By P. Saturas. University of Arizona.

The only exception to this is where there is a sig­ more common in women than men buy tadacip 20 mg visa erectile dysfunction protocol amino acids. Extragenital lesions nificant vaginal prolapse order tadacip 20 mg free shipping erectile dysfunction injection, where the epithelium becomes may be seen in about 10% of women with genital involve­ keratinized and lichen sclerosus can then develop on this ment purchase 20mg tadacip with mastercard erectile dysfunction blood flow. Aetiology The aetiology remains unclear but it is thought that it is mediated by a lymphocyte reaction tadacip 20mg on-line impotence quoad hoc. Immunohistochemical alterations of the epidermis and dermis support an auto­ immune cause and circulating IgG antibodies to extracel­ lular matrix proteins have been demonstrated discount 20 mg tadacip visa impotence tumblr. There is an association in both the patient and their first‐degree relatives with other autoimmune diseases buy 20 mg tadacip amex erectile dysfunction medication ratings, particularly thyroid disorders. Flat showing rubbery oedema of labia minora and clitoral hood and white lesions which can coalesce into plaques. This may present as a small persistent erosion or ulcer, a hyperkeratotic area or fleshy friable papule or nodule. Here the squamous cell carcinoma presents as a fleshy Treatment nodule, but persistent erosion should also prompt biopsy. Ongoing treatment may be required by some patients to Surgery is only required to treat the scarring complications 800 Benign Gynaecological Disease or if there is neoplastic or pre‐neoplastic change. Topical calcineurin inhibitors are increasingly popular but should not be used first line as there are concerns about their long‐term safety in relation to the development of malignancy. In those with resistant symptoms, it is important to exclude an allergic contact dermatitis to treatment, irri­ tant dermatitis due to urinary incontinence, or an addi­ tional problem such as herpes simplex or candidiasis. A proportion of patients will develop vulvodynia after their lichen sclerosus is well controlled. Treatment must be targeted at this rather than increasing the use of topical steroids. These may occur in isolation without the presence of dis­ ● Any resistant areas, ulcers or hyperkeratotic lesiors ease at other sites. The char­ the vulva, vagina and gingival margins [7], with specific acteristic cutaneous lesions are small purplish papules, genetic associations. The lacrimal duct, external audi­ which may exhibit a fine lace‐like network over their sur­ tory meatus and oesophagus can also be involved and face known as Wickham’s striae. These can also be seen disease at these sites needs a multidisciplinary approach on mucosal lesions. The vulval lesions mainly affect the inner labia minora The nails can show pterygium formation and scalp and vestibule where erythema and erosions occur lesions can result in a scarring alopecia. A lacy white edge is seen and this is the Histology shows irregular acanthosis with a saw‐ best site for a confirmatory biopsy. There toothed pattern, basal cell degeneration and a dense may be marked scarring with significant architectural band‐like dermal infiltrate of lymphocytes. There is change, which can be impossible to differentiate from often pigmentary incontinence, which is responsible for lichen sclerosus in some cases. Symptomatically the the marked hyperpigmentation sometimes seen clini­ condition is itchy and painful and dyspareunia is a com­ cally. If there is vaginal involvement, there may be a blood‐stained discharge and episodes of post‐coital Aetiology bleeding. It is important to recognize vaginal disease as The cause is unknown but it is likely that it is a T‐lym­ scarring at this site can result in complete vaginal steno­ phocyte‐mediated inflammatory response to some form sis. They are violaceous in colour and are usually also found on the inner wrist and elsewhere. Wickham’s Hypertrophic lesions are less common and mainly striae can also be seen associated with the lesions. They can become Flexural hyperpigmentation can be significant even ulcerated and painful. Vulval eczema is often over‐diagnosed and there is a significant overlap with vulval psoriasis, which is much Management more common. For vaginal disease, some of the greasy scale and particularly affect the naso‐labial folds, foam preparations used in inflammatory bowel disease eyebrows, forehead, scalp and behind the ears. This genital skin may be involved