Copyright # Blackwell Publishing, Inc., 2002

Dermatologic Therapy, Vol. 15, 2002, 10±17 Printed in the United States
All rights reserved

DERMATOLOGIC THERAPY ISSN 1396-0296

Skin problems related to noninfectious coastal microorganisms WILLIAM A. BURKE*

&

PATRICIA A. TESTERy

*Department of Dermatology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, and yNational Ocean Service, National Oceanic and Atmospheric Administration, Center for Coastal Fisheries and Habitat Research, Beaufort, North Carolina

ABSTRACT: While there are a number of coastal microorganisms that can cause infections of the skin, there are many that can cause skin problems that are noninfectious in nature. From cyanobacterial dermatitis to skin problems related to dinoflagellates, to skin signs of ciguatera or scombroid fish poisonings, to ``sea lice''/``seabather's eruption,'' to ``swimmer's itch,'' this article attempts to separate these entities into distinct syndromes caused by a variety of bacteria, phytoplankton and zooplankton. Treatment and prevention of these diseases are also discussed. KEYWORDS: bites and stings, ciguatoxin, cyanobacteria, Dinoflagellata, marine toxins, Pfiesteria piscicida, schistosomatidae.

There are many noninfectious cutaneous problems that are caused by aquatic microorganisms such as bacteria, phytoplankton, and zooplankton. While some of these problems are relatively insignificant and require only symptomatic care and reassurance, a few may be fatal. It is important for clinicians to recognize the varied signs and symptoms of these diseases based on a proper history and physical examination, as well as having a basic understanding of the causative microscopic flora and fauna. Skin problems related to bacterial skin infections are covered elsewhere in this issue, and only noninfectious microorganisms will be discussed here.

Address correspondence and reprint requests to: William A. Burke, MD, Department of Dermatology, Brody School of Medicine, East Carolina University, 600 Moye Blvd., Brody 3E113, Greenville, NC 27858-4354, or e-mail: burkew@mail. ecu.edu.

10

Cyanobacteria (blue-green algae) Cyanobacteria (blue-green algae) are prokaryotic, chlorophyll-containing, microscopic filamentous and nonfilamentous organisms found in freshwater, estuarine, and marine environments. These organisms proliferate in areas of high nutrient overload and can form blue-green, milky-blue, green, red, or dark-brown ``blooms'' or ``scums'' (1). While not all cyanobacteria are toxic, some species such as Lyngbya, Microcystis, Anabaena, Aphanizomenon, Cylindrospermopsis, Nodularia, and Oscillatoria/Trichodesmium (Fig. 1) have been shown to produce toxins which may be relatively harmful (1±4). These toxins can be hazardous to human and animal health and have been responsible for sporadic animal (mammals, birds, fish) fatalities (5). Cyanobacterial toxins may be tumor promoters, hepatotoxins, neurotoxins, or skin irritants (6,7). Human illness related to cyanobacteria and their toxins may be via direct contact (recreational or other) or ingestion (of water, fish, or

Noninfectious coastal microorganisms

Fig. 1. Filaments of Trichodesmium, a cyanobacterium (blue-green alga) (original magnification 200).

shellfish). In a hemodialysis unit in Brazil, 126 patients became seriously ill and 60 of them died when water from a lake contaminated with cyanobacterial toxins (microcystins) was used at the unit (8). Deaths were primarily from liver failure, and ecchymoses were seen in some of these patients (8). Skin reactions from cyanobacterial toxins were initially reported from the organism Lyngbya majuscula, which secretes lyngbyatoxins which can be irritating to skin and mucous membranes, causing irritant dermatitis and conjunctivitis (9,10). This filamentous organism blooms into algal mats which cover surface waters when a high nutrient load occurs. Periods of high winds and flooding rains can cause these mats to flow into coastal and estuarine waters where wave action breaks the mats apart into individual microscopic filaments. Bathing suits on persons swimming in affected waters filter and collect microscopic toxin-secreting cyanobacterial filaments under the suits. As the swimmer leaves the water and the water from the bathing suit evaporates, toxins are concentrated and skin irritation (at times with blistering) may occur, most commonly in areas covered by the bathing suit. Eye stings and conjunctivitis have also been reported (11). Blistering skin reactions around the mouth have also been reported possibly due to microcystins after contact with water containing toxic Microcystis aeruginosa (12). Affected individuals had many other signs and symptoms, including malaise, fever, cough, pleuritic chest pain, abdominal pain, nausea, vomiting, confusion, and pneumonia. It is important to take a careful history when a patient presents with possible cyanobacterial skin eruptions in order to make a

