Physalia species are improperly believed to be “jellyfish”: They are a Siphonophore colony of animals in the class hydrozoa. Two major Physalia spp. are commonly classified within this group [1,2]: (1)

Physalia physalis (the Portuguese Man O’ War): This worldwide species has a boat-like pneumatophore 2–25 cm long, with multi-tentacles measuring from 10 m up to 30 m [1]; yet, it is not a true jellyfish. This species is responsible for a large number of stings, with some being fatal.

The pneumatophore and the predominant tentacle are usually bright bluish, although in the Atlantic specimens, they may be purplish. This float allows them to sit on the surface of the ocean and lean horizontally when the wind blows, sailing with the wind, as well as being carried by water currents [2,3,26].

Physalia spp., which are responsible for a substantial proportion of cnidarians’ stings worldwide, have a widespread distribution [37]. Both Physalia physalis and Physalia utriculus may be found in Indo-Pacific areas, the Indian Ocean and the South Atlantic [1], whereas in the North Atlantic and European coasts, only the Portuguese Man O’ War has been reported [38]. Physalia spp. are more frequently found in hot and temperate waters [2,16,26]; however, these hydrozoans can occasionally be found cast ashore in cold Atlantic waters (e.g., North France, Belgium and the South West of England). In Australia, another multi-tentacled Physalia sp. has been reported [1].

As they float on the ocean surface, often in big swarms, Physalia spp. represent a potentially significant hazard to swimmers. Physalia stranded on beaches are still capable of stinging if handled, even after several days of dehydration [1].

Physalia stings are normally quite painful and severe, with the Portuguese Man O’ War potentially also causing major systemic symptoms [1]. Physalia stings are normally multiple, always causing local symptoms with instantaneous pain: linear, crossed skin wheals longer than 20 cm with intradermal oedema in the areas having contact with the tentacles [1]. Some severe skin injuries become necrotic within 24 h, evolving into scabs lasting for about two weeks before resolving and causing enduring (if not permanent) erythematous scars [16]. The skin lesions of Physalia are quite easy to recognize, with typical spherical nematocysts detected by skin scrapings [1].

Physalia utriculus usually causes local pain only and, very rarely, minor systemic symptoms. By contrast, many patients with Physalia physalis stings suffer systemic symptoms, which generally are gastrointestinal (abdominal ache and nausea/vomiting) and/or muscular (spasms, pain). However, severe envenomations from Physalia may even produce neurological (headache, drowsiness, fainting, confusion) and cardio-respiratory syndromes (dyspnea, precordialgia). Systemic effects generally disappear rapidly with early first aid (hence, they are mostly described by the patients themselves) or may last for hours [16]. Serious envenomations have been reported from both sides of the Atlantic [39,40,41]. In 2011, about 10% of Physalia physalis victims in Aquitaine (France) presented life-threatening systemic conditions (especially respiratory distress), which required hospitalization [16]. Three fatal envenomations from Physalia have also been reported on the Southern Atlantic coasts of the United States [1,42].

Although first aid of Physalia stings is still quite controversial, the most effective treatment to alleviate pain is tentacle removal, followed by hot water application on the stung skin area. In a randomized controlled trial (RCT) conducted on 96 swimmers accidentally stung by Physalia, there was strong evidence (p < 0.002) of decreased pain at 10 and 20 min post-treatment with hot water immersion at 45 °C, as compared to ice packs [43]. These findings were somewhat confirmed by Bowra [44] in a cross-over study, which reported that victims treated with hot showers were more likely (p < 0.001) to benefit from stronger and quicker pain relief, as compared with those treated with ice packs.

Despite being conducted with a loose design (no statistical analysis and no controls employed), one study suggested ice packs as an effective remedy to alleviate pain from Physalia stings [45]. According to Exton [45], one single skin application of ice packs resolved pain in 100% of 82 victims with mild pain; a second ice pack application resolved the symptoms in 98% of another 45 patients suffering from moderate pain and in 75% of 32 patients suffering from severe pain.

