 2 to 5 mg/kg, not to exceed 50 mg, for children) should be administered and maintained daily until symptoms markedly resolve. The corticosteroid should be tapered over a 2- to 3-week course to avoid induction of adrenal insufficiency. Aspirin or other nonsteroidal antiinflammatory agents are rarely helpful and may be contraindicated because of circulating immune complex–induced platelet dysfunction.

Sponges (Phylum Porifera)

Life and Habits

There are approximately 5000 species of sponges (phylum Porifera, predominantly of class Desmospongiae), which are supported by horny, but elastic, internal collagenous skeletons of spongin, some forms of which we use as bath sponges. Sponges are without digestive, excretory, respiratory, endocrine, circulatory, and nervous systems. Embedded in the connective tissue matrices and skeletons are spicules of silicon dioxide (silica) or calcium carbonate (calcite), by which some sponges can be definitively identified. In general, sponges are stationary acellular animals that attach to the sea floor or coral beds and may be colonized by other sponges, hydrozoans, mollusks, coelenterates, annelids, crustaceans, echinoderms, fish, and algae. These secondary coelenterate inhabitants are responsible for the dermatitis and local necrotic skin reaction termed sponge diver’s disease (maladie des plongeurs).183 In recognition of a medicinal property, the ancient Greeks burned sea sponges and inhaled the vapors for prophylaxis against goiter.46 Sponges harbor various biodynamic substances, with possible antineoplastic, antibacterial, growth-stimulating, antihypertensive, neuropharmacologic, psychopharmacologic, and antifungal properties. A number of sponges produce crinotoxins that may be direct dermal irritants, such as subcritine, halitoxin (Haliclona species), p-hydroxybenzaldehyde, and okadaic acid. These may be present in surface or internal secretions. Murine monoclonal antibodies against okadaic acid intended for use in an assay system for the detection of diarrhetic shellfish poisoning have been prepared from the sponge Halichondria okadai.199 The causative agent of Dogger Bank itch, (2-hydroxyethyl) dimethylsulfoxonium chloride, has been isolated from the marine sponge Theonella aff. mirabilis.205

Clinical Aspects

Two general syndromes, with variations, are induced by contact with sponges. The first is a pruritic dermatitis similar to plant-induced allergic dermatitis, although the dermatopathic agent has not been identified. Rarely, erythema multiforme or an anaphylactoid reaction may be present. A typical offender is the friable Hawaiian (Figure 80-1) or West Indian fire sponge (Tedania ignis), a brilliant yellow-vermilion-orange (Figure 80-2) or reddish-brown organism with a crumb-of-bread appearance found off the Hawaiian Islands and the Florida Keys.171,180 Other “fire sponges” have a similar appearance (Figure 80-3, online). This sponge grows in thick branches, which extend from a larger base and are easily broken off. Other culprits include Fibula (or Neofibularia) nolitangere, the poison bun sponge (Figure 80-4) (and the related sponge Neofibularia mordens), and Microciona prolifera, the red moss sponge (found in the northeastern United States).98 F. nolitangere is found in deeper water and grows in clusters, with holes (oscula) large enough to admit a diver’s finger. It is brown (Figure 80-5) and bready in texture, so it may crumble in the hands.

Within a few hours after skin contact, but sometimes within 10 to 20 minutes, the reactions appear. They are characterized by itching and burning, which may progress to local joint swelling, soft tissue edema, vesiculation, and stiffness, particularly if small pieces of broken sponge are retained in the skin near the interphalangeal or metacarpophalangeal joint. Most victims of sponge-induced dermatitis have hand involvement, because they handled the sponges without proper gloves. In addition, abraded skin, such as that which has been scraped on stony coral, may allow more rapid or greater absorption of toxins.164 When the sponge is penetrated, torn, or crumbled, the skin is exposed to the toxic substances. Untreated, mild reactions subside within 3 to 7 days. When large skin areas are involved, the victim may complain of fever, chills, malaise, dizziness, nausea, muscle cramps, and formication. Bullae induced by contact with M. prolifera may become purulent. Systemic erythema multiforme, dyshidrotic eczema, or an anaphylactoid reaction may develop 1 to 2 weeks after a severe exposure.226 The skin may become mottled or purpuric, occasionally after a delay of up to 10 days.180

The second syndrome is an irritant dermatitis and follows penetration of small spicules of silica or calcium carbonate into the skin. Most sponges have spicules; toxic sponges may possess crinotoxins that enter microtraumatic lesions caused by the spicules.

In severe cases, surface desquamation of the skin may follow in 10 days to 2 months. No medical intervention can retard this process. Recurrent eczema and persistent arthralgias are rare complications.


Because distinguishing clinically between the allergic and spicule-induced reactions is usually impossible, it is reasonable to treat for both. The skin should be gently dried. Spicules should be removed, if possible, using adhesive tape, a thin layer of rubber cement, or a facial peel. As soon as possible, dilute (5%) acetic acid (vinegar) soaks for 10 to 30 minutes 3 or 4 times a day should be applied to all affected areas.180,184,225 Isopropyl alcohol (40% to 70%) is a reasonable second choice. Although topical steroid preparations may help relieve the secondary inflammation, they are of no value as an initial decontaminant. If they precede the vinegar soak, they may worsen the primary reaction. Delayed primary therapy or inadequate decontamination can result in the persistence of bullae, which may become purulent and require months to heal.