together with other flexural is inserted via the applicator into the vagina at night. There is some evidence for the use of the topical cal­ It is often very difficult to distinguish seborrhoeic cineurin modulators tacrolimus and pimecrolimus in the eczema from flexural psoriasis. There are small case series that support other sites may help and the histology may be similar. It is therefore recommended that they are not used as first‐ line treatment but for short periods in those who do not Irritant eczema respond to potent topical steroids. They are not tolerated The anogenital skin is very susceptible to an irritant well on the anogenital skin, which also limits their use. It is a particular problem in those suf­ Lichen planus fering from urinary or faecal incontinence. It is a response to chronic scratching and rubbing of the skin Eczema and is usually seen on a background of eczema or psoria­ The terms ‘eczema’ and ‘dermatitis’ are used synonymously sis. It isolated area of lichenification without an obvious is characterized histologically by spongiosis where the background dermatitis. The thickened plaques may be Benign Diseases of the Vulva 803 the disease may be triggered by streptococcal infection and trauma (Koebner phenomenon). Psoriasis may also be exacerbated by some drugs, for example beta‐blockers, lithium and chloroquine. Histology shows marked epidermal thickening (acan­ thosis) with deep epidermal ridges projecting into the dermis. There is little scaling because of the moist occluded environment of the anogenital skin. The lesions present on the inner and outer aspects of labia majora as well‐demarcated erythema or salmon‐pink patches that are usually symmetrical. A potent topical steroid applied on a reducing regimen over a 3‐month period can be very helpful and in many cases will resolve the problem. However, in others, it is considered to be a sensory problem and treatment needs to be directed towards breaking the itch–scratch cycle. Management of vulval eczema The management of all eczematous processes is similar. A topical steroid, combined with an antimicrobial if appropriate, can be used once daily ini­. Gauze is soaked in the solution and applied to the affected areas for 15 min once or twice a day. Patients with lichen simplex may require a potent topical steroid to gain control of their symptoms. The frequency of application can slowly be reduced as the lichenification resolves. Psoriasis Psoriasis is one of the commonest skin conditions, affect­ ing about 2% of the population in some form. The char­ acteristic lesions are silvery white scaly plaques on the extensor aspects of the limbs, but generalized disease may occur with scalp and nail involvement. Topical antibiotics can be used in mild disease together The use of an emollient as a soap substitute is helpful. The with other measures such as stopping smoking and traditional treatments for psoriasis (e. In moderate to severe disease, long‐ calcipotriol) are too irritant to be used in the flexures and term oral tetracyclines are the first‐line treatment. Oral therefore a mild to moderately potent topical steroid is clindamycin has been used in some cases with success. This can be applied once daily and then reduced in Second‐line treatments include surgery, anti‐androgen frequency to be used as needed. Oral therapy with methotrexate, cyclosporin and acitretin can be used and the new biological therapies Bullous diseases may be considered in very extensive, resistant cases. Reiter’s disease is an inflammatory response to an Genetic causes enteric or lower genital tract infection, with arthritis, uveitis and skin lesions that are very similar to those of Epidermolysis bullosa psoriasis. The vulva may be affected with a circinate Epidermolysis bullosa is used to describe a group of ulcerative vulvitis similar to the balanitis that commonly inherited conditions (dominant or recessive) character­ occurs in men with this syndrome. These children must be cared for in specialist centres with access to expert nursing care. Hidradenitis suppurativa Hidradenitis suppurativa is an inflammatory disorder Benign familial chronic pemphigus affecting areas where apocrine glands are present. The (Hailey–Hailey disease) basic pathology is not in the gland itself but in the follicu­ This is rare autosomal dominant condition where moist lar epithelium, where an infundibular inflammation, red plaques in the flexures and genital areas develop in possibly triggered by antimicrobial peptides produced the second to fourth decades.