Though being advocated by a few authors [7] and endorsed by laboratory evidence [46] and a RCT [47], topical vinegar is not universally accepted as treatment [1,31], as it seemingly increases nematocyst discharge from some Physalia species [1,48]. In particular, nematocyst discharge from the multi-tentacled Physalia species living in Australian waters was observed under the microscope after exposing segments of tentacles to methylated spirits (grade 5 in a scale 1 to 5) and acetic acid (grade 2) in the laboratory [49,50]. Furthermore, a recent in vitro study [51] confirmed that pieces of Physalia physalis tentacles exposed to vinegar promptly caused thousands of nematocysts to discharge. Nonetheless, there seems to be growing consensus toward vinegar use in Physalia stings, at least outside Australia, where the multi-tentacled species has not been reported thus far [1,52]. The likely mechanism of pain relief by vinegar is through blocking of additional nematocyst discharge [53].

Another effective remedy against pain from Physalia stings is Stingose (Hamilton Laboratories, Melbourne, Australia), an aqueous solution of 20% aluminum sulfate (MgSO₄) and 1.1% surfactant. In particular, topical application of Stingose and various other substances were evaluated in a RCT, where the forearms of 20 volunteers were exposed to jellyfish tentacles [47]. Although subjective criteria for pain assessment were employed, the latter study evidenced that Stingose (similar to vinegar) was significantly more effective than sea water as a painkiller. Stingose, along with other chemicals, such as baking soda slurry, papain and bromelain, were beneficial against rupture of P. physalis nematocysts in the laboratory [46]. Weak evidence in favor of papain as effective treatment for Physalia stings was proposed [54]; however, this was subsequently questioned by Burnett [55]. Similarly to vinegar, lidocaine appeared to work as an analgesic, as well as a blocker of venom discharge from tentacles adhering to the skin [51].

By contrast, application of methylated spirits was associated with increased pain sensation in the RCT conducted by Turner [47]. Exposure to ammonia, ethanol and bromelain in the laboratory also reportedly increased nematocyst discharge from suspensions of P. physalis tentacles [51]. However, in the latter study, previous lidocaine application on jellyfish tentacle stings seemed to reduce pain sensation after subsequent exposure to ammonia, bromelain, ethanol and vinegar, as a result of presumed skin numbness, rather than inhibition of nematocyst discharge.

Reserpine was found beneficial in relieving spasm of the brachial artery following a probable second contact with a Physalia sp. in one case report [56], and anti-histamine i.v. resolved a dramatic collapse with cardio-respiratory arrest and mydriasis 15 min after a sting from Physalia sp. in another case report [57].

Chironex fleckeri, named in honor of Hugo Flecker, a physician from Cairns (Queensland, Australia [60]), is responsible for several sudden and painful fatalities in Australian waters [1,2,61]. This dangerous box jellyfish can weigh up to 6 kg, with the diameter of its semitransparent cubic bell measuring about 20–30 cm. Four bundles of 10–15 translucent tentacles stem from four pedalia; the tentacles of mature specimens are generally flat and may extend up to 3 m [1].

C. fleckeri frequently moves from the open sea into shallow water to search for small prawns [1]. Therefore, shallow waters in proximity to beaches are the most frequent sites of stings [1].

C. fleckeri is considered an in-shore or coastal species, as it has never been found off-shore around coral reefs [1].

C. fleckeri is almost impossible to be seen by the victim, even after its sting [1,2]. Although the majority of stings from C. fleckeri are a minor event, with local pain and skin changes visible in the stung skin area, massive envenomation may cause severe systemic symptoms and sometimes death (usually within few minutes) [31].

Local signs of envenomation are intense skin pain with large (0.5–1.0 cm), edematous and erythematous plaques in the stung skin areas [31]. These wheals resemble whip marks. Blisters soon follow, leaving full-thickness areas of skin necrosis after the healing process (usually about 10 days). Permanent scars, which may have areas of abnormal pigmentation, are common residual patterns [1]. The severity of stings is proportional to the bell size, being extremely dangerous for C. fleckeri, with a diameter of 15 cm or more [1].

Systemic reactions to box jellyfish stings may include: dyspnea, hypotension, unconsciousness, arrhythmias and cardiopulmonary arrest [1,31]. Chironex fleckeri venom is also cardiotoxic, with a lethal component that is yet to be identified [1,62,63,64]. Experimental evidence suggests that C. fleckeri toxin can have a direct effect on the heart muscle and vascular tissue [65]. A total length of wheals of 6–7 m can cause quick loss of consciousness within seconds, with probable death even after 5–20 min or so following the envenomation [59,66]. However, severe envenomation and death is possible even with smaller skin contact [31]. Children seem to be more vulnerable to the effects of C. fleckeri venom, its lethality apparently being more likely in victims with a lower body mass [66]. Death usually occurs rapidly, as a result of cardiac asystole [2,12,31,64,66,67,68].