Erythema multiforme or dyshidrotic eczema may require administration of a systemic glucocorticoid, beginning with a moderately high dose (prednisone, 60 to 100 mg) tapered over 2 to 3 weeks. Anecdotal remedies for the management of sponge envenomation that have been suggested without demonstration of efficacy include antiseptic dressings, broad-spectrum antibiotics, methdilazine, tripelennamine, phenobarbital, diphenhydramine, promethazine, and topical carbolic oil or zinc oxide cream.180

After the initial decontamination, a mild emollient cream or steroid preparation may be applied to the skin. If the allergic component is severe, particularly if there is weeping, crusting, and vesiculation, a systemic glucocorticoid (prednisone, 60 to 100 mg, tapered over 2 weeks) may be beneficial, as might a potent topical steroid preparation. Severe itching may be controlled with an antihistamine.

Because Clostridium tetani has been cultured from sea sponges, sponges should not be used to pack wounds. Proper antitetanus immunization should be part of sponge dermatitis therapy. Frequent follow-up wound checks are important because significant infections sometimes develop.99 Infected wounds should be cultured and managed with antibiotics (see Chapter 79). If sponge poisoning induces an anaphylactoid reaction, standard resuscitation using epinephrine, bronchodilators, corticosteroids, and antihistamines should be undertaken.226

As mentioned previously, sponge diver’s disease is not caused by any toxin produced by the sponge but rather is a stinging syndrome related to contact with the tentacles of the small coelenterate anemone Sagartia rosea (family Sagartiidae) or anemones from the genus Actinia (family Actiniidae) that attach to the base of the sponge. Treatment should include that for coelenterate envenomation (see below).

Phylum Cnidaria

The phylum Cnidaria (previously called “coelenterates” [hollow gut]) comprises an enormous group of approximately 10,000 species, at least 100 of which are dangerous to humans. The term “Coelenterata” is no longer in scientific use. It formerly encompassed the phyla Cnidaria (certain coral animals, true jellyfish [jellies], sea anemones, and sea pens) and Ctenophora (comb jellies).

Only members of the phylum Cnidaria (sometimes referred to as “cnidarians”) produce the capsule commonly called a cnida (also called cnidocyst).51 The word “cnida” is derived from the Greek word image, which means “nettle.” For practical purposes the cnidarians can be divided into four main groups: (1) hydrozoans, including hydroids, fire corals, and creatures such as the Portuguese man-of-war; (2) scyphozoans, such as true jellyfish; (3) anthozoans, such as soft corals (alcyonarians), stony corals, sea pens and anemones; and (4) cubozoans, such as box jellies. Gorgonians (order Gorgonacea, class Anthozoa, subclass Alcyonaria) secrete mucinous exudates having toxic effects in experimental animals that can be characterized as hemolytic, proteolytic, cholinergic, histaminergic, serotonergic, and adrenergic.66 Fenner divides jellyfish into three main classes: scyphozoans (true jellyfish), with tentacles arising at regular intervals around the bell; cubozoans (e.g., box-jellyfish), with tentacles arising only from the corners (and these may be further divided into carybdeids [e.g., Irukandji], with only one tentacle [except in rare cases] arising from each lower corner of the bell, and chirodropids, which have more than one tentacle in each corner of the bell); and other jellyfish, such as members of the hydrozoans (e.g., Physalia species).

Morphology, Venom, and Venom Apparatus

Cnidarians are carnivorous predators that feed on other fish, crustaceans, and mollusks. They are radially symmetric animals of simple structure (95% water) and exist in two predominant life forms—either sedentary, asexual polyps (hydroids) or free-swimming and sexual medusae. They are the lowest form of life organized into different layers.164 Generally, the polyps are sac-like creatures attached to the substrate at the caudal (aboral) end, with a single orifice or mouth at the upper end surrounded by stinging tentacles (dactylozooids). This form predominates in the hydrozoans and anthozoans. The medusa is a bell-shaped creature, with a floating gelatinous umbrella from which hang an elongated tubular mouth and marginal nematocyst-bearing tentacles. This form predominates in the scyphozoans and is also found in the hydrozoans.

