Scabies and Pediculosis Pubis: An Update of Treatment Regimens and General Review
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1 SUPPLEMENT ARTICLE Scabies and Pediculosis Pubis: An Update of Treatment Regimens and General Review Karen Wendel 1,3,a and Anne Rompalo Division of Infectious Diseases, Johns Hopkins University School of Medicine, 2 Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, and 3 Baltimore City Health Department Sexual Transmitted Diseases Program, Baltimore, Maryland The ectoparasites scabies and pediculosis pubis are common causes of skin rash and pruritus worldwide. They are transmitted primarily by person-to-person spread and are generally associated with low morbidity. The preferred treatment for scabies has generally been topical agents such as lindane and permethrin. Recently, ivermectin has demonstrated good efficacy in the treatment of scabies, and it may be of particular use in institutional outbreaks and in communities in which scabies is endemic. Combination treatment with topical agents and oral ivermectin may be necessary for crusted scabies. Treatment of pediculosis pubis is best accomplished with topical permethrin, lindane, or pyrethrins with piperonyl butoxide. Although resistance to these topical agents has been reported in head lice, decreased efficacy in the treatment of pediculosis pubis has not been reported. SCABIES Introduction and methods. Scabies is caused by the mite Sarcoptes scabiei var. hominis. The present article provides a brief overview of the characteristics of the mite, the epidemiology of infestation, the manifestations of disease, and diagnosis and treatment. To update current approaches to diagnosis and treatment, we conducted a search of the English-language literature for the dates 1 January June A Medline search was conducted for the terms scabies, Sarcoptes scabiei, Norwegian scabies, crusted scabies, ivermectin, benzyl benzoate, malathion, lindane, and permethrin. AIDSline was searched, excluding Medline listings, for the terms scabies, Sarcoptes scabiei, Norwegian scabies, and crusted scabies. Abstracts from meetings of the Infectious Diseases Society Document prepared for the CDC STD treatment guidelines meeting, Atlanta, Georgia, September a Present affiliation: Oklahoma University Health Sciences Center, Oklahoma City. Reprints or correspondence: Dr. Karen Wendel, Oklahoma University Health Sciences Center, 921 NE 13th St. (111c), Oklahoma City, OK Clinical Infectious Diseases 2002; 35(Suppl 2):S by the Infectious Diseases Society of America. All rights reserved /2002/3508S2-0003$15.00 of America ( ) and the International Society of Sexually Transmitted Diseases Research (1997 and 1999) and the joint meetings of the American Sexually Transmitted Diseases Association and the Medical Society of Venereal Diseases (2000) were reviewed for contributory work. Each study was evaluated for study population, treatment, outcome measures, findings, and potential biases in the study design and analysis. Etiology and epidemiology. S. scabiei was first identified in the early 1600s but was not recognized as the etiology of the skin disorder until the 1700s [1]. The mite is an obligate human parasite that lives in burrowed tunnels in the stratum corneum of the epidermis. It completes its entire life cycle on humans. Pregnant female mites lay eggs in burrows that can be up to 1 cm long and reach to the boundary of the stratum granulosum [2]. In 3 4 days, eggs hatch and the larvae mature on the skin surface. The duration of the life cycle is days. The burden of disease is highest in tropical countries, where scabies is endemic. In other regions, there is limited evidence of a cyclic prevalence of disease. Epidemiological studies in Israeli soldiers and regional studies in England and Denmark have suggested a year cyclic pattern of disease prevalence in these groups [3 6]. A higher burden of disease appears to be S146 CID 2002:35 (Suppl 2) Wendel and Rompalo
2 related to crowded living conditions. Some studies have suggested higher rates in urban areas and an increased incidence during winter months [4 6]. Scabies disproportionately affects women and children [4, 6]. Hospitals, nursing homes, and long-term-care facilities can be sites of epidemic scabies infestations. In 1992, a study that evaluated 130 Canadian long-term-care facilities found that 20% had experienced infestations with scabies during a 1-year period [7]. Facilities that are older, larger, and have a low bed to health care worker ratio have a higher risk of scabies outbreaks [7]. Certain populations are at particularly high risk of developing severe or crusted scabies. This form of hyperkeratotic scabies infection was first described in Norway in patients with leprosy [8]. The risk of developing crusted scabies is increased in patients with organ transplantation, mental retardation, severe physical handicap, systemic or potent topical glucocorticoid use, HIV infection, human T cell lymphotropic virus 1 infection, and various hematologic malignancies [9]. Of interest, crusted scabies is also seen in the Aborigines of