presumptive diagnosis. Recreational and occupational exposure as well as possible ingestion need to be considered. There is no proven therapy for cyanobacterial toxicity. Treatment of systemic disease is with supportive care, and symptomatic care with antihistamines and topical steroid creams is often used for the cutaneous component (11,12). Removal of the bathing suit and showering quickly after leaving the water is important in prevention of the dermatitis. Eye stings should be treated with irrigation with tap water followed by ophthalmologic consultation (11). Skin stings and rashes from cyanobacteria have been given many names: ``algae dermatitis,'' ``seabather's eruption,'' ``stinging limu,'' and ``seaweed dermatitis.'' To avoid confusion, it seems reasonable to term skin eruptions due to toxic cyanobacteria simply ``cyanobacterial dermatitis.''

Estuarine and marine phytoplankton Unicellular eukaryotic phytoplankton can cause skin reactionsÐsome when ingested and some on skin contact. A variety of intoxications may occur when various endotoxin-producing marine phytoplankton (dinoflagellates, as well as a marine diatom) are filtered and concentrated by shellfish and later ingested by people. These shellfish poisoning syndromes include paralytic shellfish poisoning, neurotoxic shellfish poisoning, amnesic shellfish poisoning, and diarrhetic shellfish poisoning. While these intoxications can be severe and some may lead to death, they generally do not affect the skin (13±15). Ciguatera fish poisoning is caused by eating fish which have bioconcentrated the tropical/ subtropical epiphytic reef-associated Gambierdiscus toxicus dinoflagellate in their tissue. Several other epiphytic dinoflagellates have also been implicated. With approximately 50,000 cases annually throughout the world, this disease has become the most common illness related to consumption of finfish, primarily due to exportation of fish from tropical/subtropical areas to other parts of the world (16,17). Fish commonly implicated include mackerel, jacks, coral trout, barracuda, grouper, flowery cod, snapper, reef sharks, moray eel, wrasse, and others (16±21). Ciguatoxin, maitotoxin, and other toxins associated with G. toxicus are lipid soluble and cold/ heat stable. Ciguatera poisoning usually presents within 3±6 hours after ingestion as gastroenteritis

11

Burke & Tester

(diarrhea, abdominal pain, nausea, and vomiting) and neurologic symptoms (weakness, headache, tremor, ataxia) (20,21). Paresthesia of the extremities and circumoral area as well as hot-cold temperature reversal are symptoms frequently seen in ciguatera toxicity, and can help separate this illness from other causes of gastroenteritis. Skin problems include severe pruritus (which is a common complaint and which can last for years) (16) and rarely chronic urticaria. Death is quite rare, but may occur due to cardiopulmonary arrest. Treatment of the acute toxicity is with mannitol infusion (1 g/kg intravenously over 30±45 minutes) (22,23). Chronic symptoms are treated with amitriptyline, tocainide, mexiletine, nifedipine, and gabapentin (24±27). Another dinoflagellate, Karenia brevis (previously known as Gymnodinium breve) (Fig. 2), can develop into huge blooms called ``red tides,'' because of the reddish discoloration it causes in affected water. This organism produces endotoxins that have been classified as brevetoxins. These toxins can cause massive fish kills, and when filtered and concentrated by shellfish and then ingested, neurotoxic shellfish poisoning. K. brevis migrate to the upper part of the water column and are transported throughout the Gulf of Mexico and the U.S. South Atlantic Bight by major current systems (Fig. 3) (28).

