W. Cary Mobley, BS Pharmacy, PhD

• Clinical Associate Professor
• College of Pharmacy
• University of Florida

Parasitological confirmation of the diagnosis should be made in all cases if possible medications names purchase 4 mg detrol with visa. It has been shown that sensitivity of this technique was 91% and specificity 86% [49] symptoms diarrhea detrol 1mg overnight delivery. However medicine identifier pill identification purchase detrol no prescription, the external validity of this monocentric study performed with trained investigators needs to be confirmed in other centres treatment conjunctivitis discount 4 mg detrol with amex. Dermoscopy is less timeconsuming than skin scraping procedure because it allows a quick screening of a large number of sites symptoms zenkers diverticulum purchase detrol 1 mg amex. However medications and grapefruit 2mg detrol visa, the use of dermoscopy is limited by the cost of the dermoscope and the sensitivity may decrease in inexperienced hands. After firmly applying the adhesive side of the tape onto an appropriate skin lesion of patients, the tape is pulled off and transferred directly onto a slide for microscopy, affixing the adhered separated part of the corneal skin. This tape method is simple and may be useful for diagnosis of severe scabies infestation in longterm nursing units [50]. These new methods (dermoscopy and adhesive tape test) may increase the sensitivity of skin scraping tests and limit false negative results [49,51]. However, comparing the accuracy of different tests for diagnosing scabies remains elusive without a criterion standard [52,53]. A skin biopsy may confirm the diagnosis of scabies if a mite or parts can be identified. However, in most cases, the histology shows nonspecific features, with epidermal spongiosis, papillary oedema, and superficial and deep perivascular inflammatory cell infiltrates with numerous eosinophils [54]. Management [8,12,16,44,58,59,60,61,62,63] Indication for therapy Treatment should be prescribed to the patient and close physical contacts, even without pruritus or cutaneous lesions. Patient education Patients should be advised to avoid close physical contact until they and their household members and sexual partners have been treated. A detailed verbal and written information about scabies infestation should be given to the patient [64]. Treatment options Topical and oral products are available although rigorous studies to guide their use are lacking. Topical treatment includes permethrin, lindane, benzyl benzoate, esdepallethrine (bioallethrin), crotamiton and precipitated sulphur. Despite the varied methodological quality of trials, a recent metaanalysis suggested that topical permethrin is the most effective [61]. In one recent trial in which two doses of permethrin were compared with a single dose of ivermectin, only a small and nonsignificant advantage was observed with permethrin (93 versus 86%) [68]. Oral ivermectin interrupts the aminobutyric acid induced neurotransmission of many parasites including mites, but is not licensed for use in scabies in most countries. Because ingestion of food increases the bioavailability of ivermectin by a factor of 2 [72], taking it with food might enhance the penetration of the drug into the epidermis. Many of the reported adverse effects have occurred in individuals given ivermectin for the treatment of filariasis, in whom serious reactions were thought to be related to death of the parasites [73]. In the absence of confirmed mites, diagnosis is currently based entirely on clinical and epidemiological findings. Given the extensive differential diagnoses, the specificity of clinical diagnosis is poor, especially for those inexperienced regarding scabies [46]. Furthermore, there are the difficulties in distinguishing between active infestation, residual skin reaction and reinfestation. Despite the relatively low sensitivity of diagnostic testing, empirical treatment is not recommended for patients presenting with generalized itching [12]. Therefore some authors consider the drug must be contraindicated in children less than 5 years of age or under 15 kg, and during lactation. Finally, permethrin or ivermectin may be used for the treatment of classical scabies. Oral ivermectin is more expensive and not licensed in most countries; however, this agent may be preferred for patients who cannot tolerate topical therapy or are unlikely to adhere to a therapeutic regimen [12,63]. In classical scabies, the combination of topical therapy and oral ivermectin has never been compared with either treatment alone. Materials or fomites that cannot be washed should be treated with insecticidal products. However, it is possible that patients receiving oral ivermectin remain contagious longer than those receiving topical therapies [12,63]. Benzyl benzoate and esdepallethrine are safe in children <2 years of age, but duration of use should be limited to 12 h. If topical treatment is chosen, antibiotherapy against Streptococcus pyogenes and Staphylococcus aureus should be performed before. Permethrin, benzyl benzoate and sulphur appear to be safe in pregnancy, although the evidence is limited [87]. The management of institutional outbreaks is mainly based on consensus expert opinion. It requires coordination and adequate education of all involved personnel and a sustained effort to rapidly control the outbreak. Prompt recognition of the index case, formation of an outbreak management team, determining the extent of the outbreak and risk factors for transmission, immediate implementation of infection control Additional measures Examination and laboratory investigation to search for sexually transmitted infection should be performed as scabies is considered to be a sexually transmitted disease [60]. Topical treatment must be applied to the entire skin surface, including the scalp, all folds, groin, navel and external genitalia, as well as the skin under the nails. Treating the face of babies is essential because transmission may occur by breastfeeding. Hands should not be washed during therapy, otherwise the treatment should be reapplied. If topical treatment is applied by another person, it is recommended that this person wears protective gloves. Followup Itching may persist several weeks after scabies, and this should be clearly explained to the patient. Crusted scabies is a rare and severely debilitating form of the disease, characterized by the infestation of up to millions of mites and the development of hyperkeratotic skin crust. An undiagnosed case of crusted scabies may be the source of an outbreak of common scabies. Causes Cutaneous irritation Overtreatment Eczematization Contact dermatitis Poor compliance: inappropriate or insufficient treatment Resistance to scabicide Reinfestation or relapse Delusions of parasitosis Management Intensive use of emollient Intensive use of emollient Topical steroid Further scabicide application Treatment failure Change scabicide Further scabicide application Antipsychotic drugs (prescribed by dermatologists and/or psychiatrists) Treat the underlying cause pathophysiology [5,6] In common scabies, there are few mites, probably because scratching destroys the burrows. Crusted scabies occurs in people with an inadequate immune response to the mite, allowing them to multiply. It is a severe disease with a significantly higher morbidity than ordinary scabies. Patients who are mentally retarded or suffer from dementia may develop crusted scabies [7], and Down syndrome is a frequent association [3,8]. The reason for this association with mental abnormality is not completely understood, but lack of appreciation of pruritus may be important. Crusted scabies has also resulted from the use of topical steroids [21] and pimecrolimus [22]. Crusted scabies sometimes occurs in otherwise healthy individuals [23,24], and in northern Australia, where crusted scabies is a problem in the Aboriginal population, 42% of a series of 78 patients had no identifiable risk factors [25]. Erythema Psychogenic pruritus Nonparasitic dermatosis Adapted from Chosidow 2000 [14]. A keratolytic agent such as a salicylic acid preparation should be used to treat hyperkeratosis. Expert consensus recommends combining topical and oral therapy [35], although this has never been evaluated. Topical scabicide application should be repeated until two parasitological tests 3 days apart become negative. The administration schedule of ivermectin should be based on the severity of infection [40]; between three and seven doses have been proposed [27]. Recently, a simple clinical grading scale to aid in the management of patients with crusted scabies has been proposed and may be useful [42]. Management If contact with animal scabies is suspected, the diagnosis can only be confirmed by examining and taking scrapings from the suspect animal. Human skin lesions are selflimiting, and will resolve once exposure to the affected animal has ceased, or it has been treated. Despite being selflimited, the skin eruption may be uncomfortable, and topical treatment such as 5% permethrin cream will hasten recovery [20]. Oral ivermectin (200 g/kg single dose) has been used [20,21], as well as topical corticosteroids, menthol preparations, and oral antihistamines for symptomatic relief [22]. Family Knemidokoptidae Knemidokoptes mutans causes scaly leg in domestic poultry, and Mesoknemidokoptes laevis is a closely related mite which causes depluming itch in poultry; both have caused skin lesions in humans [1]. Family Sarcoptidae: animal scabies Family Psoroptidae introduction and general description Transmission of animal scabies to humans is probably rare, because of the relative host specificity of the mites [1]. However, recurrent exposure to animal scabies mites can produce troublesome and diagnostically puzzling lesions. Many varieties of Sarcoptes scabiei have been incriminated, including the following. Exceptionally, scrapings from human skin have shown mites and eggs, and symptoms have persisted after contact with the animal has ceased [15]. Affected animals have areas of scaling and hair loss on the ears, face and limbs [17]. Species of Chorioptes and Psoroptes from cattle, horses and sheep have occasionally affected humans [1,2]. Otodectes cynotis is a common parasite in the ears of cats and dogs, and has been discovered in the ears of a patient suffering from otitis externa [3,4]. It was also considered to be responsible for a pruritic dermatosis in a patient whose dog was infested. The distribution of the dermatitis is dependent upon the areas that come in close contact with the animals [5]. Family Listrophoridae Listrophorus gibbus, a common parasite of the domestic rabbit [6], has been reported as causing papular urticaria in a child [7]. The extent of the erythroderma and the warty plaques varies greatly, and either may predominate. Crusted scabies may be localized, affecting only the scalp, face, fingers, toenails or soles [28]. Generalized lymphadenopathy is present in some cases, and blood eosinophilia and elevated IgE levels are common. Crusted scabies may masquerade as hyperkeratotic eczema, psoriasis, Darier disease [29], contact dermatitis [30] and Langerhans cell histiocytosis [31]. The diagnosis is readily confirmed by examination of scrapings, which will be teeming with mites and eggs. Clinical features Skin lesions resulting from contact with animal scabies vary in extent and distribution, according to the mode of exposure. The eruption is usually composed of small pruritic weals or papules, which are frequently excoriated, and resemble human scabies, but without burrows. Lesions from exposure to sarcoptic mange in dogs and notoedric mange in cats usually occur at sites of contact with the animal, principally the chest, abdomen, thighs and forearms. In addition to respiratory allergy, skin lesions can occur, secondary to bites or contact with allergens. Herbivorous and fungivorous, they subsist on fungi and are pests of stored food products with high moisture content. The appearance of the eruption on the face may suggest an acute contact dermatitis. Housedust mites introduction and general description Dermatophagoides pteronyssinus, the housedust mite, was first discovered by Trouessart in dust shaken from tanned mammal skins [1]. It was subsequently established that it is widely distributed in the human environment in house dust and beds [2,3]. Part 3: InfectIons & InfestatIons epidemiology It occurs worldwide, and has been reported from all inhabited continents [4]. It is commonly associated with Euroglyphus maynei and Dermatophagoides farinae, which are related species in the same family, the Pyroglyphidae. Classification Family Acaridae these mites attack flour, grain, dried meat, cheese and dried fruit. Acarus siro is the most important pest of storage premises, and is found on flour, grain and, occasionally, cheese. Suidasia nesbitti is particularly associated with wheat pollards and bran, and has been recorded as causing dermatitis in humans [8].

Investigations Despite the short incubation period treatment type 2 diabetes best buy detrol, air travel may carry infected individuals to any part of the world medicine x 2016 generic detrol 2 mg online. Specific agglutinins in a titre over 1: 100 must be regarded as suspicious and over 1: 300 as diag nostic medications mobic purchase generic detrol. The histological changes in the skin lesions [1] are usually not dis tinctive medicine xalatan purchase detrol 4mg visa, but there may be intense inflammatory changes around vessels showing gross intimal proliferation medications used to treat migraines discount 2 mg detrol with visa, and granuloma for mation may occur treatment low blood pressure best order for detrol. Causative organisms the organism, a Gramnegative aerobic coccobacillus, colonizes the cells of the reticuloendothelial system and induces a granu lomatous tissue response. The lymph nodes and spleen are enlarged in about 50% of cases and the liver in about 25%. The recommended course of treatment for brucellosis now includes doxycycline and rifampicin, both of which should be given for at least 6 weeks. An alternative com bination regimen is streptomycin and tetracycline, and the use of oxytetracycline plus gentamicin for an initial period of 5 days has been successful in children over the age of 8 years. Veterinary surgeons, and others who are in frequent contact with infected animals, may develop a high degree of allergic sensitivity to Brucella antigens. Secondary eruptions of erythema multiforme type may develop remotely from the sites of contact. Differential diagnosis For most cases, brucellosis should be considered in the diagnosis of fevers of unknown origin. In contact brucellosis, transmissible diseases including herpes simplex and zoster as well as zoonoses such as orf and poxvirus infections should be considered. The illness usually lasts for 3 or 4 months, but both acute fulminating and extremely chronic forms occur. In the latter, there may be persistent infection of the bone, gall bladder or other organs. Introduction and general description the human diseases associated with these organisms are trench fever due to B. There is usually no leukocytosis but there may Part 3: InfectIons & InfestatIons management 26. Bartonella species may also remain in endothelial cells in a vacuolelike structure called an invasome. In many cases, it is believed that the cat is the source of the organism and the wound is the portal of entry. A scratch by a cat fulfils both requirements and is the common est mode of infection. In a study of 1200 cases, it was found that while a bite or scratch from another animal may provide a route for infection, a feline source could nearly always be identified [6]. The diagnosis may easily be missed in mild cases, and subclini cal infection may be frequent if skin test surveys are valid, which give a 4% positive result in the general population, 18% in the families of patients and 23% in veterinary surgeons. Part 3: InfectIons & InfestatIons epidemiology It has been diagnosed in many different countries, usually under conditions where there have been very poor levels of hygiene. Most cases have a widespread maculopapular eruption, most prominent on the trunk, which fluctuates with the fever. Disease course and prognosis the illness is usually mild with spontaneous recovery. Presentation In between 3 to 5 days after the inoculating event, a papule (occa sionally a group of papules) may form which progresses through vesicular and crusting stages in 2 or 3 days, and may ulcerate. This lesion may be inconspicuous, or may take several weeks to regress and then often leaves a superficial scar. Its identification is of diag nostic importance, and by diligent searching, including examina tion of the scalp, ears and fingers, the inflammatory lesion or a residual scar can be found in over 90% of cases. Con stitutional symptoms are usually mild, but fever is present in 60% of cases, persisting