Presently, the appropriate first-aid management of suspected C. fleckeri stings is retrieval of the victim from the water and Basic Life Support (BLS) or Advanced Life Support (ALS), depending on the victim’s condition. Early application of vinegar (4%–6% acetic acid) for 30 s by dousing the stung skin area is the mainstay to prevent further discharge of venom from remaining nematocysts [1,31]. Adherent tentacles can be removed from the victim with the rescuer’s fingers, which will only incur relatively harmless prickling when handling them, due to the thick palmar skin (but this does not apply to other skin areas). Caution should however always be observed when handling live tentacles. It is advised not to waste time if vinegar is not available [1,2].

Laboratory studies suggest vinegar relieves pain by preventing further nematocyst discharge [53]. After vinegar application, minor stings respond well to ice pack application [64]. Opiates, such as fentanyl, are used for severe skin pain [31].

In a RCT, Stingose did not prove as effective as vinegar in inactivating nematocysts of C. fleckeri [69].

In their characterization of C. fleckeri toxin, Baxter et al. [27] showed that heat, formalin and ethylenediaminetetraacetic acid reduced all activities of the venom. The latter study hypothesized the potential of hot water immersion therapy for box jellyfish envenomation. Another experimental investigation supported the application of hot water at 43 °C or more, and C. fleckeri venom was found to lose lethality more rapidly the longer the exposure time. Lethality was assessed by time required to obtain ventricular arrest in crayfish injected with C. fleckeri tentacles treated with hot water [70]. However, the clinical application of heat on C. fleckeri venom appears to be impractical, as death after its stinging may occur within minutes [2]. Moreover, although hot water appears to be an effective treatment for pain [71], its use might be questionable, as the greatest hazard from C. fleckeri venom is a cardiotoxin [32,62]. Since the latter toxin can be carried directly and quickly into the circulatory system, applied heat may increase the blood flow, therefore resulting in increased severity of the cardiotoxic effects [72]. Carrette [70] appropriately concluded that if the sting is minor or unnoticed and systemic symptoms have already developed, heat application may be useless. In some cases, however, heat is included in the management of C. fleckeri envenomations [73]. A RCT is currently underway evaluating the effectiveness of heat in treating C. fleckeri envenomation (Seymour JE, personal communication).

In one case, the worsening clinical condition of a C. fleckeri victim following topical fresh water improved rapidly after alcohol application [12]. However, laboratory tests by Hartwick [53] reported massive nematocyst discharge following exposure of C. fleckeri tentacles to alcohol and methylated spirits.

C. fleckeri anti-venom obtained by hyper-immunizing sheep has been widely available since the 1970s and is produced by Commonwealth Serum Laboratory (Melbourne, Australia) [1,31,59,66]. Anti-venom ampoules of 20,000 units can be given intravenously over five minutes [59,66]. In order to control local symptoms (pain and local tissue damage), as well as more severe systemic effects, the anti-venom should be administered as early as possible. Although no significant adverse reactions to this antidote have been reported, there is a possibility of an allergic reaction. With consideration that the majority of victims envenomed by C. fleckeri have minimal symptoms, it is best to restrict anti-venom use to situations of cardio-respiratory instability, cardiac arrest, arrhythmias, difficulty in swallowing, severe pain resistant to opiates or significant risk of skin scarring [1,31,34]. Experiments in rats envenomed by C. fleckeri showed that a combination of the anti-venom and MgSO₄ prevented cardiovascular collapse [74].

Chiropsalmus quadrigatus is a very common species in the Indo-Pacific Ocean from Australia to the Philippines/Japan, being less frequent in the North American and Caribbean seas [2,3]. However, identification is difficult, and many different jellyfish in the Western Pacific Region are incorrectly classified as C. quadrigatus [75]. When searching for food (shrimps), this jellyfish species swims on the sea surface and can be frequently found in shallow coastal waters [1].

C. quadrigatus is smaller than C. fleckeri, the former having a bell of about 7–10 cm, with taxonomic expertise being required to distinguish C. quadrigatus from immature C. fleckeri [1]. C. quadrigatus exhibits from the four lower corners of its cubic bell one pedalium comprising 9–15 rounded tentacles about 3 m long [1].