Fig. 2. Karenia breve, a ``naked dinoflagellate,'' is the primary causative agent of the ``red tide'' blooms. (Photo courtesy of Steve Kibler, National Oceanic Service, NOAA.)

12

Fig. 3. Sea surface temperature satellite imagery of the Gulf Stream (dark red) which serves as a method of transport to distribute Karenia brevis blooms from the Gulf of Mexico to the U.S. South Atlantic Bight. (Photo courtesy of NOAA.)

Unlike most dinoflagellates, K. brevis is a ``naked'' dinoflagellate and lacks polysaccharide protective plates of armor. Because of this, heavy wave action and surf can cause its cell membranes to rupture, thereby releasing and aerosolizing the endotoxins (29). As the toxins are very irritating to skin and mucous membranes, it can cause an irritant dermatitis, conjunctivitis, pharyngitis, rhinorrhea, sneezing, coughing, and dyspnea (17,29). As the toxins also cause smooth muscle contraction, wheezing and asthma may also occur, and this can be a major problem for persons who have already been diagnosed with asthma (30±32). As there is no effective treatment for skin and mucous membrane problems related to K. brevis (except for symptomatic care), avoidance and removal of oneself away from the beach is the best course, as symptoms are quickly reversed. Induced asthmatic attacks are treated with bronchodilators. Another dinoflagellate that has been recently implicated as causing symptoms and skin lesions in humans is Pfiesteria piscicida (Fig. 4). Discovered in 1988 in a university laboratory as a cause of fish kills (33), workers working with cultures of this organism reported problems with concentration and memory, emotional lability, and skin lesions, as well as variety of other symptoms (34). Various life cycle stages are purported to be toxin producing. Unlike other dinoflagellates, Pfiesteria is reported to secrete exotoxins that enter the water, but are not thought to enter the food chain. While the lay press has spread much misinformation about Pfiesteria causing skin ulcerations

Noninfectious coastal microorganisms

and mid-Atlantic United States, and will hopefully shed some light on this controversial topic in the near future (38). There is no known treatment for possible Pfiesteria/PCO-related illness. Symptoms of ``burning'' when exposed to estuarine waters resolve rapidly with washing with tap water or within 12 hours without treatment (36). Use of visual contrast as a screening tool for Pfiesteria/ PCO-related illness (39) and use of cholestyramine in treatment (39±41) should currently be viewed as anecdotal.

Fish poisonings and the skin

Fig. 4. Scanning electron micrograph of the heterotrophic dinoflagellate Pfiesteria piscicida. Ventral view of planozygote. (Photo courtesy of Dr. Karen A. Steidenger, Florida Marine Research Institute.)

and sores in humans, scientific data is lacking. In a Maryland study (35) of persons felt to possibly have a Pfiesteria-related illness, a variety of skin ailments were identified, but most were thought to be unrelated to Pfiesteria exposure (36). A few cases of erythematous papules and patches that were nondiagnostic were of a mild nature. One symptom that appeared to be significant was the sensation of skin ``burning'' on contact with water (36). Several other dinoflagellates, such as cryptoperidiniopsoid species ``brodyi,'' Pfiesteria schumwayae, and others, appear similar to P. piscicida when visualized with a light microscope, and this group of organisms has been termed Pfiesteria-complex organisms (PCOs). Whether some of these PCOs are capable of causing human health problems is currently under investigation. In order to study illnesses in humans possibly due to Pfiesteria and PCOs, a set of criteria for what is now termed ``possible estuary-associated syndrome'' (PEAS) has been established by the Centers for Disease Control (CDC) (Table 1) (37). Currently Pfiesteria/PCO toxins have not been identified, isolated, or purified in quantities that would allow for diagnostic testing. Because of this, proof that PEAS is a real syndrome caused by this group of dinoflagellates is currently not available. A six-state prospective study of this is in progress in the southeastern