rural Australia without identifiable immunocompromise [10]. Clinical manifestations. After initial infection, symptoms can take several weeks to develop. In recurrences, symptoms of pruritus may arise within 24 h [9]. Patients with scabies usually complain of pruritus that is most severe at night, but occasionally patients are asymptomatic. Skin lesions most commonly involve the interdigital spaces, flexor surfaces of the wrist, axillae, waist, feet, and ankles [2]. The area around the nipples of the breast may be affected in women, and the scrotum and penis may be affected in men. The most characteristic lesion of scabies infestation is the burrow, the excavated tunnel in which the mite lives. These are usually thin, curvy, elevated tracts measuring 1 10 mm [2]. Other skin manifestations include papules, blisters, eczematous changes, and nodules [6, 11]. In crusted scabies, the patient s lesions are psoriasiform or warty and can be accompanied by nail hyperkeratosis. The head and neck can be involved, and there may be only mild pruritus. Occasionally there is accompanying eosinophilia and lymphadenopathy [9]. Complications. Scabies is a common dermatosis that usually results in a mild-to-moderate rash with pruritus. However, occasionally significant morbidity is associated with scabies infestation. The extensive lesions of crusted or bullous scabies can be debilitating, with pain on movement and significant breakdown in skin integrity. In northern Australia, a mortality rate of up to 50% over 5 years was reported, with deaths resulting chiefly from secondary sepsis [12]. Secondary bacterial infection is most commonly due to Staphylococcus aureus, group A b-hemolytic streptococci, or peptostreptococci [13]. Several case reports have documented leukocytoclastic vasculitis complicating scabies infection, and one report also noted the presence of lupus anticoagulant [14, 15]. Diagnosis. A presumptive diagnosis of scabies is based on the symptomatic complaint of pruritus accompanied by the physical findings of skin lesions and characteristic scabies burrows. Burrows can be better visualized with mineral oil or ink enhancement or by tetracycline fluorescence tests [2]. Definitive diagnosis requires microscopic identification of mites or their eggs or feces. This is usually obtained by scraping at the site of a burrow or under the patient s fingernails. Other possible strategies for diagnosis include skin biopsy, videodermatoscopy, and epiluminescence microscopy. Videodermatoscopy is performed by use of a video microscope system [16]. In one study, this technique was evaluated and compared with regular skin scraping. Both procedures were performed twice by 2 independent observers. This test can be performed at a magnification of 1000 and takes 5 min to complete. The results of scraping and videodermatoscopy were similar. However, 2 (12.5%) of 16 cases were evident only on skin scraping [16]. Epiluminescence microscopy allows examination of the skin to the level of the superficial papillary dermis [17]. In 65 (92.9%) of 70 cases of scabies, this technique showed dark triangular structures at sites of scabies infection. This technique requires 5 min to perform and has a low false-positive rate [17]. The special diagnostic equipment required for videodermatoscopy and epiluminescence is unlikely to be available at most sites that perform primary evaluation, and they have not been shown to be more sensitive than routine skin scraping. Transmission. Scabies is transmitted by direct skin-to-skin contact. The average host has only 5 10 mites. In crusted scabies, a patient can be infected with millions of mites and is therefore far more contagious [1]. Live mites have been found in dust samples from cases of normal scabies and have been found on floors, furniture, and bedding [18]. For this reason, fomite transmission of disease is considered possible. Some studies have documented the survival of mites for 13 days after separation from their human hosts [19 21]. Treatment. CDC-recommended regimens for the treatment of scabies are presented in table 1 [22, 23]. Other agents for the treatment of scabies include crotamiton, benzyl benzoate, malathion, and sulfur (6%) precipitated in ointment. Formal randomized studies have not addressed the appropriate management of close contacts and contaminated linens and clothing. Most experts recommend that all close contacts and housemates be treated and that all bedding, towels, and clothing be washed in warm to hot water. Items that cannot be washed should be isolated from use for at least 3 days. Since 1996, only 2 randomized controlled clinical trials of scabies treatment have been reported in the English-language literature [24, 25]. Usha and Gopalakrishnan Nair [24] performed a study that addressed the relative efficacy of topical Scabies and Pediculosis Pubis CID 2002:35 (Suppl 2) S147