Cnidocytes (include nematocytes, spirocytes, and ptychocytes) are mature living cells that encapsulate the nonliving intracytoplasmic capsules called cnidae (or cnidocysts: include nematocysts, spirocysts, and ptychocysts), within which are found the stinging apparatus. Cnidae are secreted by the Golgi apparatus of cells (cnidoblasts: include nematoblasts, spiroblasts, and pychoblasts) specialized for this function. Nematocysts are initially found in differentiating clusters. After differentiation into the different types of capsules, the clusters break up to allow single nematocytes to migrate to tentacles, where they become mounted in specialized tentacle epithelial cells, called battery cells.191 The nematocytes are located on the outer epithelial surfaces of the tentacles (Figure 80-6) or near the mouth and are triggered by contact with the victim’s body surface. The nematocyst is contained within the cnidoblast, to which is attached a single pointed “trigger,” or cnidocil. The undischarged nematocyst (3 to 100 µm in diameter) varies in shape and is under high osmotic pressure created during capsule morphogenesis by synthesis of poly-γ-glutamate in the capsule matrix. Minicollagen networks determine the structure of the nematocyst wall.43 The nematocyst contains a hollow, sharply pointed, coiled, or folded “thread” tubule (nema) (Figure 80-7). This tubule may attain lengths of 200 to 850 µm and is sufficiently hardy to penetrate a surgical glove. The tubule is initially formed outside the capsule and then invaginates within the wall, so that in the undischarged state, the toxin is located in the folds and invaginations of the tubule’s membrane. This membrane hardens via disulfide bond isomerization to form bridges between minicollagen peptides as the capsule attains its final size.191

The tubule is lined with hollow barbs, which help it penetrate and anchor into the victim. In the undischarged state, the barbs occupy the lumen of the twisted and folded tubule. When the cnidocil is stimulated, either by physical contact or by a chemoreceptor mechanism, it causes the opening of a trapdoor (operculum) in the cnidoblast, and the venom-bearing tubule is everted (Figure 80-8) within 3 µsec. This exocytosis has been hypothesized to occur because of osmotic swelling of the capsular matrix caused by high concentration of poly-γ-glutamate, influx of water (leading to a hydrostatic pressure of up to 150 atm), release of intrinsic tensile forces (up to 375 MPa on the inner capsule wall), or deformation of the wall-induced internal pressure.86,87,191 The sharp tip of the thread tube enters the victim’s skin (Figures 80-9 and 80-10), and envenomation occurs as toxin is translocated by hydrostatic forces from the surface of the everted and extended tubule through the now helically arranged (Figure 80-11) and extended hollow barbs.113,114 It has been estimated that the velocity of ejection attains 2 m/sec, which corresponds to an acceleration of 40,000g, with an estimated skin striking force of 2 to 5 psi.49 This is one of the most rapid mechanical events found in nature. A human encounter with a large Portuguese man-of-war could conceivably trigger the release of several million stinging cells (Figure 80-12). It has been estimated that more than 2000 sting penetrations can occur within a single square millimeter of skin. The threads penetrate the epidermis and upper dermis, where the venom diffuses into the general circulation. The agitated victim moves about and assists the venom’s distribution by the muscle-pump mechanism. On the basis of mouse studies, it appears that the rapid death of a victim is related to the venom that is discharged directly into capillaries, as opposed to that which must diffuse from the dermis into the bloodstream.

In the case of the Indo-Pacific box-jellyfish C. fleckeri, which may carry up to 59 tentacles bearing millions of nematocysts, it is the cigar-shaped microbasic p-mastigophores that are most important in human envenomation (Figure 80-13). The capsule of the structure holds a hollow coiled tube and granular matrix. The thread tube has a thick butt end that is attached to the operculum. The tube contains three rows of helically arranged spines. When the nematocyst fires into the human victim, the tube everts through the opercular end of the nematocyst, with the butt anchoring first to keep the nematocyst adherent to the victim. The thread then everts through the hollow butt and uncoils, presenting the spines and accompanying toxins to the living tissue. Although the major toxic fractions appear to be present in the nematocysts, there appears to be toxic material present in tentacles denuded of such organelles.21 The largest nematocysts of C. fleckeri can penetrate human skin to a depth of 0.9 mm.130

Cnidarian venoms are viscous mixtures of proteins, carbohydrates, and other nonproteinaceous components. Although they are heat labile in vitro, this does not seem to apply in the clinical setting. To date, they have been difficult to fractionate. The primary difficulties encountered in jellyfish venom purification have been the lack of stability and the tendency of active toxins to adhere to each other and to support matrices.147 Lyophilized crude venom can be prepared in water by homogenization, sonication, and rapid freeze-thawing. A second technique consists of grinding samples with a glass mortar and pestle and using phosphate-buffered saline. This has been done to prepare crude venom from isolated nematocysts of the box-jellyfish, the bells of Irukandji jellyfish, and the oral lobes of blubber jellyfish.216 Analyses of Western blot tests showed that box-jellyfish antivenom reacted specifically with the venom of each jellyfish, but there is not yet any clinical significance to this observation. Because toxicity was found in the Irukandji jellyfish venom derived by the mortar-and-pestle method, but not by the lyophilization method, the former was deemed the more efficacious method. Within box-jellyfish venom are protein components ranging from 18 to more than 106 kDa.

Cytolytic toxins have been characterized from Physalia physalis, Rhizostoma pulmo (Figure 80-14), C. fleckeri, and Carybdea marsupialis. Hemolytic activity, phospholipase A2, and α-chymotrypsin–like serine protease activity have been noted in the venom of Rhopilema nomadica.75 Many jellyfish and marine animal venoms generate autonomic neurotoxicity.34 This may be a result of their ability to affect ion transport (sodium and calcium in particular), induce channels or pores in nerve and muscle cell membranes, alter membrane configurations, and release mediators of inflammation. Cnidarian venoms can target the myocardium, Purkinje fibers, atrioventricular (AV) node, and aortic ring, as well as injure the hepatic P-450 enzyme family.