Stings from this species cause immediate symptoms of intense pain, redness and swelling subsiding after a number of minutes, but persisting for about 24 h. Systemic symptoms (including allergic dermatitis, hypertension, bradycardia, cardiac asystole, respiratory failure with pulmonary edema, shock and thousands of deaths) have been reported along the Pacific coastal areas, but not in Australia [1,2,57,76]. C. quadrigatus envenomation is generally milder than C. fleckeri’s [47]. For this reason, it is practically impossible to distinguish C. quadrigatus from mild C. fleckeri stings, along with difficulty in distinguishing nematocysts from skin scrapings of C. fleckeri and C. quadrigatus [1]. Nematocysts of all cubozoans retrieved from skin scraping are generally difficult to identify, due to a lack of comparative characteristics [77].

Despite the various species improperly classified as C. quadrigatus, the medical approach to manage their stings does not vary across the chirodropids, as all seem to cause very similar, if not identical, symptoms [75].

As for C. fleckeri, vinegar is also used in the management of C. quadrigatus stings; analgesics, such as fentanyl or morphine, are used in more painful stings [1].

C. fleckeri anti-venom, administered to mice exposed to C. quadrigatus toxin, proved to counteract the dermoneurotic, lethal and hemolytic effects [78] and prevented the myotoxic and neurotoxic effects in vitro [79], but not the cardiovascular effects of the venom [80]. Despite the latter endorsing experimental evidence, however, clinical evidence for the use of C. fleckeri anti-venom in C. quadrigatus envenomations is still lacking [31].

Electrically stimulated Chiropsalmus sp. nematocysts underwent further discharge following pressure immobilization bandage (PIB) in vitro. This was confirmed by microscopy before and after application of 40 mm Hg PIB [81].

This species is found in warmer waters of the Atlantic Ocean from North Carolina to Brazil [82]. Its transparent cubic bell may have a diameter of up to 14 cm. Seven to nine pale mauve tentacles arise from the 4 palmate pedalia and may extend up to 3–4 m [2,3].

Contact with the tentacles of this jellyfish species can produce skin lesions, sometimes requiring medical attention [80], and can even be potentially lethal to children [2].

The beneficial effect of lidocaine was tested by Birsa et al. [51] in a two-arm non-randomized controlled trial, where two of the authors were stung on their forearms by C. quadrumanus and Chrysaora quinquecirrha. Immediate pain relief was obtained with 10% and 15% lidocaine solutions, but it took approximately one minute to achieve the same results with 4%–5% concentrations. More diluted preparations (1%–3%) required an even longer time (10–20 min). Solutions of benzocaine and ethanol were also able to elicit some benefit for skin pain, but only after 10 min. By contrast, some chemicals, such as ammonia, alcohol and vinegar, exacerbated the pain sensation.

Carukia barnesi can be found throughout all Australian waters, particularly in Queensland and Northern Territories [1,61,75]. In summer, it can inhabit shallow coastal waters, as well as the deep sea off the Greater Barrier Reef [1]. This small transparent carybdeid presents a cubic bell 2 cm wide and 2.5 cm long. Its four tentacles have a length varying from a few mm to 35 cm [2].

C. barnesi stings are usually mild or unnoticed, and the creature is hard to see. Following the sting, an oval erythematous area of 4–7 cm with a cluster of 2 mm surrounding vesicles may appear within 20 min or may not be noticed [1,2]. Thirty-sixty minutes or so after the sting, severe systemic symptoms may occur: the Irukandji syndrome—named after an Aboriginal tribe formerly populating the area north of Cairns (Queensland, Australia) [83]. This potentially deadly syndrome was proposed by Flecker in 1952, who described a pattern of characteristic symptoms following a reportedly minor sting in North Queensland [84]. However, a number of cases occurred before the responsible creature was captured in 1961 and named by Southcott, combining the words “carybdeids” and “Irukandji” to create the term “Carukia” and “barnesi”, commemorating Dr. Barnes [60,83,85]. Irukandji syndrome can consist of severe low back pain, muscle cramps in all four limbs, abdominal and chest pain, tremors, sweating, anxiety, restlessness, nausea, vomiting, headache and palpitations [1,83,85,86,87]. Since its original description, life-threatening hypertension (up to 300/150 mm Hg) [75], tachycardia, pulmonary edema and toxic global heart dilatation requiring intensive care unit (ICU) admission have been added as further complications of this syndrome [62,83,86]. Depending on the species responsible, many patients with Irukandji syndrome have pain without hypertension, while others have severe hypertension, even with effective pain control [88]. Deaths from Irukandji syndrome have been reported, due to intracerebral hemorrhage secondary to severe hypertension caused by the envenomation [89]. Although some authors suggest that cardiac dysfunction could be attributed to a myotoxin [34], according to others, it is only caused by the release of vast amounts of noradrenaline [90]. In particular, it has been suggested that the Irukandji syndrome is caused by venom disruption of the sodium ions, generating massive catecholamine release [90]. The Irukandji syndrome can be associated with the occurrence of a calcitonin gene-related peptide [91], endogenous catecholamines and stress cardiomyopathy [92,93]. Raised troponin levels have been reported [94,95].