for a few days or 1 or 2 weeks. Lymphadenopathy is present in all cases, and usually develops within 1 or 2 weeks of the initial papule, although it may not be noticed until later. The affected node is in the drainage path of the primary lesion but there is no lymphangitis. Uncommonly, bilateral lymphadenopathy is seen, but this can be explained by separate inoc ulations or a single one close to the midline. The glands are painful and tender and occasionally progress to suppuration and discharge before regressing in a period of weeks or months; persistent enlarge ment is uncommon. Cat scratch disease Definition and nomenclature Infection due to Bartonella (previously Rochalimea) henselae [3,4]. Patients with the syndrome usually have antibodies to this organism, which has also been isolated from lymph nodes. The same organism also causes a chronic form of bacteraemia in cats without any apparent ill effects. Clinical variants Primary inoculation of the eye, which does not require injury, causes a granulation, usually painless, and usually on the pal pebral conjunctiva, followed by enlargement of the preauricular gland, constituting one of the forms of Parinaud oculoglandular syndrome [9]. Unusual cutaneous manifestations include a maculopapular rash, urticaria, thrombocytopenic purpura, erythema nodosum, Age It affects all ages, but mostly children and teenagers; 87% of 1200 cases were aged 18 years or under [6]. It is characterized by the development of friable angiomatous papules and nodules. The appearance of these lesions follows a septicaemia, which is usually mild and often passes unnoticed. Complications and comorbidities Rarely, there may be systemic involvement [6,8] with arthritis, osteolytic lesions, intraabdominal or intrathoracic lymphad enopathy, encephalopathy [10], myelitis [11], radiculitis, cerebral arteritis [12], pneumonia, pleurisy or granulomatous infection of the liver or spleen. In the uncomplicated case, there may be a poly morphonuclear leukocytosis and a slight elevation of the erythro cyte sedimentation rate. Disease course and prognosis Cat scratch disease, even when accompanied by the more severe complications, is benign and selflimiting. Introduction and general description the disease presents with small proliferative blood vessel contain ing lesions on the skin surface. A history of a cat scratch days or weeks previously resulting in a granuloma tous nodule distal to the gland would immediately confirm the diagnosis, and the importance of actively seeking these two features has been emphasized [6]. Primary tuberculosis, other mycobacterial infections, lymphogranuloma, pyogenic adenitis and sporotricho sis must be considered, and in the absence of a visible inoculation lesion, lymphoma or sarcoidosis must also be excluded. The infection is sporadic and there is not necessarily a history of exposure to cats or of skin injury. Pathology [6,7] Both the primary lesions and the regional lymph nodes show char acteristic, although nonspecific, changes. In the early stages, there is focal reticulum cell hyperplasia, which forms granulomas of the sarcoid type. Later, there are microabscesses surrounded by a pali sade of epithelioid cells and occasionally Langhans giant cells. Immunohistochemistry demonstrates the bacilli in the inoculation lesion or, more commonly by the time of presentation, in the lymph node, and would confirm the diagnosis. However, the organisms are increasingly difficult to detect as the disease progresses. Skin testing with cat scratch disease antigen made from pus from affected lymph nodes has its advocates [6] but is not generally advised. The bacteria can enter red blood cells and are thought to stimulate angiogenesis in the vascular endothelium. There are no known differences between skin infections caused by the two species of Bartonella. Fluctuant glands may be aspirated, but should not be incised as chronic drainage may occur. Excision of lymph nodes is not justified therapeutically, although it may occasionally be indi cated for histology. They may be solitary or appear in crops, as small papules of dermal Part 3: InfectIons & InfestatIons 26. There is lobular proliferation of small blood vessels that con tain swollen endothelial cells. Age In the endemic areas, most individuals are infected in childhood and acquire a permanent immunity. Again, the endothelial cells lining these spaces contain large num bers of organisms. Pathology the disease is transmitted by sandflies of the genus Lutzomyia and the bacteria are introduced into the bloodstream through an insect bite. Persisting forms in circulating cells act as a reservoir for new infections spread by sandflies. The bacteria can also pen etrate endothelial cells in vitro and produce an endothelial cell stimulating factor. Disease course and prognosis the skin lesions remain if the patient does not receive treatment. Lesions have to be distinguished from those of pyogenic granulo mas, molluscum contagiosum, Kaposi sarcoma and deep fungal infections disseminated to the skin. Presentation Two forms of infection are recognized: Oroya fever and ver ruga peruana; these are now known to represent two stages of infection. In the first stage (Oroya fever) there is a sudden onset of pyrexia accompanied by a rapidly progressive, haemolytic anaemia. Hepatosplenomegaly and generalized lymphadenopa thy occur and a petechial or ecchymotic rash may develop. Verruga peruana may develop without previous Oroya fever, or may follow it weeks or months later. The eruption is com posed of erythematous papules, which appear in crops and often become nodular or pedunculated. They are most numerous on the face, neck and limbs but may also involve the mucous membranes. Mild constitutional symptoms and fever coexist in this form of infection, which may settle spontaneously. One characteristic is that they may be present in different stages of evolution in the same patient [21]. Oroya fever and verruga peruana Definition and nomenclature [19] Oroya fever is an infectious disease transmitted by Phlebotomus spp. Differential diagnosis the appearance of the typical verrucous lesions is typical although other conditions such as disseminated deep mycoses should be considered. Disease course and prognosis Oroya fever is potentially fatal with a high case fatility rate. Environmental factors There is a related seasonal infection caused by and spread through Ixodes ticks called human granulocyte anaplasmosis and caused by a closely related organism Anaplasma phagocytophylum. Investigations the diagnosis should be considered only if the patient has visited the endemic areas. Verruga peruana must be distinguished from yaws, acquired haemangiomas and Kaposi sarcoma. The biopsy appearances of verruca peruana show lesions con taining numerous small blood vessels with endothelial prolifera tion. There is a variable infiltrate of chronic inflammatory cells, and lesions heal with fibrosis [22]. In Oroya fever, the organism can be seen in blood films or iso lated in blood cultures. Blood cultures are also positive during the active phase of the benign form, and in skin biopsies B. The median incubation period is 7 days and patients generally present with fever, malaise, headache and myalgia. Over 30% of patients have a diffuse maculopapular rash and in some this becomes petechial [3]. Clinical variants Ehrlichia sennetsu infections that occur rarely in the Far East are similar in presentation, although rashes are uncommon [5]. In Oroya fever, chloramphenicol 2 g/day for a week is the treat ment of choice because of the frequent coexisting Salmonella infec tion, but B. In verruca peruana, response to antibiotics is unsatisfactory; most lesions evolve and eventually settle uninfluenced by treatment. Differential diagnosis It is important to distinguish ehrlichiosis from Rocky Mountain spotted fever, in which more patients develop a rash. Formerly associated predominantly with infection in domestic and wild animals, a human form of the dis ease has been recognized more recently as a tickborne zoonosis. Actinobacillus actinomycetemcomitans is frequently isolated from lesions of actinomycosis along with the usual Actinomycete cause, giving rise to the view that it is involved in the pathogenesis of this condition [1]. These bac teria are inhabitants of water and cause infections in fish and reptiles. Aeromonas hydrophila is sensitive to cotrimoxazole and chloramphenicol, but usually resistant to ampicillin and other penicillins.