While overtreatment of the epidermis is less common with devices that have built-in cooling mechanisms tadacip 20 mg on-line erectile dysfunction doctors in brooklyn, it can still occur buy tadacip 20mg with amex erectile dysfunction caused by high cholesterol. Prompt application of a wrapped ice pack to areas suspected of overtreatment at the time of treatment that are intensely erythematous and painful may reduce the area of injury purchase tadacip 20 mg erectile dysfunction reasons. Blisters and crusting are managed with application of an occlusive ointment order 20 mg tadacip overnight delivery erectile dysfunction symptoms treatment, like Aquaphor™ or bacitracin cheap tadacip 20 mg with amex impotence age 60, and covered with a gauze dressing and tape order 20mg tadacip otc erectile dysfunction drugs from himalaya. Patients are monitored over the next few weeks for formation of bullae, intense erythema, induration, and scarring. It is associated with aggressive treatment, particularly in areas predisposed to scarring such as the sternum, or with treatments complicated by burns and infection. In addition, recent use of isotretinoin, previous radiation therapy in the treatment area, and a history of keloid formation are also risk factors for hypertrophic scarring. Interventions for persistent intense erythema to reduce the risk of scarring and management of scarring are discussed in Chapter 6, Scarring section. In2 addition, intervals that are too short between treatments do not allow adequate time for hairs to return to the anagen phase and can render laser treatments ineffective. Hair reduction adjacent to the treatment area is possible as hair follicles grow at angles to the skin. It is advisable to avoid treating near the eyebrows as these hairs do grow at an angle and unwanted hair reduction can occur. One study found that immediate application of ice around the treatment area and two passes of the laser in the treatment area reduced the risk of paradoxical hair growth. Once identified, these patients may be pretreated with an antihistamine 1 hour prior to procedure to prevent urticaria formation. Ocular injury from laser light in the eye can be avoided by wearing appropriate laser- safe eyewear at all times during treatment, always directing the laser tip away from the eye and treating outside of the eye orbit. Extremely rare and idiosyncratic complications include bruising, erythema ab igne that is a reticular erythematous rash related to heat exposure, and livedo reticularis that is a vascular condition associated with mottled skin discoloration of the legs or arms exacerbated by heat. Hirsute pediatric patients may be treated with parental consent after medical evaluation for hirsutism. Pain management is important with this population and age appropriate analgesics and dosing is necessary. Axillae are a preferred area to start with as they are flat, minimally sun exposed, and usually have coarse hair. This works by coupling a vacuum chamber to the laser tip which generates negative pressure to flatten skin against the tip thereby reducing discomfort. One such device, Tria™ by Tria Beauty, is a diode (810 nm) that uses a very long pulse width (400 ms) with low fluences (7–20 J/cm ). There is currently no data indicating that permanent reduction can be2 achieved with these devices and they will likely serve as a temporary hair reduction method. The cost for treatments are typically based on the size of the area and can vary widely based on geographic region. A series of 6–8 treatments may be offered to help patients stay on schedule with their treatment intervals and achieve optimal results. The most common benign pigmented lesions associated with photoaging are ephelides (freckles), solar lentigines (sun spots), and mottled pigmentation. This chapter reviews laser principles as they relate to treatment of benign pigmented lesions* and conditions seen in photoaged skin and provides a step-by-step approach to treatment. Anatomy Solar lentigines, also referred to as liver spots and sun spots, are one of the most common benign pigmented lesions seen in photoaged skin. Ephelides (freckles) are similar to lentigines but smaller; they darken in summer and lighten in winter. Photodamaged skin often demonstrates mottled pigmentation, with areas of mixed hypopigmentation and hyperpigmentation. Some patients with photoaging have chronically hyperpigmented skin, referred to as actinic bronzing. Melasma presents as hyperpigmented reticular patches and brown macules on the face, typically involving the cheeks, upper lip, forehead, and chin (s. It is frequently observed following a