Ciguatera is a major cause of fish poisoning in humans, but as it is due to a toxic dinoflagellate, it is discussed above. Another common cause of fish poisoning which can affect the skin is termed scombroid poisoning or histamine fish poisoning. This syndrome is caused by bacteria which contain the enzyme histadine decarboxylase and which proliferate in improperly stored histadinerich fish. These bacteria break down histadine to histamine which, when ingested, leads to a histamine intoxication syndrome (42). Fish implicated in histamine poisoning include tuna, bonito, albacore, mackerel, wahoo, sardines, anchovies, herring, dolphin fish (mahi mahi), amberjack, yellowtail, redfish, bluefish, marlin, and salmon (42±45). Degradation of histadine generally occurs when the fish are not properly chilled after being caught. Rapid chilling of fish on the fishing vessel and keeping the temperature lower than 0C throughout its distribution is the best way to prevent unwanted histamine

Table 1. CDC criteria for possible estuaryassociated syndrome (PEAS) (37) Persons are considered to have PEAS if: 1. They report developing symptoms within 2 weeks after exposure to estuarine water. 2. They report memory loss or confusion of any duration and/or three or more selected symptoms (i.e., headache, skin rash at the site of water contact, sensation of burning skin, eye irritation, upper respiratory irritation, muscle cramps, and gastrointestinal symptoms) that, with the exception of skin rash at the site of water contact and sensation of burning skin, persist for 2 weeks or more. 3. A health care provider cannot identify another cause for the symptoms.

13

Burke & Tester

formation (45). Once formed, histamine is heat stable and is not affected by cooking. Symptoms of histamine poisoning occur 30±60 minutes after ingestion and include flushing, abdominal cramps, diarrhea, headache, hyperhidrosis, urticaria, pruritus, heart palpitations, nausea, vomiting, angioedema, and rarely, bronchospasm. Transient visual loss has also been reported (46). Death is rare but may occur. This syndrome may be misdiagnosed as anaphylaxis, monosodium glutamate sensitivity, ciguatera poisoning, seafood allergy, and Salmonella infection (42,44). Treatment of histamine fish poisoning is, as one would expect, with antihistamines, both H1 (diphenhydramine, hydroxyzine, promethazine) and H2 antagonists (cimetadine, ranitidine). Subcutaneous epinephrine, bronchodilators, and systemic corticosteroids may occasionally be needed. Without treatment, the disease is usually self-limiting and subsides within 8±12 hours. There are many other types of fish poisoning, including pufferfish, ichthyotoxic, hallucinatory, Haff disease, clupeoid, ichthyohemotoxic, barracuda, and others (47). These diseases only rarely affect the skin and are beyond the scope of this article.

Estuarine and marine zooplankton (``sea lice,'' ``seabather's eruption'') Estuarine/marine zooplankton from a variety of phyla can cause pruritic, bitelike or stinging sensations of the skin of people in the water. Often collectively termed ``sea lice'' or ``seabather's eruption,'' these reactions are usually caused by a wide and diverse group of microorganisms. Some marine zooplankton such as some crab larvae have sharp spines (Fig. 5) (48), which, when concentrated by filtering in a bathing suit, can lead to pruritus and skin irritation similar to a fiberglass dermatitis (49,50). Microscopic copepods as well as tiny isopods and amphipods can also cause pruritus if large numbers are filtered by the bathing suit and then the person leaves the water. In addition, some isopods and cymothoids contain strong biting mouth parts as well as chitinous setae on their legs which allow them to closely adhere to human skin while biting (51). While this is relatively insignificant and feels like the bite of a gnat or biting fly, it can lead to erythematous hemorrhagic lesions and may be of

