Papular Urticaria and Things that Bite in the Night Jeffrey G. Demain, MD, FAAAAI Address external pressure, which might result in slowing of blood Allergy, Asthma & Immunology Center of Alaska, 2741 DeBarr Road, flow, thereby enhancing precipitation of immune complexes C-405, Anchorage, AK 99508, USA. [1]. Papules might also have a more diffuse, generalized dis- E-mail: [email protected] tribution involving the torso, neck, and face. The distribu- Current Allergy and Asthma Reports 2003, 3:291–303 tion of lesions serves as an important clue in identifying the Current Science Inc. ISSN 1529-7322 Copyright © 2003 by Current Science Inc. culprit arthropod (Table 1). Papules are erythematous, rang- ing from 3 to 10 mm. In the clinical setting, lesions are often excoriated and secondarily infected, contributing to the Whether we are hiking in the back country or playing in our characteristic intense pruritis. Perennial or seasonal exacer- backyard, we run the risk of exposure to offending arthro- bations are common and are presumed to be associated pods. Papular urticaria is a very common hypersensitivity with re-exposure to the offending arthropod. Recurrence of reaction to the bites, stings, and contact with critters such as papular urticaria with re-exposure seems to lessen in adoles- mites, ticks, spiders, fleas, mosquitoes, midges, flies, and even cence and adulthood. This might reflect the development of caterpillars. Children seem to be at greatest risk, although immune tolerance toward the antigenic proteins [2,3] adults are also vulnerable. The classic presentation of papular Arthropods, including mosquitoes, flies, gnats, mites, urticaria includes recurrent pruritic papules or vesicles and ticks, and caterpillars, have been linked to papular urti- varying degrees of local edema. Severity is often related to caria. Penneys et al. [4] demonstrated human antibody the host response to the salivary or contactant proteins. binding to salivary gland and foregut endothelial protein Our understanding of the immune mechanism continues to antigen in mosquitoes. Distinct stages of evolving mos- improve; however, our approach to therapy has remained quito-bite immunity have been described (Table 2): I) essentially unchanged. Although this review admittedly induction; II) delayed reaction alone; III) immediate reac- reaches beyond papular urticaria, it is with the intention of tion with delayed reaction; IV) immediate reaction alone; improving the reader’s recognition of the offending arthro- and V) lack of immediate or delayed reaction [4–7]. In pods, the characteristics of reactions, and the current thera- unexposed subjects, there is no reaction to the first bite. peutic approaches. Both the delayed and the immediate reactions account for the ensuing papular urticaria. Previously sensitized sites also erupt following the appearance of new lesions, sug- Introduction gesting that circulating antigen triggers the reactivation of Papular urticaria is a manifestation of recurrent pruritic sensitized sites [8]. papules or vesicles and varying degrees of local edema. The pathogenesis and exact immune mechanisms of pap- Reactions are thought to be the result of a hypersensitivity ular urticaria remain somewhat unclear. Heng et al. [3] reaction to biting, stinging, or urticating insects. The sev- reported granular deposits of C1q, C3, and IgM in the superfi- erity of the eruption and pruritis are related to the host cial dermal vessels in three subjects with papular urticaria, response to the salivary or contactant proteins. Children suggesting that immune complexes with complement activa- seem to be predisposed to papular urticaria; possibly a tion through the classic pathway might be involved in the reflection of immune mechanisms and/or behaviors that pathogenesis. A subsequent study by Jordaan and Schneider facilitate the encounters with the offending critters. It is no [9] of 30 patients with papular urticaria failed to demonstrate surprise that a seasonal predilection during spring and deposition of IgA, IgG, IgM, C3, or fibrin by direct immuno- summer is commonly reported, although perennial exac- fluorescence. Immunochemistry results revealed abundant T erbations also occur. lymphocytes and macrophages. Yoshikawa [10] reported the Typically, papules are grouped in clusters on exposed histology of lesions produced by Chelacaropsis spp. mites in areas, particularly extensor surfaces of extremities and con- six subjects. After 48 to 72 hours of exposure, biopsies of stricting areas such as the tops of socks and around waist- lesions revealed perivascular aggregation of mononuclear bands. In some cases, papules follow a vascular distribution. cells and slight edema of the papillary dermis [2,3,9,10]. It has also been