Freshwater jellyfish, such as the Appalachian mountain jellyfish Craspedacusta sowerbyi, do not appear to pose a hazard to humans.

Clinical Aspects

For clinical purposes, a considerable phylogenetic relationship exists among all stinging species, so that the clinical features of the coelenterate syndrome are fairly constant, with a spectrum of severity. The severity is related to the season and species (venom potency and configuration of the nematocyst), the number of nematocysts triggered and the size of the animal (venom inoculum), the size and age of the victim (the very young and old and the smaller person tend to be more severely affected), the location and surface area of the sting, and the health of the victim. The wise clinician suspects a coelenterate envenomation in all unexplained cases of collapse in the surf, diving accidents, and near-drownings. Any victim in distress pulled from marine waters should be carefully examined for one or more cutaneous lesions that may provide the clue to a coelenterate envenomation.

Mild envenomation may result in only an annoying dermatitis, whereas severe envenomation can progress rapidly to involve virtually every organ system, resulting in significant morbidity and mortality. Clinical envenomation is described here by severity, with the understanding that there is a fair amount of overlap. In the following paragraphs, syndromes associated with specific classes of creatures are discussed in greater detail.

Mild Envenomation

The stings caused by the hydroids and hydroid corals, along with lesser envenomations by Physalia, Velella velella (Figure 80-15), Drymonema dalmatinum (stinging cauliflower), Olindias sambaquiensis (Figure 80-16, online) (known as relojinho in Portuguese; endemic to the Blanca Bay area south of Buenos Aires province and found on the southeastern Brazilian coast) (Figure 80-17), scyphozoans, and anemones, result predominantly in skin irritation.77,100 Nemopilema nomurai (“echizen kurage”) is a large stinging jellyfish, with a maximum bell size of 2 m and weight of 200 kg, that blooms in the orient.92 There is usually an immediate pricking or stinging sensation, accompanied by pruritus, paresthesias, burning, throbbing, and radiation of the pain centrally from the extremities to the groin, abdomen, and axillae. The area involved by the nematocysts becomes red–brown–purple, often in a linear whiplike fashion, corresponding to tentacle prints (Figures 80-18 and 80-19, online). Other features are blistering, local edema, angioedema, and wheal formation (Figures 80-20 and 80-21, online), as well as violaceous petechial hemorrhages. Dyspnea due to upper airway obstruction associated with severe facial swelling is possible.5 The papular inflammatory skin rash is strictly confined to the areas of contact and may persist for up to 10 days. Areas of body hair appear to be somewhat more protected from contact than are hairless areas. If the envenomation is slightly more severe, the aforementioned symptoms, which are evident in the first few hours, can progress over a course of days to local necrosis, skin ulceration, and secondary infection. This is particularly true of certain anemone (Sagartia, Actinia, Anemonia, Actinodendron, and Triactis) stings. A painless “jellyfish sting,” in which there is a pattern of hyperpigmented linear streaks, might represent the occurrence of phytophotodermatitis (e.g., from citrus juice spilled on skin and later exposed to light).20

Untreated, the minor to moderate skin disorder resolves over 1 to 2 weeks, with occasional residual hyperpigmentation for 1 to 2 months. Rubbing can cause lichenification. Local hyperhidrosis, fat atrophy, and contracture may occur.25 Mondor’s disease of the breast has been reported following jellyfish stings.88 Facial swelling with sterile abscess formation has been reported.192 Permanent scarring or keloids may result. Persistent papules or plaques at the sites of contact may demonstrate a predominantly mononuclear cell inflammatory infiltrate, which may represent a delayed hypersensitivity response to an antigenic component of the coelenterate nematocyst or venom. This may be accompanied by localized arthritis and joint effusion. It has been suggested that sensitization may occur without a definite history of a previous sting, because coelenterates may release antigenic and allergenic venom components into the water. Granuloma annulare, which is usually both a sporadic and a familial inflammatory dermatosis, has been associated with a Physalia utriculus envenomation.119 Gangrene has been observed.

Moderate and Severe Envenomation

The prime offenders in this group are the anemones, Physalia species, and scyphozoans. The skin manifestations are similar or intensified (as with Chironex) and are compounded by the onset of systemic symptoms, which may appear immediately or be delayed by several hours:

The extreme example of envenomation occurs with C. fleckeri, the dreaded box jellyfish. Physalia and anemone stings, although extremely painful, are rarely fatal. Death after Physalia stings has been attributed to primary respiratory failure or cardiac arrhythmia, which may have reflected an element of anaphylaxis.30,185 Confirmed deaths after coelenterate envenomation have been attributed to C. fleckeri, Chiropsalmus quadrigatus, and Chiropsalmus quadrumanus (Figure 80-22).130 Stomolophus nomurai (the sand jellyfish) has caused at least eight deaths in the South China Sea.53 Although there have been other deaths, the animals have not been definitively identified.