The syndrome, initially described in Australia, certainly exists also in other areas, such as Thailand [96], French West Indies [97] and Florida [13], but it is probably underestimated and not medically reported.

As most Irukandji syndromes are severe, it is advisable to transport the victim to hospital in any case. The recommended first aid for pain relief in C. barnesi stings is ice packs or hot water, and prevention of further nematocyst discharge is application of vinegar [2,98], though no conclusive evidence in favor of vinegar exists [83,99]. In case of Accident and Emergency (A and E) admission, the mainstays are parenteral opiate analgesia [94], antihypertensive medication (5 mg phentolamine i.v. [88]) and 10% calcium gluconate i.v. for muscle spasms [100]. In 10 cases of Irukandji syndrome, victims required high dosages of opiates to relieve pain and seemed to benefit from magnesium sulfate (MgSO₄) i.v., which also resolved the hypertension [100]. Although magnesium is known to work effectively as an antihypertensive by reducing vascular resistance, its analgesic properties still remain unexplained [83]. Sublingual glyceryl trinitrate has also been used as a first aid pre-hospital treatment for Irukandji syndrome to transiently lower blood pressure [88], but no evidence exists for instituting such therapy to relieve patient pain or improve the victim’s ultimate outcome (pulmonary oedema or myocardial insult). Severe cases may require ALS with intubation and inotropic pharmacological support (dopamine and adrenaline), usually due to cardiac failure [83]. There is no evidence that C. fleckeri anti-venom is effective to treat the Irukandji syndrome, and no other antidote currently exists [1,31]. Although pain and hypertension can be managed with common medications, there is an urgent need for an antidote to contrast the cardiac effects induced by the jellyfish toxin [83].

Among 116 patients admitted to A&E departments for Irukandji syndrome in one study, C. barnesi nematocysts were found in 39 of the 40 victims undergoing skin scrapings, while the remaining case had nematocysts of uncertain identity [94]. However, in a retrospective/prospective case series of 87 people observed from 1997 to 2007 at health services in Northern Australia for symptoms consistent with Irukandji syndrome, nematocysts of variable morphology were reported from the skin scrapings of 7 patients, suggesting different species as putative agents [95].

Other carybdeid species have been recently identified in Northern and Western Australian waters as associated with cases of Irukandji syndrome [83,101]. Carybdea xaymacana, Carukia shinju, Malo maxima, Alatina mordens, Malo kingi and Morbakka fenneri (a large carybdeid resembling the Western Atlantic jellyfish Tamoya haplonema) seemingly produce a severe syndrome similar to Carukia barnesi; another species, named Gerongia rifkinae (first described in 2005), seems to cause milder health effects [83]. The Australian multi-tentacled Physalia sp. seems also to be implicated with an Irukandji-like syndrome consisting of back pain, dyspnea and anxiety [2,50,83].

This small four tentacles carybdeid is very common in all Australian waters, as well as the Western Pacific. The bell is 3 cm wide and 5 cm long, with tentacles ranging from 5 up to 30 cm [1].

Stings normally produce four wheal marks 3–12 mm wide, with delayed and moderate pain (for 2 h), swelling and erythema (generally for 2–3 days). Pigmentary changes may persist for two weeks after the sting [1]. Stings from this carybdeid species do not cause the Irukandji syndrome [83].

First aid for C. rastoni stings relies on the same measures as for C. fleckeri [1]. There is laboratory evidence that vinegar inhibits the firing of nematocysts [99], whereas alcohol and methylated spirits should be avoided, as they cause massive discharge. Other substances found to inactivate nematocysts are Stingose and baking soda slurry [99]; however, the latter are less available and more expensive than vinegar. Ice packs and local analgesic ointments may be effective painkillers in more severe cases [2].