change in female hormonal status such as during pregnancy (chloasma) and in response to oral contraceptives. Poikiloderma of Civatte presents as erythematous and/or brown discoloration on the chest, lateral neck and cheeks. Pigmentary changes in photoaged skin are due to dysregulation of melanin synthesis and deposition in skin. This results in regions excess with melanin evident as hyperpigmentation such as freckles and lengtigines, and regions with melanin deficiency evident as hypopigmentation. Pigmented lesions can be classified based on depth of melanin accumulation in the skin as epidermal, dermal, or mixed epidermal and dermal. When illuminated with a Wood’s lamp epidermal pigmentation appears darker with more contrast against the background skin, while dermal pigmentation has less contrast. Laser Principles Laser treatment of benign pigmented lesions is based on the principle of photothermolysis. There are two main categories of lasers used to treat pigmented lesions, pigment specific lasers that target the melanin chromophore in pigmented lesions, and skin resurfacing lasers that target the water chromophore in dermal tissue. They use melanin as the target chromophore, which preferentially absorbs light between 600 and 1200 nm. Melanosomes are very small in size (approximately 1 μm) and respond well to these extremely short pulse widths. When a lesion such as a lentigo is irradiated with a pigment specific laser, melanin within the melanosome absorbs energy and is heated and melanosome- containing cells (i. Skin resurfacing lasers use water as the target chromophore, which significantly absorbs light above 1200 nm. These lasers are used primarily for collagen remodeling effects to treat wrinkles and scars, but can also be used to treat pigmented lesions. Epidermal and dermal tissue is removed and pigmented lesions are removed nonspecifically along with this tissue. Nonablative skin resurfacing lasers (fractional) that treat pigmented lesions include 1410, 1440, 1540, 1550, and 1927 nm. Through a process referred to as fractional photothermolysis, these lasers heat and coagulate a portion of the skin in microscopic columns, called microthermal zones. Melanin in the treated microthermal zones is extruded from the epidermis along with other epidermal and dermal debris, thereby reducing unwanted pigmentation. The depth of penetration for these lasers is affected by their water-absorption capabilities, where wavelengths that are highly absorbed by water penetrate superficially and shorter wavelengths with lower water absorption penetrate more deeply. Consequently, 1927 nm targets more superficial lesions and is effective for treatment of epidermal pigmented lesions such as lentigines and ephelides, whereas 1550 nm penetrates deeper to the dermis and is more effective for dermal pigmented lesions such as melasma. Ablative skin resurfacing lasers (both fractional and nonfractional) include 2790, 2940, and 10600 nm. Ablative skin resurfacing lasers are primarily used for treatment of wrinkles and scars, but ablation of epidermal and dermal tissue also removes pigmented lesions. Laser Parameters for Treatment of Pigmented Lesions By adjusting laser parameters of wavelength, fluence, pulse width, and spot size, maximal efficacy and safety can be achieved when treating benign pigmented lesions (also see Introduction and Foundation Concepts, Laser Parameters section). The following discussion focuses on parameters used with pigment specific lasers, discussion of parameters used with skin-resurfacing lasers can be found in the chapters on nonablative and ablative lasers for wrinkle reduction (Chapters 5 and 6 respectively). Short wavelengths penetrate superficially due to high scatter of the laser beam and longer wavelengths penetrate deeper. Shorter wavelengths are more effective for epidermal pigmented lesions and longer wavelengths are more effective for dermal pigmentation and are safer on darker skin types. High fluences are used when less target chromophore is present either due to sparse lesions or faintly colored lesions. Lower fluences are used when more target chromophore is present either due to a high density of pigmented lesions or intensely colored lesions. Short pulse widths are used when less target chromophore is present either due to sparse lesions or faintly colored lesions. Longer pulse widths are used when more target chromophore is present either due to a high density of pigmented lesions or intensely colored lesions. In addition, longer pulse widths penetrate deeper into the skin, making them safer on the epidermis and preferable for treatment of dark skin types.