Clinical reports and studies on the serologic response to jellyfish envenomation suggest that allergic reactions may play a significant pathophysiologic role in humans. When crude or partially purified nematocyst venom and an antigen are used in an enzyme-linked immunosorbent assay (ELISA), both IgG and IgE can be detected.69,165 Elevated specific anti–jellyfish IgG and IgE may persist for several years, recurrence of the clinical cutaneous reaction to jellyfish stings may occur within a few weeks without additional contact with the tentacles, and serologic cross-reactivity between the sea nettle (Chrysaora quinquecirrha) and P. physalis occurs. In a case of significant envenomation by the moon jellyfish Aurelia aurita (Figure 80-23), the victim developed significant cross-reacting antibodies to C. quinquecirrha antigens.29

Persons with extracutaneous or anaphylactoid responses to a coelenterate sting have been noted to have higher specific IgG and IgE antibody levels.165 However, elevated persistent specific anti-jellyfish serum IgG concentrations are not protective against the cutaneous pain resulting from a natural sting.28 A false-positive ELISA serologic test to venom may occur, as demonstrated by negative skin testing.

A person stung by P. physalis may have recurrent cutaneous eruptions for 2 to 3 weeks after the initial episode, without repeated exposure to the animal. This may take the forms of lichenification, hyperhidrosis, angioedema, vesicles, large bullae, nodules that resemble erythema nodosum, granuloma annulare, or a more classic linear urticarial eruption.8,27,120 Recurrent eruptions have also followed a solitary envenomation by the cnidarian Stomolophus meleagris.24 In a histologic study of delayed reaction to a Mediterranean Sea coelenterate, skin biopsy demonstrated grouping of human leukocyte antigen–DR-positive cells with Langerhans cells and helper/inducer T lymphocytes, which indicates the possibility of a type IV immunoreaction.153

Venom-specific IgG antibodies appear to persist for longer periods than IgM antibodies. The binding of brown recluse spider venom and purified cholera toxin to anti-Chrysaora and anti-Physalia monoclonal antibodies indicates that there may be a common or cross-reacting antigenic site or sites between these toxic substances and certain coelenterate venoms.145

Acute regional vascular insufficiency of the upper extremity has been reported after jellyfish envenomation. It can be manifested by acral ischemia, signs and symptoms of compartment syndrome, and massive edema.211


Therapy is directed at stabilizing major systemic decompensation, opposing the venom’s multiple effects, and alleviating pain.

Systemic Envenomation

Generally, only severe Physalia or Cubomedusae stings result in rapid decompensation. In both cases, supportive care is based on the signs and symptoms. Hypotension should be managed with the prompt IV administration of crystalloid, such as lactated Ringer’s solution. This must be done in concert with detoxification of any nematocysts (particularly those of Chironex or Chiropsalmus) that are still attached to the victim, to limit the perpetuation of envenomation. Hypotension is usually limited to very young or older adult victims who suffer severe and multiple stings, the effects of which are worsened by the fluid depletion that accompanies protracted vomiting. Hypertension is an occasional side effect of a cubomedusan envenomation, such as that of the Irukandji Carukia barnesii. Excessive catecholamine stimulation is one putative cause, which has prompted clinical intervention with benzodiazepines, magnesium, and phentolamine, an α-adrenergic blocking agent (5 mg IV as an initial dose, followed by an infusion of up to 10 mg/hr). Bronchospasm may be managed as an allergic component. If the victim is in respiratory distress with wheezing, shortness of breath, or heart failure, supplemental oxygen administration will be necessary by face mask or a continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) circuit. Arterial blood gas measurement may be used to guide oxygen therapy. Seizures are generally self-limited but should be managed with IV diazepam for 24 to 48 hours, after which time they rarely recur.

Any victim with a systemic component should be observed for a period of at least 6 to 8 hours, because rebound phenomena after successful treatment are not uncommon. All older adult victims should undergo electrocardiography and be observed on a cardiac monitor, with frequent checks for arrhythmias. Urinalysis demonstrates the presence or absence of hemoglobinuria, indicating hemolysis after the putative attachment of Physalia venom to red blood cell membrane glycoprotein sites.74 If this is the case, the victim’s urine should be alkalinized with bicarbonate to prevent the precipitation of pigment in the renal tubules, while a moderate diuresis (30 to 50 mL/hr) is maintained with a loop diuretic (such as furosemide or bumetanide) or mannitol (0.25 g/kg IV every 8 to 12 hours). In rare instances of acute progressive renal failure, peritoneal dialysis or hemodialysis may be necessary.