Carybdea alata (also known as Alatina moseri [83]) is a tropical carybdeid species very common in Hawaiian and Eastern Pacific waters [2,87]. The bell, twice higher than wide, has a diameter measuring up to 230 mm and presents a blunt flat head. The four tentacles are generally longer than the umbrella diameter. The bell is normally milky white, and the tentacles are pink [2].

Stings from C. alata are generally not lethal. Pain is normally moderate to severe and lasts about 2 h; typical skin marks are four wheals of about 10–20 cm in length and 3–12 mm in width; subsequent vesicles and pigmentary changes may persist for up to two weeks after the sting [1]. Cases of anaphylaxis or anaphylactoid syndrome have been described [87]. C. alata is included among the species other than C. barnesi potentially able to cause the Irukandji syndrome [83,87].

The evidence-based first aid for pain treatment of C. alata stings in Hawaiian and Eastern-Central Pacific regions is hot water immersion [87,102].

In a paired RCT, 25 volunteers stung on both arms with C. alata tentacles were either treated with 40–41 °C hot water immersion on one limb and vinegar or papain on the other. Pain sensation at 4–20 min, assessed by visual analog scale (VAS), was significantly lower in the limbs treated with hot water. Nonetheless, assessing pain level from two simultaneous stings could be a possible element of confusion for the volunteers; moreover, control chemicals were previously described as potentially stimulating nematocyst release [102].

The analgesic properties of hot water were also assessed on 133 swimmers accidentally stung by C. alata in Hawaii [23]. Although this study suffered from a lack of randomization, blinding, intention to treat analysis and some other methodology issues, the odds ratio for pain cessation was 5.2 (95% confidence interval: 1.3–22.8) after 5–10 min following application of hot water, as compared to placebo [23,52].

Hot water immersion at 45 °C also proved to be the only treatment able to relieve skin pain on the forearms of five volunteers deliberately stung with Carybdea spp. tentacles (two stings per arm). Although hot water provided effective pain relief at 4–10 min post-application, vinegar, ice and aluminum provided unsatisfactory (i.e., incomplete and/or temporary) benefits [103].

In another retrospective quantitative analysis of medical records from 113 jellyfish victims in Hawaii, hot showers were more likely to relieve pain than parenteral analgesics or tranquilizers, particularly in the case of Irukandji-like syndrome [87].

In a follow-up study of 62 swimmers accidentally stung by C. alata in Hawaii, Thomas [104] observed no significant difference at VAS pain serial measurements in victims treated with papain (N = 14), freshwater (N = 19), seawater (N = 16) and aerosolized Stingose (N = 13). However, randomization was not feasible in this study, loss of follow up at 10 min was substantial and responsible jellyfish species were not properly identified [54].

This large carybdeid found in Queensland is similar to Tamoya sp. [2]. It has a transparent bell normally 10 cm high and 6 cm large [84]. Contact with its tentacles causes an immediate burning pain lasting approximately 24 h, with wheals 20 mm wide [2].

A number of substances have been tested in laboratory by Fenner et al. [105] on Morbakka tentacles with sea water as control. Vinegar fully inhibited nematocyst discharge, whereas methylated spirits caused 100% rupture. Other chemicals, such as Stingose, baking soda slurry and sodium hypochlorite, did not cause discharge from the tentacles determined by microscopic examination; however, if the same treated tentacles were subsequently applied onto the forearm, skin itching and erythema occurred [105].

Pelagia noctiluca is an ubiquitous species, being distributed in tropical, as well as Northern Atlantic and Pacific oceans [1]. It is reportedly very common in the Mediterranean Sea [25,107].

This medusa has a hemispherical bell whose diameter usually measures about 12 cm and presents numerous stinging wart-like protuberances. The bell can be transparent to fluorescent light pink, colored by violet warts. Sixteen marginal 30–40 cm long tentacles stick out from the umbrella, with mouth arms about five-times the bell height. The tentacles and the mouth arms are normally colorless or red/magenta [2,3].

Pelagia noctiluca is a severe stinging jellyfish causing local symptoms, such as pain, erythema, edema and vesicles. This jellyfish is able to restore its stinging capacity after only a few days following nematocyst liberation [25]. Although very painful, P. noctiluca stings are usually not considered life-threatening, as systemic symptoms are relatively uncommon [1,25]. Cases of anaphylaxis post-envenomation with P. noctiluca have been reported in the literature [108].