3 Table 1. CDC-recommended scabies treatment options [22]. Generic name Permethrin 5% (60 g) cream Trade names available in United States Elimite, Acticin; also available as generic Average wholesale price, $US a Instructions for use Apply to whole body from the neck down; wash off after 8 14 h Lindane 1% (60 ml) lotion b Available as generic Apply thinly to the whole body from the neck down; wash off completely after 8 h Ivermectin c (3 mg) Stromectol mg/kg administered orally for 2 doses at an interval of 2 weeks; not an FDA-approved indication NOTE. FDA, US Food and Drug Administration. a Data from 2001 Drug Topics Red Book [23]. b Should not be used immediately after bathing, in patients aged!2 years, in patients with extensive dermatitis, or in pregnant or lactating women [22]. c Not recommended for pregnant or lactating women, and its safety in children weighing!15 kg is unknown [22]. permethrin and oral ivermectin. They found that a single topical dose of permethrin produced a clinical cure rate (97.8%) that was superior to a single dose of oral ivermectin (70%). However, 2 doses of ivermectin separated by 2 weeks were as effective as a single dose of topical permethrin. A comparison of topical lindane and oral ivermectin suggested equivalency between these medications after 2 courses of therapy separated by 2 weeks [25]. The cure rate on clinical evaluation was 96% for lindane and 95% for ivermectin. Several other clinical studies have been conducted. One retrospective comparative study analyzed the outcomes of 39 hospitalized HIV-infected patients with 60 episodes of scabies treated with benzyl benzoate, ivermectin, or a combination of benzyl benzoate and ivermectin [8]. Benzyl benzoate treatment cured 9 (47.4%) of 19 patients, ivermectin cured 10 (62.5%) of 16 patients, and combination treatment cured 4 of 4 patients. Of interest, of the 4 patients with crusted scabies treated with either treatment alone, none were cured. The 4 patients with crusted scabies treated with combination treatment were all cured. This study provides some preliminary evidence for the use of combination treatment for severe disease in HIV-infected patients. Several open-label studies of ivermectin have been published since 1996 in patients with uncomplicated scabies [26 29]. They have used 1 2 doses of ivermectin at 200 mg/kg separated by 7 days. The largest study enrolled 120 patients and demonstrated a clinical response in 88% of patients treated with 1 dose of ivermectin. After 4 weeks and 2 doses of ivermectin, the cure rate rose to 100% [28]. Several other open-label studies have been reported with smaller patient cohorts treated with ivermectin 200 mg/kg (1 2 doses), with cure rates of 76% 100% [26, 27, 29]. These studies included few cases of crusted scabies. In a cohort study, 20 patients with crusted scabies were treated with 1 3 doses of ivermectin at 200 mg/kg combined with a topical scabicide and a keratolytic agent. Eight of 20 had an initial complete response, and 8 of 10 had a response to 3 doses of ivermectin [30]. Finally, in a study of 10 patients with uncomplicated scabies, a complete response was seen in all 10 after 3 4 treatments with topical 1.8% ivermectin cream [31]. In vitro testing of 6 different scabicides (neem, permethrin, benzyl benzoate, ivermectin, lindane, and tea tree oil) showed that all reduced mite survival except neem [32]. However, among the other 5 treatments, mite survival time was longest with permethrin exposure. A clear challenge facing scabies treatment in the future is optimal management in populations with high rates of endemic scabies. One recent study administered community-wide scabies treatment with permethrin and demonstrated a reduction in scabies prevalence from 28% to 7% ( P p.002) at 25 months follow-up. In a village in Papua New Guinea, a single dose of ivermectin 400 mg/kg given to all inhabitants decreased scabies prevalence from 87% to 26% at 5 months follow-up [33]. These studies suggest a role for community-wide treatment to control endemic disease, but further studies will be needed to clarify the long-term impact of these treatments and the economic feasibility. Epidemic scabies in long-term-care facilities was the focus of several additional cohort studies. These studies demonstrated good control of scabies epidemics with 1 2 doses of ivermectin [34, 35]. One of these studies reported success with ivermectin after treatment with several different topical scabicides had failed [35]. Treatment toxicity. There is extensive experience with topical scabicides. Their toxicity profiles are well defined. Both permethrin and benzyl benzoate have been reported to cause rash and diarrhea [36]. More worrisome are the reports of aplastic anemia associated with benzyl benzoate and lindane [37, 38]. According to the World Health Organization 1998 Collaborating Centre for International Drug Monitoring, convulsions have been associated with the use of benzyl benzoate, S148 CID 2002:35 (Suppl 2) Wendel and Rompalo