If there are signs of distal ischemia or an impending compartment syndrome, standard diagnostic and therapeutic measures apply. These include Doppler ultrasound, angiography, or both for diagnosis, regional thrombolysis for acutely occluded blood vessels, measurement of intracompartmental tissue pressures to guide fasciotomy, and so forth. Reversible regional sympathetic blockade may be efficacious if vasospasm is a dominant clinical feature. However, vasospasm associated with a jellyfish envenomation may be severe, prolonged, and refractory to regional sympathectomy and intraarterial reserpine or pentoxifylline.1

A small child may pick up tentacle fragments on the beach and place them into his or her mouth, resulting in rapid intraoral swelling and potential airway obstruction, particularly in the presence of exceptional hypersensitivity. In such cases, an endotracheal tube should be placed before edema precludes visualization of the vocal cords. In no case should any liquid be placed in the mouth if the airway is not protected. In 1999, a lifeguard in Cairns, Australia, drank from a container containing 4-day-old C. fleckeri tentacles. He fortunately suffered only a sore throat and transient shortness of breath.

C. fleckeri, the box-jellyfish, produces the only coelenterate venom for which a specific antidote exists (see below). To date, the venoms of Physalia and Chrysaora species have not been sufficiently purified as antigens to permit the production of an antitoxin. Antivenom administration should accompany the first-aid protocol previously described.

Treatment of Dermatitis

If a person is stung by a coelenterate, the following steps should be taken:

Commercial (chemical) cold or ice packs applied over a thin dry cloth or plastic membrane have been shown to be effective when applied to mild or moderate Physalia utriculus (or bluebottle [see below]) stings.49 Whether the melted-water from ice applied directly to the skin can stimulate the discharge of nematocysts has not been determined. It has been observed by physicians in Australia that hot packs and hot showers (45° C [113° F]) are efficacious for relieving the pain of bluebottle stings. Heat therapy may be as effective as applying vinegar or another decontaminant (see below).

For a sting from C. fleckeri, if vinegar is immediately available, a liberal dousing should occur and at least 30 seconds should pass before removing the tentacles. It is not recommended to use the pressure-immobilization technique for venom containment. A venolymphatic proximal (to the injury) occlusive tourniquet should be considered only if a topical detoxicant is unavailable, the victim suffers from a severe systemic reaction, and transport to definitive care is delayed.

For stings from other species, there are substances that may be more specific and therefore more effective. Alternatively, nonspecific substances may be effective. Depending on the species, the most popular remedies include lidocaine (4% to 15%), isopropyl alcohol (40% to 70%), dilute ammonium hydroxide, sodium bicarbonate (particularly for stings of the sea nettle C. quinquecirrha), olive oil, sugar, urine, and papain (papaya latex [juice] or unseasoned meat tenderizer [powdered or in solution]). The last is supposed to work by cleaving active polypeptides into nontoxic amino acids. Lime or lemon juice has been observed on occasion to be effective. Ammonia has been noted to be relatively ineffective for stings of Carybdea marsupialis in the Adriatic Sea.150

Perfume, aftershave lotion, and high-proof liquor are not particularly efficacious and may be detrimental. Other substances mentioned to be effective at one time or another, but that are to be condemned on the basis of inefficacy and toxicity, are organic solvents such as formalin, ether, and gasoline.

There is some evidence that alcohol may stimulate the discharge of nematocysts in vitro; the clinical significance is as yet undetermined. The rescuer must remember that pain relief may not equate with nematocyst inhibition.130 It is worth commenting on the perpetual discussions around the efficacy of topical decontaminants. It has been observed that certain substances, such as isopropyl alcohol, that have been used to diminish the pain of a jellyfish sting, when tested in vitro (e.g., with tentacle preparations) may cause the nematocysts that reside on the tentacles of a jellyfish to discharge their contents. These observations have provoked some persons to advise against the use of the substances as remedies for jellyfish stings, sometimes stating that it would be dangerous to use them. However, what is observed under the microscope does not always match up with the observed beneficial clinical effect. It is possible that these “discharged” nematocysts are actually dead or paralyzed nematocysts that somehow lost the integrity of the capsules that contain their contents, or that they are being witnessed in an agonal and nonfunctioning state. Clearly, more research needs to be done to determine which decontaminants are clinically beneficial, which are detrimental, and the meaning of the various morphologies and activities of nematocysts under different conditions, including exposure to topical first aid remedies.

A commercial aqueous solution of aluminum sulfate (20%) and 1.1% anionic surfactant in aqueous solution (Stingose) has been mentioned in the past as effective on the basis that the aluminum ion interacts with proteins and long-chain polysaccharide components to denature and inactivate venom. Prior treatment with topical alcohol or methylated spirits reduces the effectiveness of the aluminum sulfate solution. This product has essentially fallen out of favor with clinician jellyfish experts in Australia.

4 Immersing the area in hot water is increasingly recommended, despite the premise that a hypotonic solution is felt to cause nematocysts to discharge. One study compared hot (40° to 41° C [104° to 105.8° F]) water immersion to papain meat tenderizer or vinegar for treatment of a single-tentacle Carybdea alata (Hawaiian box) jellyfish sting to the forearm, and the hot water immersion was found to be the most efficacious.141 In a crayfish model of envenomation, exposure to heat reduced the lethality of extracted C. fleckeri venom.36 At temperatures of 43° C (109.4° F) and greater, venom lost its lethality more rapidly the longer the exposure time. Because of the speed of onset of symptoms after C. fleckeri envenomation, this approach may be of limited clinical usefulness, and until human clinical confirmation against other species is obtained, hot water application should not automatically be extrapolated to other species.