Injectable penicillins are generally preferred to oral preparations because of problems of patient compliance and uncertain absorption from the gastro intestinal tract treatment 4 syphilis discount 2 mg detrol visa. Adequate treatment requires the maintenance of serum concentrations in excess of 0 medications 319 order detrol 2 mg with amex. Treatment of late syphilis theoretically may require a longer duration of therapy because organisms are dividing more slowly symptoms for strep throat cheap 4mg detrol mastercard, but the validity of this concept has not been addressed treatment 3rd degree hemorrhoids buy detrol online. For treatment of neurosyphilis treatment of ringworm order detrol overnight, high dosages of crystalline benzyl penicillin G medicine 93 7338 buy generic detrol on-line, plus probenicid, should be considered. In patients who are hypersensitive to penicillin, regimens based on tetracycline, doxycycline, erythromycin and chloramphenicol have all been successfully used to treat syphilis; however, success is less assured than with penicillin. Azithromycin, given in dosages of 500 mg daily for 10 days, or in a single 2 g dosage, has recently been successful, but there are concerns about the emergence of antimicrobial resistance [97,98]. Many clinicians advocate a short course of corticosteroids to lessen its effects in these patients. Nontreponemal antibody test titres correlate with disease activity and will usually become negative with time after successful treatment. Apart from up to 25% of patients treated for primary syphilis, the treponemal antibody tests will continue to remain positive after successful treatment. Quantitative nontreponemal serological testing is repeated at 3 and 6 months, and each 6 months thereafter. In cases of serological or clinical relapse, retreatment with double doses is recommended. In neurosyphilis it is usual to Penicillin reactions Accidental deaths following treatment are very rare and mainly due to anaphylactic shock reactions to penicillin. Headache, myalgia, bone pains and an exacerbation of skin lesions may accompany the fever. Retreatment should be considered if the cell count shows an inadequate response or if all of these parameters have not returned to normal by 2 years. In cases of serological or clinical relapse, retreatment with double penicillin doses is recommended. Patients treated for neurological or cardiovascular syphilis should be followed up for many years. If untreated during pregnancy, syphilis can lead to fetal loss or stillbirth or, in a live born infant, neonatal death, prematurity, low birth weight and infant disorders such as deafness, neurological impairment and bone deformities. It is largely preventable by good prenatal care and timely penicillin treatment [1,2]. Introduction and general description Management of sexual contacts It is recommended that attempts be made to identify, trace and offer further investigation to atrisk sexual contacts. In early syphilis, these are contacts occurring within 3 months plus the duration of symptoms for primary syphilis, within 6 months plus the duration of symptoms for secondary syphilis and within 1 year for early latent disease. All longterm partners of patients with late syphilis should be offered investigation. Many clinicians recommend presumptive treatment of all sexual contacts within the 90day period preceding patient presentation of early syphilis if serological test results are not immediately available and if followup cannot be assured. Epidemiology Incidence and prevalence Precise data on the incidence of congenital syphilis among live born infants are limited, especially for countries without surveillance or reporting systems. Up to onethird of women attending antenatal care clinics are not tested for syphilis. It estimated that annually there are approximately 215 000 still births or early fetal loss, 90 000 cases of neonatal death, 65 000 cases of low birth weight and 150 000 infections in newborns that occur as a result of syphilis infections among pregnant women [4,5]. An enhanced surveillance study is being undertaken to accurately estimate the incidence of congenital syphilis, identify factors associated with cases of congenital infection and inform efforts to improve health care systems to ensure that women and their babies are managed appropriately [7]. The majority of cases will present during childhood although the diagnosis in some may not be made until adulthood. Congenital syphilis Definition Congenital syphilis results from transplacental passage of Treponema pallidum from an infected pregnant woman to her fetus but may also occur during delivery in the presence of maternal Sex the disease is seen equally in both sexes. Cases reflect the socioeconomic status and adequacy health care systems in their countries of origin. A wide spectrum of severity exists, and only severe cases are clinically apparent at birth. The placenta may show proliferative vascular changes and there may be acute inflammation of the umbilical cord (funisitis) [10]. In about twothirds of untreated cases, clinical signs may begin to appear in the third to eighth week of life. Early congenital syphilis can manifest as rhinitis with serosanguinous nasal discharge, vesiculobullous eruptions of the skin, oral mucous patches, bony abnormalities, chorioretinitis and visceral lesions. It manifests as a profuse, serous, nasal discharge that contains a high concentration of T. Individual lesions, which can be relatively large, can typically be seen on the extremities, especially the palms and soles. The bullae most commonly occur on the red, infiltrated palms and soles; their serous contents contain abundant active treponemes. The syphilitic Pathology the histological lesion of congenital syphilis, as with acquired syphilis, is that of obliterative endarteritis, consisting of mononuclear and plasma cell infiltration surrounding the blood vessels with intimal hyperplasia and swollen, hyperplastic endothelial cells. Fibrosis can be relatively fine in character, consisting of collagen disposition around the blood vessels, or it may distort and replace the parenchyma of the affected organ. Liver, kidneys, bone, pancreas, spleen, lungs, heart and brain are most frequently affected. The severity is variable ranging from lifethreatening involvement of multiple organs to isolated radiological or laboratory abnormalities [9]. Congenital syphilis can be divided into: 1 Early disease presenting within the first 2 years of life. It shows as a very tender, painful swelling and may lead to Parrot pseudoparalysis. Visceral lesions causing pneumonia alba, hepato and splenomegaly, sometimes with jaundice, are common, as is anaemia and thrombocytopenia [12]. Meningitis and meningoencephalitis with convulsions have been described, with bulging of the fontanelle, neck stiffness and, later, hydrocephalus and severe intellectual impairment. Late congenital syphilis the manifestations of late congenital syphilis represent the consequences of the inflammatory response at the sites of treponemal infection during the early stages of the disease. Late congenital syphilis can present as a variety of skeletal developmental defects and a characteristic facies. The common problem is to differentiate latent or late acquired syphilis from late congenital syphilis. A thorough history, including antibiotic history and clinical examination is needed to establish a diagnosis of late congenital syphilis. Late congenital syphilitic eruptions of the skin and mucous membranes can closely resemble nodular syphilides, gummata and periostitis of late acquired syphilis. They are of great diagnostic importance as they generally appear in children from 5 to 16 years of age. There is spotty or diffuse clouding of the cornea, with pronounced ciliary and pericorneal injection. Brushlike vessels are seen penetrating from the sclera into the deeper layers of the cornea, which is best seen with a slit lamp [15]. Periostitis of the long bones is common, particularly of the tibiae, which may become thickened and bent Part 3: InfectIons & InfestatIons 29. Tinnitus and vertigo are common prodromal symptoms and may continue and accompany the increasing perceptive deafness. Stigmata Scars and defects caused by congenital syphilis have diagnostic importance in distinguishing it from acquired syphilis. One of the characteristic stigmata of congenital syphilis is deformity of the upper, central incisor teeth [21]. The incisors are conical or barrel shaped, with a degree of notching at the free edge. Investigations (a) the diagnosis of congenital syphilis can prove to be difficult for the following three reasons: 1 T. Part 3: InfectIons & InfestatIons First line Infants and children who require treatment for syphilis but who have a history of penicillin allergy or develop an allergic reaction presumed secondary to penicillin, should be desensitized, if necessary, and then treated with penicillin [24,25]. The following four scenarios describe the treatment for infants aged under 1 month diagnosed with congenital syphilis, while scenario 5 relates to older infants and children. Scenario 5 In older infants and children the recommended regimen is aqueous crystalline penicillin G 0. Second line Data are insufficient regarding the use of other antimicrobial agents. Nontreponemal antibody titres should decline by the age of 3 months and should be nonreactive by 6 months if the infant is not infected. The serological response after therapy might be slower for infants treated after the neonatal period. Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality. Novel treponemal pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century. It is primarily sexually transmitted but vertical transmission during childbirth is important. It is estimated that there are around 106 million new cases each year worldwide, with a prevalence of 36 million [1]. The highest rates are found in large conurbations and infection tends to be concentrated in core groups. Age the highest rates of infection occur in young people, especially in teenage women and men in their early twenties. Introduction and general description Gonorrhoea results in a number of clinical syndromes including urethritis, cervicitis, epididymoorchitis, pelvic inflammatory syndrome, disseminated gonococcal infection and ophthalmia neonatorum. Pathophysiology Predisposing factors Gonorrhoea has a high infectivity and is easily transmitted before symptoms appear. Socioeconomic and behavioural factors and patterns of sexual mixing affect its spread, and the social network in which an individual is involved will partly determine the risk of infection. The likelihood depends on the preva lence of gonococcal isolates that are likely to disseminate. The gonococci attach to host mucosal cells with the aid of pili, which cover the entire outer cell surface, and outer membrane proteins. They may also be able to multiply intracellularly and exit from the basal surface of the cell [3]. The host mounts an acute inflammatory response that leads to epithelial sloughing, submu cosal microabscesses and purulent discharge. Strains that have the ability to resist the activity of antibodies and complement predis pose to dissemination. Outside the human host the organ ism is delicate and susceptible to drying, but within the body it has a large capability to effect antigenic variation, which helps it evade the host immune response and to develop antimicro bial resistance. These all affect attach ment of the gonococci to cells and phagocytes and results in them being more resistant to the bactericidal effects of human serum. Infection may be asymptomatic and diagnosed as a result of opportunistic testing or contact tracing.

Any thick keratin should be pared off symptoms e coli detrol 4 mg low price, especially in plantar warts [103] medications narcolepsy detrol 4 mg with amex, and the surface dried before freezing begins treatment diarrhea buy discount detrol. In standard treatment treatment bulging disc purchase genuine detrol, the application is continued until a rim of iced tissue (easily seen as a white discoloration) about 1 mm in width develops in the normal skin surrounding the wart symptoms in early pregnancy purchase detrol 2 mg fast delivery. This may require a continuous or pulsed spray for between 5 and 20 s treatment variable purchase detrol canada, depending on the size and thickness of the wart. Longer freezing (over 25 s of continual freeze) is more likely to leave scarring, possibly damage underlying structures and not improve clearance rates [104]. After thawing, a second freeze cycle will improve the cure rate in plantar warts, although the benefit is less marked in hand warts [106]. As well as damaging cells, cryotherapy may lead to clearance by stimulating the development of an immune response [107]. The response to treatment with cryotherapy is comparable or slightly better than that achieved with salicylic acid [75,76]. More frequent treatments may improve responses although will induce more pain, and longer intervals are less effective. If this fails, or when a wart is particularly painful or deep, or both, as may occur over a bony prominence on the foot, more prolonged application, typically up to 30 s, perhaps repeated after thawing, may be used to achieve a greater destructive effect at the cost of significantly greater blistering and pain. The common practice of dipping cotton buds for different patients into a common flask containing the liquid nitrogen may carry a risk of crossinfection. This is unpredictable and surprisingly variable between patients, but in some cases, especially with longer freezing times, it may be severe and persist for many hours or even a few days. Swelling of the treated area and the surrounding skin begins within minutes, and where tissues are lax as in the periorbital area it may be dramatic. Occasionally, damage to underlying tissues may result, for example to a tendon [110] or the nail matrix, and excessive freezing times should be avoided over nerves, for example on the sides of the fingers. Depigmentation may occur, and can be a significant cosmetic disadvantage in patients with darkly pigmented skin. As another destructive method, the infrared coagulator can be used to treat warts. The reported cure rate in a series of 44 warts was 70% [125] which compares favourably with cryotherapy. Excision is usually to be avoided since scarring is inevitable and recurrences of the wart in the scar are frequent. Curettage and cautery/electrocoagulation, usually in combination, may be used for painful or resistant warts, but carry a risk of scarring. Systemic or topical aminolaevulinic acid can be taken up by dividing cells, metabolized to protoporphyrin and then photoactivated to produce a damaging effect on the cell. The treatment may need to be repeated two or three times but can be limited by pain [130]. Dinitrochlorobenzene was the first allergen used to treat cutaneous warts but this chemical is no longer used due to the potential risk of carcinogenesis. The side effect of itching at treatment sites is generally tolerated, but some patients develop dermatitis in other areas or widespread urticaria [149]. The use of squaric acid dibutylester as a contact allergen in such regimens may be equally efficacious and better tolerated [150]. Trials using intralesional Candida antigen to produce a local hypersensitivity reaction suggest that this approach could speed wart resolution in recalcitrant cases [152]. Different interferons have been administered by different routes to patients with refractory warts in various sites. These studies are seldom directly comparable, and the use of interferons in warts is still experimental. The majority of studies have involved patients with refractory genital warts and interferon use has mostly been disappointing. Cutaneous warts on the palms and soles may have been treated with intralesional interferon, using a needleless injector [157]. Results from the use of oral cimetidine in wart treatment in adults have been conflicting. Podophyllin and purified podophyllotoxin act as antimitotics, disrupting the formation of the spindle on which chromosomes align at mitosis. They are used mainly for the treatment of anogenital warts but can also have an effect in cutaneous warts, although penetration into keratinized skin may be poor. They have been used with caution under prolonged occlusion [131] or in a strength of 5% in combination with salicylic acid and cantharidin applied every 2 weeks for up to 10 weeks [132,133]. Podophyllin and Part 3: InfectIons & InfestatIons the carbon dioxide laser has a greater risk of producing scarring but has been used to treat a variety of different forms of wart, both cutaneous and mucosal [117]. It can be effective in eradicating some difficult warts, such as periungual