4 crotamiton, lindane, malathion, and permethrin [39]. Deaths have been reported with crotamiton, lindane, and permethrin [38]. It is thought that warm baths and extensive dermatitis may increase systemic absorption of lindane. Lindane is not recommended for use in pregnant or lactating women, children aged!2 years, or patients with extensive dermatitis. In a randomized controlled trial of lindane and ivermectin treatment, all the reported adverse effects were mild and transient [25]. Patients treated with lindane more frequently complained of headaches, whereas patients treated with ivermectin more frequently noted abdominal pain and vomiting. One patient developed transient hypotension after receiving ivermectin. Rash and a transient increase in pruritus have also been reported in the first 3 days after receiving ivermectin for scabies [27]. Significant side effects to ivermectin have been reported in only one study. That study described an outbreak of scabies in a long-term care facility for the elderly. Patients received multiple applications of topical scabicides before final treatment with a single dose of ivermectin [40]. Over the following 6 months, there was an increased incidence of death in these patients when compared with age- and sex-matched controls. Patients experienced lethargy and anorexia prior to death. There is considerable controversy surrounding the results of this study. Patients were not matched for severity of dementia or other comorbidities [41]. A study, in a psychogeriatric nursing home, compared the mortality rate in the 6 months after ivermectin treatment of scabies to the mortality rate documented the 30 months prior to treatment and found no significant difference [41]. Persistent symptoms. All patients should be informed that the rash and pruritus of scabies may persist for up to 2 weeks after treatment [9]. In situations where symptoms and signs persist 12 weeks, there are several possible explanations. Poor response and presumed resistance to lindane have been described [42, 43]. Treatment failure not related to resistance can be due to faulty application of topical scabicides. Patients with crusted scabies may have poor penetration into thick scaly skin and harbor mites in these difficult-to-penetrate layers. Particular attention must be given to the hyperkeratotic fingernails of these infested patients. Certainly, to avoid reinfection, it is recommended that all close contacts of patients with scabies be empirically treated. All linens, bedding, and clothing should be washed if possible during the time of application of the topical scabicide. Even when treatment is successful and reinfection is avoided, symptoms may worsen secondary to allergic dermatitis. This complication has been seen with topical scabicides. Finally, ordinary household mites may drive persistent symptoms because of cross-reactivity between antigens. In a study of 25 patients, patients with scabies had higher skinprick tests and IgE levels to house dust mite and storage mite antigen than did controls [44]. PEDICULOSIS PUBIS Introduction and methods. Lice are blood-sucking insects that have no free-living stage in their life cycle [45]. Lice infest primarily the head (Pediculus humanus var capitis), the body (Pediculus humanus var corporis), or the pubic region (Pthirus pubis). In the present article, we will summarize key features of pediculosis pubis and update current approaches to diagnosis and treatment. A search of the English-language literature was conducted for the dates from 1 January 1996 to 30 June A Medline search was performed for the terms pubic lice, Pthirus pubis, pediculosis, pediculosis pubis, permethrin, and lindane. AIDSline was searched, omitting Medline listings, for the terms Pthirus pubis, pediculosis, and pediculosis pubis. Abstracts from meetings of the Infectious Diseases Society of America ( ), the International Society of Sexually Transmitted Diseases Research (1997 and 1999), and the joint meetings of the American Sexually Transmitted Diseases Association and the Medical Society of Venereal Diseases (2000) were reviewed for contributory work. For each study, the following characteristics were defined: study population, treatment, outcome measures, findings, and potential biases in the study design and analysis. Treatment trials for head lice were included in our findings. Lice characteristics. P. pubis is 1 3 mm long and has 3 pairs of legs [9]. The life cycle of the female insect is 1 3 months. The adult female lays up to 300 eggs that adhere to hair at the skin hair junction. Eggs or nits hatch in 6 10 days. These nymphs then mature to adults within 10 days. P. pubis infests hair in the pubic area and occasionally areas of strong body hair. They will rarely infest eyebrows and eyelashes. Diagnosis and transmission. Pediculosis pubis is diagnosed by the identification of live lice and/or viable nits. The most common symptom of lice infection is pruritus. Physical findings include visible opalescent nits or live lice and blue macules (maculae caeruleae) at feeding sites. All patients with P. pubis should have a thorough investigation for other sexually transmitted diseases. Transmission is by direct intimate contact [9]. Fomite transmission is unlikely to play a significant role. Treatment. Treatment regimens for pediculosis pubis are listed in table 2 [22, 23]. In addition to topical treatments, all bedding, towels, and clothing should be washed. Patients should be instructed to avoid contact with their sexual partners until they have been evaluated for pediculosis pubis. Some patients may require a second application of topical therapy 3 7 days after the initial treatment [46]. Infestation of eyelashes should be treated with the application of an occlusive ointment Scabies and Pediculosis Pubis CID 2002:35 (Suppl 2) S149