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Motor deficit may range from should be in strict isolation until follow-up cultures are minor proximal weakness to complete paralysis tadacip 20mg lowest price erectile dysfunction treatment houston tx. Other complications include otitis media and respiratory The local health department must be notified discount tadacip 20mg with amex erectile dysfunction premature ejaculation treatment. Close contacts should have cultures performed and be administered prophylactic antibiotics discount tadacip 20mg with mastercard erectile dysfunction protocol video. All contacts without diagnosis full primary immunization and a booster within the preceding 5 years should receive diphtheria toxoid cheap tadacip 20mg with visa erectile dysfunction hand pump. The specimen should be collected immediately after clinical Antibiotic therapy is not a substitute for antitoxin diagnosis with the swab from the inflamed tissue and one therapy purchase tadacip 20mg online erectile dysfunction trials. Some patients with cutaneous diphtheria have sent for staining and the other for the culture tadacip 20mg online best erectile dysfunction drug review. Elimination of the organism from the nose and throat and any other mucocutaneous should be documented by negative results of at least lesion. A portion of membrane should be removed for two successive cultures of specimens from the nose and culture. Treatment with erythromycin is repeated if either to accurately identify the organism and subsequently culture yields C. Alert the laboratory to the suspicion of diphtheria Prevention because isolation of C. In countries that are rendered non-endemic through diphtheria has been successfully controlled, immunity high immunization coverage, the primary vaccination levels should be maintained by booster doses. Revaccination of adults against diphtheria bibliography (and tetanus) every 10 years may be necessary to sustain 1. Bacteriological and epidemiological characteristics of immunity in some epidemiological settings. Persistence of combined diphtheria toxoid and tetanus toxoid rather diphtheria, Hyderabad, India, 2003–2006. Centers for Disease Control and Prevention: Respiratory Although most infections with C. In pre-vaccination era, diphtheria had a very corynebacterial and coryneform infections. New York: Oxford University widespread vaccination in both developed and developing Press; 1998. Diphtheria: changing patterns but there is also decrease in the circulating toxigenic in the developing world and the industrialized world. Hence the ideal public health policy should put efforts to Philadelphia: Churchill Livingstone; 2009. It is an illness lasting 6 weeks and goes Pertussis, or whooping cough, is an infection of the through catarrhal, paroxysmal, and convalescent stages, respiratory tract characterized by a paroxysmal cough. The catarrhal phase is Before the availability of a vaccine, pertussis was the similar to common upper respiratory infections with nasal major cause of morbidity and mortality among infants and congestion, rhinorrhea, sneezing, conjunctival injection children. However, pertussis still remains phase, pertussis may remain communicable for 3 or more a disease of public health concern. Paroxysmal phase presents with paroxysms of intense coughing lasting up to several minutes. In older infants and toddlers, the paroxysms of epidemiology coughing may be followed by a loud whoop as inspired air Bordetella pertussis and Bordetella parapertussis cause goes through a still partially closed airway. Bacteria spread via aerosolized droplets than 6 months have apneic episodes and are at risk for from coughing of infected individuals. Facial congestion with coughing and post- occur through direct face-to-face contact, sharing a confined tussive vomiting are common symptoms. Patients in the space, or through contact with oral, nasal, or respiratory convalescent stage have a chronic cough, which may last secretions from an infected source. Bronchopneumonia deve- or strangulation, and headaches may be seen in older lops with desquamation of the epithelium of small children, and adolescents, instead of the distinct stages. Physical examination contributes little to the diagnosis Bronchiectasis may develop and persist. Conjunctival hemorrhages and facial infants in low-income countries may be as high as 4%. Neither natural infection, nor vaccination provides lifelong Premature infants and patients with underlying cardiac, immunity. Protection against pertussis wanes 3–5 years pulmonary, neuromuscular, or neurologic