and subungual warts which have been unresponsive to other treatments. Carbon dioxide laser therapy is well tolerated, but can cause significant postoperative pain, hypertrophic scarring and temporary loss of function [117] [120]. Infectious virus can be detected in the plume during carbon dioxide laser use [121], so an operator mask and air extraction system are advised. Laser treatment for other indications has been associated with the spread of facial warts [122,123]. Topical immunomodulation with imiquimod 5% cream is licensed for treatment of genital warts, superficial basal cell carcinoma and actinic keratoses. Cutaneous warts have also responded to imiquimod treatment [135], although poor penetration through the keratinized surface may necessitate twice daily application for up to 24 weeks, or combination with salicylic acid to achieve useful results [136]. The treatment can cause irritation, discomfort and occasionally erosion at the point of application with a small risk of causing vitiligolike depigmentation [142]. In children, cimetidine may produce slightly greater benefit [162,163] and combination treatment with levamisole may enhance the effect [164]. Ranitidine has been assessed in an open study in which 49% of patients with common or plane warts cleared whilst taking 300 mg twice daily [165]. Topically, zinc sulphate as a 10% aqueous solution applied three times daily for 4 weeks in a doubleblind trial, produced a cure rate of 86% for plane warts [168]. Oral retinoids, by reducing epidermal proliferation, can help to debulk warts, although the infection may persist making relapse likely. Acitretin and isotretinoin have been reported to be helpful in cases of extensive and hyperkeratotic warts in immunosuppressed patients [170,171]. Hyperkeratotic warts in otherwise healthy patients can respond to oral retinoid therapy [172,173]. This effect may be temporarily useful, perhaps in relieving pain or disability due to exceptionally hyperkeratotic warts, or in facilitating the use of other treatments. Injections are into the wart itself, confirmed by observing blanching in the lesion, the volume per injected lesion ranging between 0. Injections are very painful and preceding or concurrent local anaesthesia should be considered, especially for sensitive sites such as the fingers and soles [181]. In open studies, cure rates for previously refractory warts are reported to be between 20 and 100% [179,180,182], with some superiority over cryotherapy [183,184]. Trials comparing intralesional bleomycin with placebo have shown a useful effect [177,185]. Local complications include nail loss [186] or dystrophy [187] following periungual injections, Raynaud phenomenon in treated fingers and local pigmentation [188] or urticaria [186]. Flagellate hyperpigmentation, more commonly a feature after systemic administration, has been reported after local injection [189] and this potential risk of systemic absorption is a contraindication for intralesional bleomycin in pregnancy [179]. Implantation of the bleomycin from a surface application using a sterile lancet [190] or the Dermojet [191] may be better tolerated. Side effects, mainly seen with systemic administration, include nephrotoxicity, metabolic acidosis and bone marrow suppression. Local application especially on mucosal surfaces can produce erosion and pain but topical treatment of skin lesions is generally well tolerated [194]. Formal hypnosis, however, was reported to clear warts on the suggested (the more severely affected) side only, in nine of 10 patients who achieved a satisfactory depth of hypnosis, the other side of the body acting as an internal control [199]. Persistent refractory warts disappeared following hypnosis in an uncontrolled study of three immunodeficient children [200]. Incidence and prevalence In countries with highly developed medical services, referral rates of genital warts have greatly increased in the last 50 years. Sex the incidence and prevalence in males is higher than in females with a male: female ratio of 1: 0. The thinner mucosal surface is presumably more susceptible to inoculation of virus than thicker keratinized skin, but in addition lesions are commonest in sites subject to greatest coital friction in both sexes. Human papillomavirus transmission has been most closely studied in the case of anogenital warts. Acquisition most commonly follows sexual contact but it is generally agreed that ano genital warts are not always transmitted sexually. Perianal warts may accompany genital warts, either due to local spread of infection or to direct contact during anal coitus. In prospective studies, approximately twothirds of sexual contacts of patients with genital warts developed lesions themselves within 24 months; infectivity seemed highest early in the course of the disease [207,208]. Occasional nonsexual acquisition of anogenital warts in adults is assumed to be possible. With the lack of largescale prospective studies, the possibility of bias in referral or in reporting should be considered, and there remains insufficient information to offer a reliable estimate of the relative frequency of sexual abuse in such cases. Postnatally, transmission from adults with genital warts may occur nonsexually [220] such as by sharing a bath with an infected adult. A review of reports published between 1976 and 1983 [221] found that, of the total of 21 cases, the probable route of infection was believed to be sexual in 11, prepartum or intrapartum in three, and unknown in seven. In studies of children with anogenital warts assessed for possible sexual abuse, the mode of acquisition was thought to be sexual in no more than 5% [222,223]. Thus, on present incomplete information, both sexual and nonsexual routes are significant in the transmission of childhood anogenital warts [224]. The long and variable incubation period, the possibility of latent or subclinical infection in the source and the problems in eliciting an accurate account of sexual contact from the child and of confirming it from the perpetrator, all make it difficult to decide which applies in an individual case. Where sexual abuse is suspected, the case should be referred to a paediatrician or child abuse specialist. The risk of transmission from mother to child with subsequent development of disease in the child has been estimated to be between 1/80 and 1/1500 [226] but only 57% of cases of laryngeal papilloma in children are diagnosed by 2 years of age [227]. The connective tissue is frequently very oedematous and the capillaries tortuous and increased. The typical anogenital wart is soft, pink, elongated and sometimes filiform or pedunculated. The lesions are usually multiple especially on moist surfaces, and their growth can be enhanced during pregnancy [236], or in the presence of other local infections [237]. The commonest sites, the area of the frenulum, corona and glans in men, and the posterior fourchette in women, correspond to the likely sites of greatest coital friction [236]. Most other lesions are flat, though more conspicuous than plane warts elsewhere, and some of these, generally on nonmucosal surfaces such as the penile shaft, pubic skin, perianal skin and groins, may be sufficiently pigmented to resemble seborrhoeic keratoses. Occasionally, only lesions resembling common warts are seen, in men usually on the penile shaft, and these may be the result of contact with common warts elsewhere on the patient or on the sexual partner [238]. Antiretroviral treatment may lead to worsening of the warts rather than improvement [243]. Childhood cases are believed to result from maternal infection, probably at birth during vaginal delivery. Latent or subclinical infection in the laryngeal mucosa presumably explains recurrences after successful treatment, and might explain adultonset cases, although some of these may be due to sexual transmission [249]. Conjunctival papillomas Human papillomavirus of the lowrisk mucosal type is frequently detected in conjunctival papillomas [251] with rare detection of highrisk types [252]. The development of large protuberant masses, induration, pain or serosanguinous discharge should arouse suspicion of malignant change requiring prompt excision or biopsy and also assessment of immune status. Histologically, differentiation from malignant condylomas may be difficult after treatment with podophyllin or podophyllotoxin due to increased mitotic index.

