By N. Lester. Austin Peay State University.

The corneocytes are joined together by the lipid and glycoprotein of the intercel- lular cement material and by special connecting structures known as desmosomes quality 100 mg doxycycline. On limb and trunk skin doxycycline 200mg on line, the stratum corneum is some 15–20 cells thick and, as each corneocyte is about 1 m thick, it is about 15–20 m thick in absolute terms. The stratum corneum prevents water loss and when it is deranged, as, for example, in psoriasis or eczema, water loss is greatly increased so that severe dehy- dration can occur if enough skin is affected. It has been estimated that a patient with erythrodermic psoriasis may lose 6 L of water per day through the disordered stratum corneum, as opposed to 0. The stratum corneum also acts as a barrier to the penetration of chemical agents with which the skin comes into contact. It prevents systemic poisoning from skin contact, although it must be realized that it is not a complete barrier and percutaneous penetration of most agents does occur at a very slow rate. Those responsible for formulating drugs in topical formulations are well aware of this rate-limiting property for percutaneous penetration of the stratum corneum and try to find agents that accelerate the movement of drugs into the skin. The barrier properties are, of course, also of vital importance in the prevention of microbial life invading the skin – once again the barrier properties are not perfect, as the occasional pathogen gains entry via hair follicles or small cracks and fissures and causes infection. The structure is very extensible and compliant in health, permitting movement of the hands and feet, and is actually quite tough, so that it provides a degree of mechanical protection against minor penetrative injury. This cellular structure is some three to five cell layers thick – on average, 35–50 m thick in absolute terms (Fig. Not unexpectedly, the epidermis is about two to three times thicker on the hands and feet – particularly the palms and soles. The epidermis is indented by finger-like projections from the dermis known as the dermal papillae (Fig. The cells of the epidermis are mainly keratinocytes containing keratin tonofila- ments, which are born in the basal generative compartment and ascend through the Malpighian layer to the granular cell layer. They are joined to neighbouring keratinocytes by specialized junctions known as desmosomes. These are visible as ‘prickles’ in formalin-fixed sections but as alternating light and dark bands on electron microscopy. In the granular layer, they transform from a plump oval or rectangular shape to a more flattened profile and lose their nucleus and cytoplasmic 4 Skin structure and function (a) (b) Figure 1. The Basal Lamina Tonofilaments Sub basal Attachment plaque dense plaque Plasma membrane Lamina lucida Anchoring filaments Basal lamina Anchoring fibril Dermal microfibril bundle Figure 1. In addition, they develop basophilic granules containing a histidine- rich protein known as filaggrin and minute lipid-containing, membrane-bound structures known as membrane-coating granules or lamellar bodies. These alterations are part of the process of keratinization during which the keratinocytes differentiate into tough, disc-shaped corneocytes. Other changes include reduction in water content from 70 per cent in the keratinocytes to the stratum corneum’s 30 per cent, and the laying down of a chemically resistant, cross-linked protein band at the periphery of the corneocyte. Of major importance to the barrier function of the stratum corneum is the inter- cellular lipid which, unlike the phospholipid of the epidermis below, is mainly polar ceramide and derives from the minute lamellar bodies of the granular cell layer. It takes about 28 days for a new keratinocyte to ascend through the epidermis and stratum corneum and desquamate off at the skin surface. This process is greatly accelerated in some inflammatory skin disorders – notably psoriasis. Melanocytes account for 5–10 per cent of cells in the basal layer of the epidermis. Melanin is a polymer, synthesized from the amino acid tyrosine with the help of a copper-containing enzyme, tyrosinase. Interestingly, the number of melanocytes in skin is the same regardless of the degree of racial pigmentation – it is the rate of pigmentation that differs. Langerhans cells Langerhans cells are also dendritic cells, but are found within the body of the epi- dermis in the Malpighian layer rather than in the basal layer. They derive from the reticuloendothelial system and have the function of picking up ‘foreign’ material and presenting it to lymphocytes in the early stages of a delayed hypersensitivity reaction. It is composed primarily of tough, fibrous collagen and a network of fibres of elastic tissue, as well as containing the vascular channels and nerve fibres of skin (Fig. Between the fibres of collagen is a matrix composed mainly of proteoglycan in which are scattered the fibro- blasts that synthesize all the dermal components. Collagen bundles are composed of 6 Skin structure and function Collagen fibres Tropocollagen ~240nm Collagen fibre or fibril Fibroblast Bundle of collagen fibres in cross section 64nm Periodicity in Diameter of individual long section of fibre fibres varies from 20 to 120nm. Elastic tissue has two Elastic fibres components: • Microfibrils The ratio of • Amorphous substance fibrils to amorphous The amorphous substance consists substance of molecules of elastin cross linked varies. The dermal vasculature There are no blood vessels in the epidermis and the necessary oxygen and nutrients diffuse from the capillaries in the dermal papillae. Nerve structures Recently, very fine nerve fibres have been identified in the epidermis, but most of the fibres run alongside the blood vessels in the dermal papillae and deeper in the 7 An introduction to skin and skin disease Figure 1. There are several types of specialized sensory receptor in the upper dermis that detect particular sensations (Fig. Hair follicles Hair follicles are arranged all over the skin surface apart from the palms and soles, the genital mucosa and the vermilion of the lips. The different phases of our asynchronous hair growth occur independently in individual follicles but are timed to occur together in synchronous hair growth, accounting for the phenom- enon of moulting in small, furry mammals.