disease are at high after vaccination and is not detected after 12 years. From 1980-2005, the reported incidence and adults often have mild or atypical illness. Complications among adolescents and adults include adolescents and adults, the annual reported incidence syncope, sleep disturbance, incontinence, rib fractures, and remained highest among infants less than one-year-old, at pneumonia. There is also a shift in the to have severe disease, to develop complications, and to epidemiology of pertussis, with more cases being reported require hospitalization. Pneumonia occurs in approximately in older age groups, which is due to waning immunity to 13% of infants with pertussis either from B. Infectious disease experts thought to result from severe paroxysm-induced cerebral are investigating means of preventing disease transmission hypoxia and apnea, hypoglycemia and small intracranial to infants. Reported deaths in young infants have adults in close contact with infants, maternal vaccination increased considerably over last 20 years. From 1990-1999, to provide passive antibody protection to the infant, and the case fatality rate was approximately 1% in infants vaccinating infants with pertussis vaccine at birth. The conditions that should be differentiated from per- clinical course tussis include afebrile pneumonia syndrome, bronchiolitis, It is observed that the frequency of pertussis cases in chlamydial infections, mycoplasma infections and respira- India is higher during the months of November to June. Vitals and oxygen saturation of Therefore, typical symptoms along with history of incom hospitalized patients should be monitored continuously, plete or absent pertussis vaccination, and lymphocytosis especially in relation to coughing paroxysms. The use of corticosteroids and β2-adrenergic agents A confirmed case is defined as one with any cough for the treatment of pertussis is not supported by current illness in which B. Specimen for Prevention culture is obtained by deep nasopharyngeal aspiration and inoculation in Bordet-Gengou agar, Regan-Lowe or Administration of the vaccine containing cellular and modified Stainer-Scholte media causes growth in 3–4 days. Adolescent 11 through 18 years of age this does not exclude the diagnosis of pertussis. American Academy of Pediatric Committee on Infectious are currently available for investigational use only. Prevention of pertussis among adolescents: Imaging studies typically add little to the diagnosis recommendations for use of tetanus toxoid, reduced of pertussis. Chest roentgenogram may reveal perihilar diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Red Book: 2006 Report of the Committee of Infectious pneumomediastinum or air in the soft tissues may be seen. Preventing tetanus, diphtheria, and pertussis among adults: use of management tetanus toxoid, reduced diphtheria toxoid and acellular Management aims at limiting the number of paroxysms, pertussis vaccine. Pertussis--United providing assistance when necessary, and maximizing States, 1997-2000. Pertussis and other Bordetella patients with active pertussis infections is supportive. Azithromycin is the in infants hospitalized with pertussis: a case-control study of 16 pertussis deaths in Canada. Frequent reviews are necessary based on patient’s age, from pertussis among young infants in the United States in disease severity and presence of co-morbid conditions. Acellular vaccines for of severe disease and complications, including infants preventing whooping cough in children. Cochrane Database younger than 3 months; infants aged 3–6 months, unless Syst Rev. Tetanus historically called ‘Lockjaw’ is an acute often fatal, • “Localized tetanus” produces pain and spasm of the severe exotoxin-mediated infection caused by Clostridium muscles in proximity to the site of injury. Rosenbach in 1886 demonstrated for the first time this form of disease may precede generalized form. The disease first described by Carlie • “Cephalic tetanus” is a rare form of the disease seen in and Rattone is characterized by severe muscular spasms or children with otitis media. The first sign most of the time is trismus or lockjaw due to spasm epidemiology of masseter muscle. Headache, restlessness and irritability Tetanus occurs worldwide and is an important cause may be early symptoms followed by stiffness of the of neonatal death in developing world. The causative neck, difficulty in swallowing and rigidity of abdominal organism C. The spasms can be precipitated by bright light, and animal intestines and is disseminated through the noise and even touch.