White piedra is characterized by the presence of soft treatment hyperkalemia purchase 2 mg detrol free shipping, white or light brown nodules symptoms celiac disease order 4 mg detrol mastercard. The infection is more common on the hairs of the beard 5 medications post mi effective detrol 1mg, moustache and genital Otomycosis 32 treatment arthritis cheap detrol. Responses to concentrated topical antifungals treatment plant order detrol in united states online, azoles and allyamines have been reported but are unpredictable symptoms you have diabetes order detrol 1mg on-line. External otitis in general, including the differential diagnosis and management, is considered in Chapter 108. The fungus grows both within and outside the hair shaft, and the hair shaft may be weakened and break off. The nodules are transparent, easily detached from the hair and vary in size from microscopic to 1 mm in diameter. Very occasionally in external otitis, the fungus isolated appears to be playing a pathogenic part, perhaps even a primary one. The species most commonly accepted as pathogens in this situation include Aspergillus niger. Differential diagnosis the presence of pruritus and the distinctive shape of egg cases of pediculi should serve to distinguish pediculosis from piedra, but microscopical examination is desirable. Investigations the nodules of white piedra are in the form of a sheath, which may extend around the hair shaft. There may be extensive growth within the hair, giving rise to characteristic nodular swellings on the hair shaft. Most Trichosporon species are inhibited by cycloheximide, so this antibiotic should be excluded from the culture medium. Colony: the colonies of Trichosporon species develop rapidly and are soft, creamy and wrinkled, and sometimes mucoid [10]. Microscopy: the genus Trichosporon is characterized by the presence of hyphae, arthroconidia and budding cells. These are best observed with a deep cut streak on cornmeal or rice agar supplemented with Tween 80. In advanced cases of true mycotic otitis, an overgrowth of fungal hyphae may produce a mass of white material suggesting damp cotton wool, lodged in the external canal. Clinical variants In severely immunocompromised patients, the external auditory meatus can be extensively eroded by fungal invasion to produce a necrotic form of otitis externa [5]. This form may spread to involve other sites including the middle ear and mastoids. Differential diagnosis the pinna may be the site of several mycotic diseases including chromomycosis [6], sporotrichosis [7] and tinea [4], but such infections usually spare the external auditory meatus. Investigations Interpretation of the relevance of organisms recovered from swabs taken from the ear may be difficult and a light growth of a mould may be of little significance. Rhizopus, Lichtheimia, Mucor or Penicillium, or indeed Aspergillus species, in small amounts mean little, except in immunocompromised patients, where they may be more important. Similarly, a light growth of Candida may reflect colonization or contamination, although this organism can cause external otitis. The criteria for accepting the fungus as having an aetiological role are the absence of any significant bacterial pathogens and the presence of large masses of fungi that may sometimes be seen on examination of the patient. If there is a considerable amount of fungal material in specimens taken for direct examination, this may be adequate evidence. Signs and symptoms present in otomycosis are largely similar to those of otitis due to other aetiological agents, although pruritus and discharge have been shown to be more common in fungalassociated disease in one study [2]. Colony: growing rapidly, the colony initially has a white or cream surface, which becomes black as the conidia are produced. Microscopy: the conidiophores arise at right angles to the supporting hyphae, and have a swollen globose vesicle at their tip, which is completely covered by a layer of supporting cells or metulae. These metulae support a layer of phialides, which produce chains of dark brown, roughwalled phialoconidia. The bottom end of the conidiophore ends in a foot cell inserted in the supporting hypha. From time to time, however, reports appear in the dermatological literature of cases in which species such as those of Aspergillus [1] appear to colonize damaged tissues, become firmly established and perhaps cause secondary tissue destruction. Most authors counsel caution before accepting any sort of pathogenic role for the moulds in these cases. Investigations and management In situations like these, it is important to take repeated scrapings, to use cycloheximidefree media in culture and then to weigh the facts carefully before assuming that the organism is anything more than a contaminant. In many cases, simple correction of local precipitating factors, such as maceration or occlusive dressings, may be all that is needed. Thus defined, the ringworm species are all moulds belonging to three asexual genera: Microsporum, Trichophyton and Epidermophyton. General description Forty years ago, the sexual state of dermatophytes was unknown, and this phase of the life cycle has still not been found for many of the common species. However, in those species where the sexual state has been identified, all the organisms are classified in the single genus Arthroderma in the phylum Ascomycota [3]. A list of synonyms of sexual and asexual names is included for reference (Table 32. However, as sexual states are not routinely seen in the diagnostic laboratory, the name currently given to the asexual anamorph names will be used throughout this section. One routine consists of applying 2% thymol in 70% alcohol during cleansing, followed by 50% metacresyl acetate or olive oil on a pledget of cotton wool left for 24 h. Clotrimazole lotion has been employed with success in both Aspergillus and Candida infections. Bifonazole lotion and cream were effective in the majority of 35 patients included in a longterm study attempting to correlate the bacterial and fungal flora in patients with symptomatic otomycosis [9]. Oral itraconazole has been used in the aggressive invasive form of otitis externa. Miscellaneous superficial mycoses caused by saprophytic moulds the normal skin, especially the scalp and toe clefts, is commonly contaminated with spores or even short lengths of mycelium of saprophytic species. Where the fungal mycelium is pigmented or where distinctive spores are concerned, they may be recognized in direct examination of skin scrapings. Usually, such species are present in small amounts, and may without difficulty be dismissed as contaminants that have impacted on the skin, in the same way Asexual state Microsporum canis Microsporum fulvum Microsporum gypseum Microsporum gypseum Microsporum nanum Microsporum persicolor Trichophyton mentagrophytes Trichophyton mentagrophytes Trichophyton simii Sexual state Arthroderma otae Arthroderma fulvum Arthroderma incurvatum Arthroderma gypseum Arthroderma obtusum Arthroderma persicolor Arthroderma benhamiae Arthroderma vanbreuseghemii Arthroderma simii Dermatophytosis 32. The taxonomy of dermatophytes is an ever changing area and the use of molecular techniques to examine the relatedness of species has led to many controversies and conflicts in the literature. However, this is a matter of conflict and debate among taxonomists in this area [5,6], and this synonymy was later formally rejected [7]. Detailed discussions on the molecular taxonomy of dermatophytes are beyond the scope of this volume and interested readers are referred to a review on this subject [8]. The three asexual dermatophyte genera are distinguished by the morphology of the large, multicellular macroconidia that are produced [9]. Those of Trichophyton species are thin walled, smooth and may be cylindrical, fusiform or clavate in shape, with up to 12 transverse septa. In Epidermophyton, the macroconidium is clavate, broadened and rounded at its distal pole, thin walled and has up to five septa; the conidia are smooth when first formed, but as the colony ages, discrete wall thickenings may be observed. Apart from the mycological classification of dermatophytes, it has been traditional for clinical and epidemiological reasons to group dermatophytes that infect humans according to their ecological niche: geophilic species originating in the soil (Table 32. Species Epidermophyton floccosum Microsporum audouinii Isolates previously called M. Species that are clearly geophilic may contaminate or infect the coats of animals, especially small rodents, and may thus infect humans through an intermediate animal host. Similarly, animal species may shed infective material on to the soil and, although incapable of multiplying there, fungal elements may survive long enough to be isolated in a soil survey [10]. In the case of species affecting farm animals, their environment including cow sheds and fences may be contaminated by desquamated keratinocytes or hair containing fungal spores, just as the floors around swimming baths, school classrooms and the air of hospital clinics may be contaminated by anthropophilic species [10]. The distribution of the zoophilic species reflects that of the major animal hosts. Those geographically limited include Microsporum canis (including strains previously called M. Many of the anthropophilic species are also geographically limited and the classic endemic distributions are indicated in Table 32. However, to some degree these must reflect the distribution of diagnostic facilities, and data for some areas are slight or outdated. Also, the anthropophilic dermatophytes are spread by movements of individuals and groups. The European infections have not been found among immigrants from the endemic areas alone, but also in children born in Europe of African immigrants and, more rarely, among the endemic European population. It must also be appreciated that these distributions are not static, and the range of species in some areas may change dramatically and quickly. For instance, in one central London laboratory during the period between 1980 and 1990, the most common isolate from tinea capitis was the zoophilic organism M. From the evolutionary point of view, it is likely that the anthropophilic species represent the end of a line, starting with nonpathogenic, keratinophilic soil species, existing as saprophytes on keratinous debris, passing through the geophilic dermatophytes and the zoophilic species. Virtually all the nonpathogenic, keratinophilic species and geophilic dermatophytes have demonstrable sexual states, as do a few of the zoophilic group, particularly those infecting animals living in burrows or dens and thus associated with soil. It has been suggested that this transition from sexual to asexual life cycles led to an unprecedented level of adaptive radiation among the anthropophilic dermatophytes, resulting in a large number of species and variants. Other factors that may have contributed to the adaptive radiation on humans include the separation of the human skin into distinct areas differing in the distribution of sebaceous glands and hairs, resulting in a marked affinity for particular body sites among the anthropophiles, which is not seen in zoophiles. Basic biology Characteristically, zoophilic species tend to produce highly inflammatory reactions in humans and this may lead to a spontaneous cure. An important characteristic of the dermatophytes as parasites is their restriction to dead keratinized tissue. Although the inflammatory responses of ringworm infection involve the dermis and the Malpighian stratum of the epidermis, the fungus itself is found growing only within the stratum corneum of the epidermis, within and around the fully keratinized hair shaft, and in the nail plate and keratinized nail bed. Within these keratinized tissues, the fungus exists only as mycelium and arthroconidia. In this parasitic phase of fungal growth, there are no micro or macroconidia and no specialized vegetative structures, such as spiral or pectinate hyphae. For these reasons, precise identification of the species of an infecting dermatophyte is generally impossible on direct microscopy of the skin or nail. In dermatophyte infections involving hair, the fungus invades the follicle from the adjacent stratum corneum and follows one of several precise patterns of growth. It then grows downwards within the hair towards the bulb, until the zone of incomplete keratinization is reached. An equilibrium is established, the fungal mycelium invading a new, fully keratinized hair shaft at the same rate as it is formed, but never growing down into the incompletely keratinized tissue. Further up the shaft, hyphae from the existing mycelium grow outwards from inside the hair and proliferate on its surface. These secondary, extrapilary hyphae are tortuous; they fragment into small arthroconidia, which rapidly round up to become spherical structures, and are seen as a packed mosaic of spores coating the surface of the hair. The hyphae within the hair are fewer in number than in other endothrix infections and do not break up into a mass of arthroconidia but run intact through the hair, forming tunnels within its structure. When mounted in potassium hydroxide, these tunnels formed originally around the hyphae, which subsequently degenerate, create the characteristic air spaces seen. While in favus the infected hair commonly grows to normal lengths, in endothrix infections where arthroconidia are formed the hair shaft, being severely weakened, breaks at the skin surface. In smallspored ectothrix infections the shaft tends to fracture a few millimetres above the surface. All these parasitic patterns are very different from the mode of growth of dermatophytes on hair in vitro [3]. Conical pits are then formed perpendicular to the surface of the hair as penetration of the keratinized hair cortex occurs. Intrapilary growth follows along the hair shaft in both directions, and micro and macroconidia may be produced. Invasion of the epidermis Invasion of the epidermis by dermatophytes follows a common pattern, starting with adherence between arthroconidia and keratinocytes, followed by penetration through and between cells and the development of a host response. On the stratum corneum, the first phase of dermatophyte invasion involves the adherence of infectious arthroconidia to keratinocytes. In vitro, this process is completed after about 2 h of contact, at which stage germination and penetration of the keratinocyte occurs [4]. Different dermatophytes show similar kinetics, which are also unaffected by the source of the keratinocytes. The germination of arthroconidia and hyphal prolongation that follows adherence proceeds radially, and in vitro there is evidence of the indentation of keratinocyte layers beneath the growing hyphae, possibly resulting from enzymic action [5]. Evidence for this ranges from the ability of many dermatophytes to invade hair and nail in vitro to the demonstration of genetically regulated production of proteases with keratin specificity. In vitro, nonkeratin substances extracted from keratinized tissues will support the growth of dermatophytes [6].

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