14

Fig. 5. A crab zoea, which contains sharp spicules that can irritate human skin.

concern to bathers. These organisms are generally fish parasites or feed on dead decaying plant material. The microscopic larvae of cnidarians can cause stinging sensations while swimming in waters where these occur. Larvae of some jellyfish, sea anemones, and even small hydroids have been suggested as causative and, like cyanobacterial dermatitis, this has also been termed ``sea lice'' and ``seabather's eruption'' (52±56). Lesions can vary from erythematous macules and papules (Fig. 6) to vesicular or urticarial reactions. These usually begin 2±24 hours after exposure. Depending on the causative organism, both covered and uncovered areas of skin may be affected. The rash and pruritus usually lasts for 3±7 days, with more severe cases lasting up to 6 weeks (57). Occasionally, systemic reactions may occur with nausea, vomiting, diarrhea, malaise, headache, weakness, myalgias, arthralgias, and, especially in children, fever. The eruption usually begins with a stinging or ``prickly'' sensation while in the water. The thimble jellyfish (Linuche unguiculata) as well as a sea anemone larva (Edwardsiella lineata) have been implicated (52±58). While some of the stinging sensation in the water might be due to

Noninfectious coastal microorganisms

Cercarial dermatitis (``swimmer's itch,'' ``clam-diggers itch,'' ``duck itch'')

Fig. 6. ``Sea lice'' or ``seabather's eruption'' can be caused by a wide variety of aquatic microorganisms and may involve covered or uncovered areas of skin.

nematocyst activation, immunologic hypersensitivity may also occur, as sera from affected persons may show specific reactivity to the organism (59). Risk factors for developing this condition include young age (less than 16 years), prior history of a similar rash, and surfing (60). Jellyfish tentacles which have been broken apart by wave action during storms can also cause stinging sensations and a rash. This has also been termed ``sea lice.'' Removal of the bathing suit and showering as soon as possible after leaving the water can be helpful in prevention. Use of specific topical lotions and protective barrier creams can, at this point, be viewed as only anecdotal. Otherwise treatment is generally symptomatic with antihistamines and menthol-containing lotions. In cases with severe itching, immunologic mechanisms may play a role, and use of topical and even systemic steroids may be helpful.

More commonly seen in fresh or brackish water, cercarial dermatitis is caused by microscopic cercarial flatworms, which can be present in the water in large numbers and can penetrate human skin. These larvae have difficulty penetrating cloth, and the resulting rash is therefore found primarily on uncovered areas of skin (Fig. 7). Waterfowl (especially ducks and geese), as well as some mammals, are the usual hosts for these parasitic flatworms. Their ciliated miracidia parasitize aquatic snails, which are usually found in areas of abundant aquatic vegetation (61). The flatworms attach themselves to human skin via a sucker and often begin their penetration into the skin as the skin dries after leaving the water (47). Cutaneous irritation begins as a ``prickly'' sensation in affected areas, and pruritus worsens as the cercariae burrow further into the skin. As man is an accidental host when animal schistosomes invade the skin, the parasite dies (usually within 24±48 hours). In animal cercarial dermatitis, a papular eruption occurs at the site of penetration and may disappear over days, or the patient may develop an intensely pruritic papular or papulovesicular eruption, which is thought to be due to a delayed hypersensitivity reaction. The rash may last weeks and then resolve (61,62). The pruritic rash may be more severe with repeated exposure, but is only very rarely associated with systemic symptoms or fever (61).

Fig. 7. Cercarial dermatitis is caused by microscopic flatworms that have difficulty penetrating cloth, and the cutaneous eruption typically involves uncovered areas of skin.