The major histologic features are sinusoidal congestion and fibrosis tadacip 20mg low cost erectile dysfunction age at onset, necrosis of pericentral hepatocytes cheap tadacip 20 mg on line impotence from diabetes, narrowing and eventually fibrosis buy generic tadacip 20mg on-line erectile dysfunction 19 years old, and obliteration of sublobular and central venules [74] tadacip 20 mg visa erectile dysfunction definition. A transjugular approach to measure the hepatic venous pressure gradient (>10 mm Hg) may have diagnostic and prognostic implications and facilitates obtaining a liver biopsy tadacip 20mg overnight delivery erectile dysfunction treatment in bangalore. Mild to moderate disease is characterized by eventual resolution of liver dysfunction tadacip 20mg lowest price erectile dysfunction viagra doesn't work, whereas severe disease is associated with multiorgan failure and a mortality rate approaching 100%. Risk factors include underlying hepatic disease, age, source of stem cells, conditioning regimen, age, sex, and metastatic malignancy. The strongest evidence exists for the use of defibrotide and ursodeoxycholic acid for prophylaxis, whereas agents such as pentoxifylline, prostaglandin E1, heparin, and antithrombin are not recommended because if mixed data and lack of randomized controlled trials [78–80]. Diagnosis is generally clinical and should be considered in any patient who presents with abdominal pain with diarrhea, classic rash, and/or rising bilirubin within 100 days following transplantation [88]. Patients who do not respond or progress within the first 5 to 7 days are considered steroid refractory and carry a poor prognosis [91]. Chronic viral hepatitis is arbitrarily defined as the presence of persistent liver inflammation, liver chemistry abnormalities, and positive serologic and molecular markers for more than 6 months. Damage to the hepatic parenchyma, with or without fibrosis, is a common outcome of chronic liver disease. Regardless of whether the insult to the hepatocytes, the biliary ducts, or the hepatic vasculature is toxic, viral, metabolic, autoimmune, or ischemic, the reparative process often leads to similar outcomes. Cirrhosis is a chronic diffuse condition characterized by replacement of liver cells by fibrotic tissue, which creates a nodular-appearing distortion of the normal liver architecture. Highly potent direct acting antivirals with cure rates >90% in most cases are creating a significant impact on patients with chronic hepatitis C [99,100]. It is the most common cause of liver cancer worldwide; and it is unevenly distributed throughout the world. In endemic areas (East Asia and sub-Saharan Africa), the infection is predominantly vertically transmitted from the mother to the infant. Although alcohol exerts a direct toxic effect on the liver, significant liver damage develops among only 10% to 20% of those patients with chronic alcohol abuse. Severe alcoholic hepatitis is a form of alcoholic liver disease associated with jaundice and coagulopathy, with a 30% to 50% 1-month mortality [104]. Alcoholic hepatitis–related hospitalization increased from 2002 to 2010, and inpatient mortality decreased during this period [105]. Alcoholic liver disease alone or in combination with other liver-related disease is one of the most common indications for liver transplant in the United States [106]. It is important to recognize acute decompensation in Wilson disease because this condition is universally fatal without a liver transplant. Clinical Manifestations and Diagnosis Clinical manifestations of chronic liver disease vary according to the functional and histologic stage of the liver disease. Physical findings described in patients with cirrhosis include temporal wasting, jaundice, telangiectasia, gynecomastia, ascites, splenomegaly, caput medusae, palmar erythema, and testicular atrophy. These markers may reflect the degree and progression of chronic liver disease and play an important role in determining patient prognosis. There is significant progress in noninvasive fibrosis staging and diagnosis of cirrhosis with the use of serum markers and tools such as elastography. Transient elastography, as approved by the Food and Drug Administration in 2013, has entered clinical practice in the United States [115]. However, liver biopsy remains the gold standard to establish the severity of liver inflammation and fibrosis. Complications and Management The four hallmark complications of cirrhosis are ascites, hepatic encephalopathy, variceal bleeding, and jaundice. The important distinction between compensated cirrhosis and decompensated cirrhosis is the appearance of one of these complications. Hospitalization at diagnosis or at any time with liver disease signals a worse prognosis independent of the cirrhosis stage [116]. Hepatic encephalopathy that ranges from subtle cerebral dysfunction to deep coma is a complication of end-stage liver disease that can result in multiple hospitalizations and decrease life quality. Clinical manifestations of portal hypertension include splenomegaly, esophageal and gastric varices, portal hypertensive gastropathy, colopathy, and ascites. Hepatic Encephalopathy Hepatic encephalopathy