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Multi-drug resistant strains have been a large number of organisms is usually necessary reported in Asia cheap 200mg doxycycline visa, the Middle East buy cheap doxycycline 200mg on line, and Latin America. The organisms are absorbed from the gut and Manifestations transported via the blood stream to the liver and • In the early stages fever, severe headache, spleen. They are released into the blood after 10 to constipation and a dry cough may be present. The • The fever rises in a “step ladder” pattern for 4 or 5 organisms localise in the lymphoid tissue of the days. This • Abdominal tenderness and an enlarged liver or is the main cause of death from typhoid fever. The • If untreated, complications can occur during the incubation period is from 10 to 21 days. Most patients who have typhoid will excrete • Other complications may affect any patient organisms at some stage of their illness. About because of the occurrence of septicaemia during 10% who have typhoid fever excrete the organisms the first week. These may include cholecystitis, for approximately three months after the acute stage pneumonia, myocarditis, arthritis, osteomyelitis of the illness and 2 to 5% of untreated patients and meningitis. Incidence of becoming • Bone and joint infection is seen, especially in a carrier increases with age, especially in females. Epidemiological summary Age groups affected The organism responsible for typhoid fever was Typhoid can affect any age. Typhoid fever affects Case-fatality rates of 10% can be reduced to less 17 million people in the world annually, with than 1% with appropriate antibiotic therapy. Module 3 Page 77 Diagnosis Treatment of carriers: this can often be very Blood culture is the most important method for difficult to implement, but spread through carriers diagnosis. Isolation of the organism from the stool is unusual if good personal hygiene is practised and is more common in the second and third weeks of stools are disposed of hygienically. In some cases, isolation of the bacteria in the urine can be used as a diagnostic method. Selective immunization of groups: during an epidemic in an endemic country, selective Methods of treatment immunization of groups such as school children, Four different antibiotics are often used for institutionalized people and healthcare workers is treatment: Ciprofloxacin, Co-trimoxazole, of great benefit. Effective treatment does not always prevent complications, Immunization against typhoid the disease recurring or the patient becoming a There are three types of typhoid vaccine: carrier. A chronic carrier may be treated for four weeks with aminoquinalones and in some cases it • Monovalent whole cell typhoid vaccine contains may be necessary to perform a cholecystectomy, in excess of 1000 million S. Two doses, given four to Prevention of spread is dependent upon: six weeks apart, give protection for three years, but • Clean water supply: protection and chlorination side effects include a painful reaction at the of public water supplies is necessary. It provides equally effective protection as the whole cell vaccine but with fewer Page 78 Module 3 febrile side effects, although it can cause irritation general examination for complications; at the vaccine site. Length Rehabilitation of protection may be less and vaccination may need Recovery may be complete after treatment, but may repeating after one year. The vaccine is unstable at also be delayed with recurrence of the symptoms room temperature and must be kept refrigerated. Recurrence is more It should be emphasized that whilst these vaccines likely to occur after inadequate treatment. Consequently strict food, water and personal Role of primary health care team hygiene protection continue to be of great • Education regarding food, water and personal importance. Blood • Awareness of the risks and management of patient cultures can provide early confirmation; the with carrier status organism can then be tested for antibiotic sensitivity. Stool and urine culture may also be Role of health education and health promotion performed from one week following confirmation • Heighten public awareness of the disease and of the disease. Water and food samples from its prevention suspected sources also need to be tested. The virus most commonly invades Paratyphoid usually has a shorter incubation period, the gastrointestinal tract and a viraemic illness may with diarrhoea from the onset, a more abundant develop. In some cases the virus invades and rash and less commonly develops intestinal destroys the anterior horn cells of the spinal cord. In the most severe cases, the virus attacks the motor neurons of the brainstem, causing difficulty in breathing, swallowing and speaking. Modes of transmission • The faecal-oral route, particularly in areas where there is poor food and water hygiene. Communicability Cases are most infectious from 7–10 days before and after onset of the illness, although the virus may be shed in the faeces for up to six weeks or even longer. Epidemiological summary It is thought that poliomyelitis first occurred nearly 6000 years ago in the time of the ancient Egyptians. Evidence for this theory lies in the withered and deformed limbs of some Egyptian mummies. Since the development of the polio vaccine in the mid- 1950s, cases of poliomyelitis have diminished dramatically. The disease was brought under control and practically eliminated as a public health problem in industrialized countries. Today the disease has been eradicated from large parts of the world; the key remaining reservoirs of Page 80 Module 3 virus transmission • The level of damage to the spinal cord determines are in South Asia the muscles affected.