Persistent Cutaneous Hypersensitivity

Persistent local dermal hypersensitivity may occur after a jellyfish sting, such as that from the Hawaiian box-jellyfish C. alata.194 This is characterized by erythematous papulonodular lesions in the pattern of the original sting, which may persist for months. Treatment, which may be unsatisfactory, consists of topical and intralesional steroids.


A topical jellyfish sting inhibitor has been commercialized. Safe Sea (“jellyfish-safe sunblock”) by Nidaria Technology, Ltd, Zemah, Jordan Valley, Israel (http://www.nidaria.com) was compared in a blinded fashion with conventional sunscreen for protection against Chrysaora fuscescens (sea nettle) and Chiropsalmus quadrumanus jellyfish. Subjects were stung with jellyfish tentacles on each forearm for up to 60 seconds, and erythema and pain were assessed at 15-minute intervals over a 2-hour period. The jellyfish sting inhibitor prevented sting symptoms of C. fuscescens in 10 of 12 subjects and diminished the pain of the jellyfish sting in the remaining two subjects.97 It was equally impressive with C. quadrumanus. The inhibitor is formulated to inactivate jellyfish stinging in several ways: (1) it is hydrophobic and thus prevents tentacles from making sufficient skin contact to induce a sting; (2) glycosaminoglycans in the inhibitor mimic the same compounds found in the jellyfish bell, thus causing self-recognition; (3) the inhibitor contains a competitive antagonist to nonselective receptors on the jellyfish that bind to amino acids and sugar secretions from prey; and (4) calcium and magnesium within the inhibitor block transmembrane signaling channels of the jellyfish, thereby altering the osmotic forces required to generate the firing pressure within the nematocyst capsule.97 The product has not yet been tested prospectively against Physalia, Carukia, or Chironex species, to name a few.

Derma Shield is a topical formulation that contains lanolin, aloe vera, and vitamin E. According to the manufacturer, this chemically inert (1-vinyl-2-pyrrolidione) barrier protectant is hydrophobic (dimethicone and stearic acid) and does not wash off but is shed as the epithelium sloughs naturally. It has been reported anecdotally by ocean bathers to protect against the agents of seabather’s eruption. To this author’s knowledge, no prospective evaluation of the use of Derma Shield to protect against any coelenterate has been published.

Smerbeck and co-workers were assigned a U.S. patent in 1999 for a method and composition of polymeric quaternary ammonium salts for protecting the skin from jellyfish stings.

A protocol has been developed to establish the effectiveness of topical agents to block firing of nematocysts.33 Unreliable topical barriers include petrolatum, mineral oil, silicone ointment, cocoa butter, and mechanic’s grease.

If jellyfish are sighted, they should be given a wide berth because the tentacles may trail great distances from the body. All swimmers and divers in hazardous areas should be on constant alert. Persons should not dive headfirst into jellyfish-infested waters; it is far safer to walk in. Bathers should wear protective clothing in infested areas. This includes Lycra “stinger suits” or a double thickness of panty hose. In hot weather, it is possible to cause human heat storage while stinger suits are being worn during beach activities, so one should be cognizant of the potential for heat-related illness when out of the water.181 If “stinger enclosures” are present, bathers should stay within the netted barriers, although it should be noted that the small (2 cm) Irukandji jellyfish will pass with ease through the mesh of a stinger net. Many bathers suffering from Irukandji envenomations in northern Queensland, Australia were swimming in a “stinger enclosure” at the time of their envenomation.

Divers concerned about jellyfish tentacles dangling from the surface or congregations of creatures at the surface should remain deeper than 20 feet and should always check snorkel and regulator mouthpieces for tentacle fragments before entering the water in endemic areas. In areas inhabited by anemones and hydroid corals, protective gloves should be worn when handling specimens. Beached dead jellyfish or tentacle fragments washed up after a storm can still inflict serious stings. Any person stung by a jellyfish should leave or be assisted from the water because of the risk of drowning.

The Consortium of Jellyfish Stings publishes a newsletter (http://medschool.umaryland.edu/dermatology/jellyfish.asp).

Class Hydrozoa

The hydrozoans range in configuration from the feather hydroids and sedentary Millepora hydroid coral to the free-floating siphonophore Physalia (Portuguese man-of-war).


Hydroids are the most numerous of the hydrozoans. The feather hydroids of the order Leptomedusae, typified by Lytocarpus philippinus (fire weed or fire fern), are feather-like or plumelike (Figure 80-24) animals that sting the victim who brushes against or handles them.160 After a storm, the branches may be fragmented and dispersed through the water, so that merely diving or swimming in the vicinity causes itching and may induce visible skin irritation.