postulated that papules around constricted Although the lesions and pattern of papular urticaria areas might represent the effects of local factors, such as are characteristic, other conditions based on presentation 292 Allergic Dermatosis and Urticaria Table 1. Distribution of papular urticaria as a diagnostic tool Arthropod Exposed area Ventral surfaces Constricting band (waist, sock) Generalized Mosquito Yes No No No Flies Yes No No No Gnats Yes No No No Scabies Yes No No No Other mites Yes Yes Yes No TicksNoNoYesNo Lepidoptera Yes No Yes No Adapted from Millikan [5]. Table 2. Classification of human mosquito-bite reported as envenomation. Hymenoptera, snakes, spiders, reaction and scorpions (in descending order) accounted for 79% of deaths from envenomation, with Texas having the highest Stage Immediate Delayed number of venomous deaths. Many deaths caused by arthro- INoNo pods go unrecognized as such because the signs of envenom- II No Yes ation are not noticed. Other arthropods, such as reduviids III Yes Yes and caterpillars, might be the source of severe toxic as well as IV Yes No allergic reactions in humans. VNoNo Contact with arthropods is no longer limited to endemic Adapted from McCormack et al. [7]. regions. Venomous arthropods are often transferred inad- vertently by shipments of goods. This is best demonstrated by the introduction of the imported red fire ant, Solenopsis and/or histologic features should be considered. Included invicta, into the United States from Brazil. In 1939, fire ants in the differential are atopic dermatitis, contact dermatitis, entered the United States on infested produce [19] and adverse drug reactions, “id” reaction, varicella, miliaria again, in the 1950s, they entered on an unregulated ship- rubra, polymorphous light eruption (PMLE), Giannoti- ment of azaleas [20]. The imported fire ant now infests more Crosti syndrome, linear IgA bullous dermatosis, and pityri- than 160 million acres in 13 states. Further illustrating this asis lichenoides. Features distinguishing papular urticaria point are three cases of scorpion envenomation in Michi- include distribution (clustered or grouped papules), pat- gan. Scorpions arrived as stowaways in camping equipment tern of recurrence, and histopathology [2]. from Arizona and again in infested citrus shipments from Arthropoda, “joint-footed animal,” is the largest phylum Florida [21]. Worldwide travel for business, tourism, and in the animal kingdom. It accounts for approximately 80% military service has also placed offending arthropods and of the animals and encompasses more than 1.5 million subjects together [17,19–21,100]. described species [11]. Arthropods have a dual economic impact. They provide a source of food and pollination, but also destroy crops, food, clothing, and shelter. The medical Arachnida impact on humans includes transmission of disease as well The class Arachnida includes 65,000 species identified by as morbidity and mortality associated with immune-medi- their four pairs of jointed legs, segmented bodies, large cepha- ated and toxic reactions after exposure to salivary protein, lothorax, and hardened (chitinized) exoskeleton. There are venom, excrement, or body parts. Millions of individuals several species that attack humans. Skin invasion can provide are affected annually [11–18,100]. a meal or a site for larval development. Through envenoma- Venomous arthropods are found in every state in the con- tion or salivation, they can cause pronounced local or sys- tinental United States. In addition to papular urticaria, insects temic symptoms [21]. and arthropods are responsible for more severe, IgE-mediated reactions. These reactions can be limited to a cutaneous event, Mites such as urticaria, or cause generalized, as in life-threatening More than 30,000 species of mites and ticks make up the anaphylaxis. IgE-mediated reactions present with immediate arachnid subclass Acari. Of these, approximately 50 species of reactivity, usually within minutes, and are often followed by a mites are capable of causing lesions in human skin. These subsequent, late-phase reaction, as long as several hours later. blood-feeding arthropods are important vectors of pathogens, Parrish [16] reviewed the death certificates of people whose most of which are transmitted in saliva, spreading diseases deaths were recorded as animal-related fatalities from 1950 to such as scrub typhus, endemic typhus, western equine 1959. He found 460 people whose cause of death was encephalomyelitis, and rickettsial pox. Cutaneous reaction to Papular Urticaria and Things that Bite in the Night • Demain 293 mites is usually papular or vesicular, with intense pruritis. The days. In addition to the patient, all family members and saliva of the mite has