15

Burke & Tester

Vigorous toweling immediately after leaving the water and prior to skin drying may remove some of the cercariae and may lessen the skin response. Wearing protective gloves when reaching into the water, boots when wading, and a swim skin or wet suit while swimming or diving may be helpful in reducing the extent of the rash. When the rash initially occurs, symptomatic treatment with antihistamines and menthol-containing lotions may be helpful. In delayed hypersensitivity reactions with pruritus, topical and systemic corticosteroid medications are used (63). It must be remembered that human visceral schistosomiasis (bilharziasis) is endemic in parts of Asia, the Middle East, Africa, South America, and the West Indies, and here the parasite penetrates the skin, moves to the bloodstream, and produces eggs. The eggs then pass to the bladder and intestines and are passed into the urine or stool. The organisms can invade numerous organs. Urine, stool, and more recently, blood tests can assist in diagnosis, and treatment varies with both the organism and the region. Oxamniquine, praziquantel, and metrifonate are used in treatment (64). Copper sulfate, formaldehyde, and other helminthicides and molluscacides have been suggested in controlling these parasites in ponds and small lakes; however, widespread use of these agents has been discouraged due to environmental concerns.

Conclusion There are many noninfectious aquatic microorganisms that can cause skin symptoms, lesions, rashes, and at times, systemic illness and rarely death. A better understanding of the many microscopic bacteria, plants, and animals that can lead to illnesses in humans is crucial to understanding the many diseases they produce.

References 1. Elder GH, Hunter PR, Codd GA. Hazardous freshwater cyanobacteria (blue-green algae). Lancet 1993: 341: 1519±1520. 2. Soong FS, Maynard E, Kirke K, Luke C. Illness associated with blue-green algae. Med J Aust 1992: 156: 67. 3. Lagos N, Onodera H, Zagatto PA, Andrinolo D, Azevedo SM, Oshima Y. The first evidence of paralytic shellfish toxins in the freshwater cyanobacterium Cylindrospermopsis raciborskii isolated from Brazil. Toxicon 1999: 37: 1359±1373.

16

4. New understanding of algae. Environ Health Perspect 1999: 107: A13. 5. Codd GA, Ward CJ, Bell SG. Cyanobacterial toxins: occurrence, modes of action, health effects and exposure routes. Arch Toxicol 1997: 19(suppl): 399±410. 6. Bell SG, Codd GA. Cyanobacterial toxins and human health. Rev Med Microbiol 1994: 5: 256±264. 7. Codd GA. Cyanobacterial toxins: occurrence, properties and biological significance. Water Sci Technol 1995: 32: 149±156. 8. Pouria S, deAndrade A, Barbosa J, et al. Fatal microcystin intoxication in haemodialysis unit in Caruaru. Brazil Lancet 1998: 352: 21±26. 9. Grauer FH, Arnold HL Jr. Seaweed dermatitis. Arch Dermatol 1961: 84: 62±74. 10. Aimi N, Odaka H, Sakai S, et al. Lyngbyatoxins B and C: two new irritants from Lyngbya majuscula. J Nat Prod 1990: 53: 1593±1596. 11. Thomas C, Scott S. All stings considered. Honolulu: University of Hawaii Press, 1997. 12. Turner PC, Gammie AJ, Hollinrake K, Codd GA. Pneumonia associated with contact with cyanobacteria. Br Med J 1990: 300: 1440±1441. 13. Van Dolah FM. Marine algal toxins: origins, health effects, and their increased occurrence. Environ Health Perspect 2000: 108(suppl 1): 133±141. 14. Trevino S. Fish and shellfish poisoning. Clin Lab Sci 1998: 11: 309±314. 15. Committee on Environment and Natural Resources. National assessment of harmful algal blooms in US Waters. Washington, DC: National Science and Technology Council, 2000. 16. Lehane L. Ciguatera update. Med J Aust 2000: 172: 176±179. 17. Baden DG, Fleming LE, Bean JA. Marine toxins. In: deWolff FA, ed. Handbook of clinical neurology. New York: Elsevier Science, 1995:141±175. 18. Morris PJ, Campbell DS, Freeman JI. Ciguatera fish poisoning: an outbreak associated with fish caught from North Carolina coastal waters. South Med J 1990: 83: 379±382. 19. Sakamoto Y, Lockey RF, Krzanowski JJ Jr. Shellfish and fish poisoning related to the toxic dinoflagellates. South Med J 1987: 80: 866±872. 20. Caplan C. Ciguatera fish poisoning. Can Med Assoc J 1998: 159: 1394. 21. Lange WR. Ciguatera fish poisoning. Am Fam Physician 1994: 50: 579±584. 22. Palafox NA, Jain LG, Pinano AZ, Gulick TM, Williams RK, Schatz IJ. Successful treatment of ciguatera fish poisoning with intravenous mannitol. JAMA 1988: 259: 2740±2742. 23. Pearn JH, Lewis RJ, Ruff T, et al. Ciguatera and mannitol: experience with a new treatment regimen. Med J Aust 1989: 151: 77±80. 24. Bowman PB. Amitriptyline and ciguatera. Med J Aust 1984: 140: 802. 25. Lange WR, Kreider SD, Hattwick M, Hobbs J. Potential benefit of tocainide in the treatment of ciguatera: report of three cases. Am J Med 1988: 84: 1087±1088. 26. Calvert GM, Hryhorczuk DO, Leikin JB. Treatment of ciguatera fish poisoning with amitriptyline and nifedipine. J Toxicol Clin Toxicol 1987: 25: 423±428. 27. Perez CM, Vasquez PA, Perret CF. Treatment of ciguatera poisoning with gabapentin. N Engl J Med 2001: 344: 692±693.