5 Table 2. CDC-recommended treatment regimens for pediculosis pubis [22]. Generic name Trade names available in United States Average wholesale price, $US a Instructions for use Permethrin 1% (60 ml) cream Acticin; also available as generic 8.19 Apply to affected areas and wash off after 10 min Lindane 1% (60 ml) shampoo b Available as generic Apply to affected areas and wash off thoroughly after 4 min Pyrethrins with piperonyl butoxide (60 ml) shampoo a Data from 2001 Drug Topics Red Book [23]. b Not recommended for pregnant or lactating women or children aged!2 years [22]. such as Vaseline twice a day for 10 days [22]. Other agents which may be effective in treatment of P. pubis are malathion 0.5%, carbaryl 0.5% 1%, and phenothrin 0.2% [46]. Since 1996, there have been no new treatment trials published concerning the treatment of P. pubis. There were, however, 5 clinical treatment trials for head lice. In a comparative trial of sumithrin and lindane, sumithrin demonstrated a clearance rate of 86.8% 96% [47]. Lindane had a clearance of 67.5%. A randomized blinded clinical trial that compared permethrin and pyrethrum extract enrolled 150 patients and demonstrated 100% efficacy in both treatment groups at 7 days [48]. There was no significant difference in combing time per nit. Treatment of head lice in children in Taiwan demonstrated a success rate of 93.4% 97.3% with bioallethrin, malathion, or permethrin [49]. One study assessed both in vitro susceptibility of lice and in vivo response to topical lice treatment in children in Bath and Bristol, England. Both cohorts of children had lice that demonstrated a decreased fatality rate to permethrin and malathion [50]. Children in Bath were treated with malathion with a 36% cure at h. Children in Bristol were treated with permethrin and had a 13% cure at h. The sample size of this study was only 30 children, but it suggests the presence of head lice with dual resistance to permethrin and malathion in these cohorts. Further in vitro evaluations were performed by Pollack et al. [51], who sampled head lice from children in Massachusetts, Idaho, and Malaysian Borneo. They found that US lice had 50% mortality in response to permethrin. The fatality rate was unaltered by increasing concentrations of drug. Conversely, the lice from Malaysia had a 37% mortality rate at the lowest concentrations of permethrin. Their fatality increased linearly with increasing permethrin concentrations, to a maximum mortality rate of 95%. This study suggests the possible emergence of drug resistance in US head lice. The concern raised by these results is amplified by another in vitro analysis that demonstrated that lice with permethrin resistance also have resistance to sumithrin and a newer agent for treatment, deltamethrin [52]. The emergence of drug resistance in head lice throughout the world is worrisome, but the implications for Multiple brand-name products available!10.00 Apply to affected area and wash off after 10 min treatment of P. pubis are unclear. Since 1996, there have not been any studies in the English language that have documented significant treatment failure in the management of P. pubis. DISCUSSION Ectoparasites continue to be a common cause of skin disease throughout the world. Topical agents are generally effective in management but are occasionally accompanied by serious side effects, and resistance can occur. Ivermectin represents a new oral mode of treatment for scabies and may hold particular promise in the treatment of epidemic or severe scabies. Combination treatment with ivermectin and topical scabicides may prove to be the best treatment for crusted scabies, but this requires further study. P. pubis is usually effectively treated with topical agents, but rising rates of drug resistance in head lice warrant concern regarding the future efficacy of current topical agents in the treatment of pediculosis pubis. References 1. Mathisen GE. Of mites and men lessons in scabies for the infectious diseases clinician. Clin Infect Dis 1998; 27: Burkhart CG, Burkhart CN, Burkhart KM. An epidemiologic and therapeutic reassessment of scabies. Cutis 2000; 65: Mimouni D, Gdalevich M, Mimouni FB, Haviv J, Ashkenazi I. The epidemiologic trends of scabies among Israeli soldiers: a 28-year followup. Int J Dermatol 1998; 37: Christophersen J. The epidemiology of scabies in Denmark, 1900 to Arch Dermatol 1978; 114: Kimchi N, Green MS, Stone D. Epidemiologic characteristics of scabies in the Israel Defense Force. Int J Dermatol 1989; 28: Downs AM, Harvey I, Kennedy CT. The epidemiology of head lice and scabies in the UK. Epidemiol Infect 1999; 122: Holness DL, DeKoven JG, Nethercott JR. 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