Sea water and ice packs appear to be the most appropriate management of stings from this species, whereas vinegar should be avoided, as it triggers nematocyst discharge [1,98,106,109].

Discharge of P. noctiluca nematocysts was stimulated in laboratory by anionic solutions, such as Cl⁻ and especially I⁻, whereas venom release was blocked by cations, such as Mg²⁺, as well as Ba²⁺ and, above all, Ca²⁺, which were also capable of contrasting the effect of iodide solutions on venom discharge [110].

Also called the “sea nettle”, this species is widely distributed in the Atlantic, Indian and Pacific Oceans [1]. C. quinquecirrha has a bell diameter of about 6 cm, sometimes up to 25 cm; the exumbrella is smooth, with the tentacles (generally 40 in adults) extending up to 3–4 m [1,2,3].

These medusae have a greatly varying coloration: colorless, transparent, whitish or yellowish, with mouth-arms of the same colors as the bell. Some also have variously developed radial streaks. Marginal tentacles can be colorless, yellow, red or of intermediate color [2,3].

Contact with C. quinquecirrha tentacles causes normally mild to moderate pain, and medical care may be necessary [2]. The skin rash consists of erythematous wheals and pink spots that may persist for up to one month [1,51].

Given its similarity to Pelagia noctiluca, C. quinquecirrha nematocysts seem also to be activated by vinegar [109]. As for Physalia physalis, nematocyst discharge was found after exposure of a suspension of C. quinquecirrha tentacles to acetic acid (5%), ethanol (70%), ammonia (20%) and bromelain (meat tenderizer), with ammonia having the strongest effect [51].

Ethanol-Benzocaine blends and especially high concentrated (10%–15%) preparations of lidocaine reduced pain and decreased skin redness post-C. quinquecirrha stings. By contrast, exposure to deionized water, meat tenderizer and urea did not produce any benefit [51], and ammonia, ethanol and vinegar increased pain sensation.

Arnold [54] provided weak evidence that papain was effective in treating pain from C. quinquecirrha stings. This result was confirmed by Burnett et al. [46], who performed laboratory tests to assess the effect of different substances on nematocyst discharge from Chrysaora tentacles. High concentrations of meat tenderizer and papain were effective along with Stingose, although rinsing the treated skin exacerbated pain sensation. Conversely, substances found to trigger nematocyst discharge in the latter study were sodium hypochlorite, sodium hydroxide, acetone, vinegar (5%) and ammonia. A very effective remedy to prevent nematocyst discharge was baking soda slurry, unless previous exposure to sodium hypochlorite had occurred. Baking soda is the suggested first line therapy to inhibit nematocyst discharge for Chrysaora stings [42,46].

Cyanea capillata populate waters throughout the world, being found everywhere in Australia, as well as being the most common jellyfish along the Norwegian coast and the North Sea [2,111,112].

The bell of this medusa varies from pink to reddish-gold or brownish-violet, with purple oral arms and reddish or yellow tentacles, hence the common name “Lion’s Mane”. The umbrella ranges from 30 to 80 cm in diameter, in some cases even being almost 2 m [2,111,112].

Stings from C. capillata cause either minor or more severe skin pain/discomfort, and any swelling normally resolves after about 15 min, with erythematous stripes potentially remaining for several days [2].

Systemic symptoms, such as nausea, sweating, abdominal and muscular cramps, may sometimes occur soon after the sting [1]. Detached tentacles are still capable of envenomation.

Vinegar is contraindicated also for C. capillata [112]. Fenner and Fitzpatrick [109] tested Cyanea capillata nematocyst discharge after exposing its tentacles to different solutions of vinegar, methylated spirits and seawater. Vinegar caused discharge, whereas sea water and methylated spirits did not. There was no difference in the results whether the test was conducted on tentacles attached to the medusa or on isolated tentacles. Alcohol, acids and urea were also found to cause nematocyst discharge [109].

In his trial without controls and statistical analysis, Exton et al. [45] reported ice pack application to also be an effective painkiller for C. capillata. Similar to Chrysaora, baking soda is also recommended for Cyanea stings [42]. Therefore, after rinsing with sea water and removing the tentacles, ice application and baking soda is currently considered the primary first aid approach.