Noninfectious coastal microorganisms 28. Tester PA, Steidinger KA. Gymnodinium breve red tide blooms: initiation, transport, and consequences of surface circulation. Limnol Oceanogr 1997: 42: 1039±1051. 29. Coleman BA, Doetsch RN, Sjoblad RD. Red tide: a recurrent marine phenomenon. Sea Frontiers 1986: 32: 184±192. 30. Asai SA, Krzanowski JJ Jr, Lockey RF, et al. The site of action of Ptychodiscus brevis toxin within the parasympathetic axonal sodium channel H gate in airway smooth muscle. J Allergy Clin Immunol 1984: 73: 824±828. 31. Watanabe T, Lockey RF, Krzanowski JJ Jr. Airway smooth muscle contraction induced by Ptychodiscus brevis (red tide) toxin as related to a trigger mechanism of bronchial asthma. Immunol Allergy Prac 1988: 10: 25±32. 32. Shimoda T, Krzanowski J Jr, Nelson R, et al. In vitro red tide toxin effects on human bronchial smooth muscle. J Allergy Clin Immunol 1988: 81: 1187±1191. 33. Smith SA, Noga EJ, Bullis RA. Mortality in Tilapia aurea due to a toxic dinoflagellate bloom. Proceedings of the Third International Colloquium on Pathology in Marine Aquaculture. Gloucester Point, VA; Virginia Institute of Marine Sciences, 1988:167±168. 34. Glascow HB, Burkholder JM, Schmechel DE, Tester PA, Rublee PA. Insidious effects of a toxic estuarine dinoflagellate on fish survival and human health. J Toxicol Environ Health 1995: 46: 501±522. 35. Grattan LM, Oldach D, Perl TM, et al. Learning and memory difficulties after environmental exposure to waterway containing toxin-producing Pfiesteria or Pfiesteria-like dinoflagellates. Lancet 1998: 352: 532±539. 36. Lowitt MH, Kauffman CL. Pfiesteria and the skin: a practical update for the clinician. Md Med J 1998: 47: 124±126. 37. Centers for Disease Control and Prevention. Notice to readers: possible estuary-associated syndrome. MMWR 1999: 48: 381. 38. Smith CG, Music SI. Pfiesteria in North Carolina: the medical inquiry continues. N C Med J 1998: 59: 216±219. 39. Shoemaker RC, Hudnell HK. Possible estuary-associated syndrome: symptoms, vision and treatment. Environ Health Perspect 2001: 109: 539±545. 40. Shoemaker RC. Pfiesteria: crossing dark water. Pocomoke City, MD: Dr. Richie Shoemaker, 1998. 41. Shoemaker RC. Diagnosis of Pfiesteria-human illness syndrome. Md Med J 1997: 46: 521±523. 42. Lehane L. Update on histamine fish poisoning. Med J Aust 2000: 173: 149±152. 43. Burnett JW. Histamine poisoning. Cutis 1990: 46: 388. 44. Mandojana RM. Aquatic dermatology. In: Demis DJ, ed. Clinical dermatology. Philadelphia: Lippincott-Raven, 1995.