is a syndrome of disordered consciousness, psychiatric, neurologic, and neuromuscular abnormalities, as a result of chronic liver disease and/or portosystemic shunts [117]. Clinical features range in severity from subclinical encephalopathy, manifested by disturbances in psychometric testing to coma (see Chapters 145 and 146). Cerebral edema and elevated intracranial pressure seen with acute liver failure are not present in patients with hepatic encephalopathy and cirrhosis. However, there is poor correlation between ammonia levels and clinical disease [119], and, in many cases, results are of uncertain utility [120]. Evaluation of patients with encephalopathy should start with identification of the precipitating event. Metabolic abnormalities such as abnormal serum sodium, potassium, and glucose as well as hypoxemia should be corrected. Given the coagulopathy associated with chronic liver disease, a lumbar puncture should be pursued only if clinically imperative and after correction of blood clotting abnormalities. Medications that decrease endogenous nitrogen production and nitrogen delivery to the liver play an important role in treating encephalopathy. Lactulose is a nonabsorbable disaccharide that reduces the intestinal production and absorption of ammonia [121]. The dose of lactulose should be titrated to achieve three to five soft stools a day, starting at 30 mL orally or via nasogastric tube every 2 to 4 hours. Lactulose can also be given as an enema in patients with an ileus or in those at increased risk of aspiration (300 mL lactulose in 700 mL distilled water). Rifaximin is a nonabsorbable rifamycin antibiotic that should be added to lactulose if symptoms persist; it has been shown to maintain remission from hepatic encephalopathy and reduce hospitalization related to hepatic encephalopathy [122]. Before rifaximin became available, neomycin and metronidazole have been used in addition to lactulose and may be used as an adjunct in resource-limited setting or where rifaximin is not available. However, side effects such as ototoxicity and nephrotoxicity (neomycin) and peripheral neuropathy and dysgeusia (metronidazole) limit their widespread and long-term use. Oral branched chain amino acids improve manifestations of hepatic encephalopathy without any effects on survival [123]. Large spontaneous portosystemic shunts may occur in patients with refractory hepatic encephalopathy, and embolization of these shunts may be safe and effective [126]. Variceal Bleeding Portal hypertension is characterized by increased resistance to portal flow and increased portal venous inflow owing to splanchnic dilatation. Portal hypertension is defined by measuring the pressure difference between the hepatic vein and the portal vein (normal pressure gradient 3 mm Hg) through transjugular approach. Portal hypertension induces hemodynamic changes in the hepatic and splanchnic blood flow, with the development of portosystemic collateral circulation (esophagus, stomach, rectum, umbilicus, and retroperitoneum) and splenomegaly. Primary prophylaxis is recommended for patients with small varices with red wale signs or in patients with large varices. The bleeding event is often dramatic and associated with severe hemodynamic instability and frequently followed by hepatic encephalopathy. Caution against over transfusion is warranted, with recent evidence showing higher mortality in patients who were liberally transfused (hemoglobin > 9 mg per dL) compared to the patients who were judiciously transfused (hemoglobin > 7 mg per dL) [131]. This technique was initially used in Japan and Korea but is becoming increasingly available in the United States. The coagulation profile of a patient with chronic liver disease is significantly different from a normal patient because there are deficiencies in the synthesis of coagulation factors in both procoagulant and anticoagulant pathways [133]. Transfusion-related lung injury is a dangerous consequence of overtransfusion and can progress to acute lung injury and acute respiratory distress syndrome. Thrombocytopenia is common among patients with splenomegaly secondary to cirrhosis, and it is a consequence of hypersplenism. In our experience, transfusion of platelets should be limited to those patients who are actively bleeding or undergoing an invasive procedure. Ascites, Hydrothorax, and Hyponatremia Mechanisms responsible for the formation of ascites are complicated, multifactorial, and result in sodium and water retention. Circulatory dysfunction characterized by arterial vasodilation and low peripheral vascular resistance with hypotension, high cardiac output, and hypervolemia is seen in patients with portal hypertension and ascites. Levels of nitric oxide, a potent vasodilator, are elevated in the splanchnic circulation of patients with ascites. The ensuing arterial vasodilation triggers activation of baroreceptor-mediated systems, the renin– angiotensin–aldosterone system, and the sympathetic nervous system, inducing sodium retention. The major clinical consequence of this elevation is dilutional hyponatremia, which occurs despite an avid sodium state [134].

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