Clinical Aspects

Contact with the nematocysts of a feather hydroid induces a mild reaction, which consists of instantaneous burning, itching, and urticaria. If the exposure is brief, the skin rash may not be noticeable or it may consist of a faint erythematous and miliary irritation (Figure 80-25). A second variety of envenomation consists of a delayed papular, hemorrhagic, or zosteriform reaction (Figure 80-26) with onset 4 to 12 hours after contact. Rarely, erythema multiforme or a desquamative eruption may develop. In turbulent waters or in a strong current, fragments may be washed into a diver’s mask or regulator mouthpiece; this will be evident as a burning sensation in the conjunctivae or oral mucous membranes. Systemic manifestations (such as abdominal pain, nausea, vomiting, diarrhea, muscle cramps, and fever) are rarely reported and are associated with large areas of surface involvement. Allergic sensitization and subsequent anaphylaxis have been proposed.

Fire Coral

The stony, hydroid, and coral-like Millepora species (e.g., Millepora alcicornis), or fire corals, are not true corals. They are widely distributed in shallow tropical waters. Sessile creatures, they are found attached to the bottom in depths of up to 1000 m (3281 feet). They are often mistaken for seaweed because they attach to pilings, rocks, shells, or coral. Although smaller segments resemble Christmas trees or bushes 7.6 to 10.2 cm (3 to 4 inches) in height, they may attain heights of 2 m (6.6 feet). The color ranges from white to yellow-green, with pale yellow (Figure 80-27) most common. Rare purple fire corals exist. Fire coral is structured on a razor-sharp calcium carbonate (calcic limestone) exoskeleton, which is an important component in the development of coral reefs. The outcroppings assume upright, clavate, blade-like, honeycomb, or branching calcareous growth structures that form encrustations over coral and objects such as sunken vessels. From numerous minute surface gastropores protrude tiny nematocyst-bearing tentacles, wherein lies the stinging apparatus. M. alcicornis probably accounts for more coelenterate envenomations than any other species. Unprotected and unwary recreational scuba enthusiasts handle, kneel on, or lean on this marine stinger.

Clinical Aspects

Immediately after contact with fire coral, the victim suffers burning or stinging pain, rarely with central radiation. Intense and painful pruritus follows within seconds, which frequently induces the victim to rub the affected area vigorously, worsening the envenomation. Over the course of 5 to 30 minutes, urticarial wheals develop, marked by redness, warmth, and pruritus (Figure 80-28). The wheals become moderately edematous and reach a maximal size in 30 to 60 minutes. Untreated, they flatten over 14 to 24 hours and resolve entirely over 3 to 7 days, occasionally leaving an area of hyperpigmentation (Figure 80-29) that may require 4 to 8 weeks to disappear. The pain generally resolves without treatment in 30 to 90 minutes. A hemorrhagic or ulcerative lesion(s) may occur acutely. In the case of multiple stings, regional lymph nodes may become inflamed and painful. This does not necessarily indicate a secondary infection. The skin may take on the appearance of leukocytoclastic vasculitis.148 Long thoracic mononeuritis with serratus anterior muscle paralysis has been described after Millepora sting, confirmed by demonstrated presence of immune-specific IgG.133 Delayed skin reaction after Red Sea fire coral injury was characterized by superficial granulomas and atypical CD30+ lymphocytes (Figure 80-30).132 In another series, contact with fire coral resulted in a typical pruritic urticarial lesion and blister formation, followed by a lichenoid stage that developed 3 weeks after the initial injury; resolution, with residual hyperpigmented macules, required 15 weeks.2 A persistent cutaneous reaction characterized by eczematous dermatitis lasting more than 18 months is possible.148 Grouped or linear papulonodular lesions, round or oval in shape, may follow as a delayed reaction to jellyfish sting.201 In a rare case, a full-thickness skin burn may occur.166


FIGURE 80-29 Hyperpigmentation of forearm depicted in Figure 80-22 after a fire coral sting.

(Courtesy Kenneth Kizer, MD.)

Renal minimal change disease (nephrotic syndrome, renal failure) responsive to corticosteroid therapy has been associated with fire coral exposure.155

Physalia (Man-of-War)

The Atlantic Portuguese man-of-war (Physalia physalis) of the phylum Coelenterata, order Siphonophora, is a pelagic (open sea) polymorphic colonial siphonophore that inhabits the surface of the ocean. It is constructed of a blue or pink-violet and iridescent floating sail (pneumatophore) that is filled with nitrogen and carbon monoxide and up to 30 cm (11.8 inches) in length, from which are suspended multiple nematocyst-bearing tentacles, which may measure up to 30 m (98 feet) in length (Figure 80-31). It has recently been reported that an Australian version of P. physalis is present in northern Australian waters.58 This jellyfish is characterized by float lengths of up to 15 cm (5.9 inches), up to five thick, dark blue “main” tentacles, and up to 10 other long, thin, and pale-colored tentacles. The smaller Pacific bluebottle (Physalia utriculus) usually has a single fishing tentacle, which attains lengths of up to 15 m (49.2 feet). In some species, the sail can be deflated to allow the animal to submerge in rough weather.

Only gold members can continue reading. Log In or Register to continue

Sep 7, 2016 | Posted by in EMERGENCY MEDICINE | Comments Off on Envenomation by Aquatic Invertebrates

Full access? Get Clinical Tree

Get Clinical Tree app for offline access