45. Becker K, Southwick K, Reardon J, Berg R, MacCormack JN. Histamine poisoning associated with eating tuna burgers. JAMA 2001: 285: 1327±1330. 46. McInerney J, Sahgal P, Vogel M, Rahn E, Jonas E. Scombroid poisoning. Ann Emerg Med 1996: 28: 235±238. 47. Edmonds C. Dangerous marine creatures. Frenchs Forest, New South Wales: Reed Books, 1989. 48. Costlow JD Jr, Bookhout CG. The larval development of Callinectes sapidus Rathbun reared in the laboratory. Biol Bull 1959: 116: 373±396. 49. Burnett HW, Burnett PJ, Burnett JW. Cutaneous irritation produced by oceanic crab larvae. Cutis 1999: 63: 208. 50. Burnett JW, Cargo DG. Cutaneous irritation induced by crab larvae. J Am Acad Dermatol 1979: 1: 42±43. 51. Best WC, Sablan RG. Cymthoidism (sea louse dermatitis). Arch Dermatol 1964: 90: 177±180. 52. Tomchick RS, Russell MT, Szmant AM, Black NA. Clinical perspectives on seabather's eruption, also known as ``sea lice.''. JAMA 1993: 269: 1669±1672. 53. Parrish DO. Seabather's eruption or diver's dermatitis? JAMA 1993: 270: 2300±2301. 54. Freudenthal AR, Joseph PR. Seabather's eruption. N Engl J Med 1993: 329: 542±544. 55. Sullivant R. Little jellyfish, big rash. Sea Frontiers 1993: 39: 16±17. 56. Sams WM. Seabather's eruption. Arch Dermatol Syph 1949: 60: 227±237. 57. Basler RS, Basler GC, Palmer AH, Garcia MA. Special skin symptoms seen in swimmers. J Am Acad Dermatol 2000: 43: 299±305. 58. Segura-Puertas L, Ramos ME, Aramburo C, Heimer de la Cotera EP, Burnett JW. One Linuche mystery solved: all 3 stages of the coronate scyphomedusa Linuche unguiculata cause seabather's eruption. J Am Acad Dermatol 2001: 44: 624±628. 59. Wong DE, Meinking TL, Rosen LB, Taplin D, Hogan DJ, Burnett JW. Seabather's eruption: clinical histologic and immunologic features. J Am Acad Dermatol 1994: 30: 399±406. 60. Kumar S, Hlady WG, Malecki JM. Risk factors for seabather's eruption: a prospective cohort study. Public Health Reports 1997: 112: 59±62. 61. Chapman A, Ekelund C, Tominaga J. Rash and pruritus after a camping trip. Pediatr Infect Dis J 1993: 12: 966±969. 62. Mulvihill CA, Burnett JW. Swimmer's itch: a cercarial dermatitis. Cutis 1990: 46: 211±213. 63. Centers for Disease Control. Cercarial dermatitis outbreak at a state park: Delaware, 1991. MMWR 1992: 41: 225±228. 64. Cioli D. Chemotherapy of schistosomiasis: an update. Parasitol Today 1998: 14: 418±422.

17