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Endemic foci exist in the mountainous regions of Mexico discount 100 mg doxycycline otc, in Central and South America cheap doxycycline 200 mg with mastercard, in central and eastern Africa and numerous countries of Asia. Reservoir—Humans are the reservoir and are responsible for maintaining the infection during interepidemic periods. Although not a major source of human disease, sporadic cases may be associated with flying squirrels. Mode of transmission—The body louse, Pediculus humanus corporis, is infected by feeding on the blood of a patient with acute typhus fever. Patients with Brill-Zinsser disease can infect lice and may serve as foci for new outbreaks in louse-infested communities. Infected lice excrete rickettsiae in their feces and usually defecate at the time of feeding. People are infected by rubbing feces or crushed lice into the bite or into superficial abrasions. Transmission from the flying squirrel is presumed to be through the bite of the squirrel flea, but this has not been documented. Period of communicability—The disease is not directly transmit- ted from person to person. Patients are infective for lice during the febrile illness and possibly for 2–3 days after the temperature returns to normal. Infected lice pass rickettsiae in their feces within 2–6 days after the blood-meal; they are infective earlier if crushed. The louse invariably dies within 2 weeks after infection; rickettsiae may remain viable in the dead louse for weeks. Preventive measures: 1) Apply an effective residual insecticide powder at appropriate intervals by hand or power blower to clothes and persons of populations living under conditions favoring louse infesta- tion. Lice tend to leave abnormally hot or cold bodies in search of a normothermic clothed body. When faced with a seriously ill patient with possible typhus, suitable treatment should be started without waiting for laboratory confirmation. Epidemic measures: The best measure for rapid control of typhus is application of an insecticide with residual effect to all contacts. Where louse infestation is known to be widespread, systematic application of residual insecticide to all people in the community is indicated. In epidemics, individuals may protect themselves by wearing silk or plastic clothing tightly fastened around wrists, ankles and neck, and impregnating clothes with repellents or permethrin. Disaster implications: Typhus can be expected to be a significant problem in louse-infested populations in endemic areas if social upheavals and crowding occur. The initial reference treatment of any suspected case is a single dose of 200 mg of doxycycline. Identification—A rickettsial disease whose course resembles that of louse-borne typhus, but is milder. Absence of louse infestation, geographic and seasonal distribution and sporadic occurrence of the disease help to differentiate it from louse-borne typhus. Infection is maintained in nature by a rat-flea-rat cycle where rats are the reservoir (commonly Rattus rattus and R. A closely related organism, Rickettsia felis, has been found to pass from cat to cat flea to opossum or other animals in North America, Europe and Africa. Mode of transmission—Infective rat fleas (usually Xenopsylla cheopis) defecate rickettsiae while sucking blood, this contaminates the bite site and other fresh skin wounds. Once infected, fleas remain so for life (up to 1 year) and transfer it to their progeny. Preventive measures: 1) To avoid increased exposure of humans, wait until flea populations have first been reduced by insecticides before instituting rodent control measures (see Plague, 9A2-9A3, 9B6). Control of patient, contacts and the immediate environment: 1) Report to local health authority: Case report obligatory in most countries, Class 2 (see Reporting). Epidemic measures: In endemic areas with numerous cases, use of a residual insecticide effective against rat or cat fleas will reduce the flea index and the incidence of infection in humans. Disaster implications: Cases can be expected when people, rats and fleas are forced to coexist in close proximity, but murine typhus has not been a major contributor to disease rates in such situations. Identification—A rickettsial disease often characterized by a pri- mary “punched out” skin ulcer (eschar) corresponding to the site of attachment of an infected mite. An acute febrile onset follows within several days, along with headache, profuse sweating, conjunctival injec- tion and lymphadenopathy. Late in the first week of fever, a dull red maculopapular eruption appears on the trunk, extends to the extremities and disappears in a few days. The case-fatality rate in untreated cases varies from 1% to 60%, according to area, strain of infectious agent and previous exposure to disease; it is consistently higher among older people. Definitive diagnosis is made by isolation of the infectious agent by inoculating the patient’s blood into mice.

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