Ulcerative colitis - Chrons disease

Ulcerative colitis

Inflammatory bowel disease is thought to result

from inappropriate and ongoing activation of the mucosal

immune system driven by the presence of normal

luminal flora.

the absolute risk of inflammatory bowel disease

is approximately 7 percent among first-degree

family members. Collectively, these findings lend compelling support

to the inference that susceptibility is inherited

and that the genetic contribution to the development

of disease is more important in Crohn’s disease than

in ulcerative colitis.

This gene encodes

a cytoplasmic protein designated NOD2 (also referred

to as CARD 15 [caspase activation and recruitment

domain]), which is expressed in macrophages and may

serve as a so-called pattern-recognition receptor for

bacterial lipopolysaccharide, perhaps regulating nuclear

factork B activation and macrophage apoptosis.

“only” 45 percent of pairs

of identical twins are concordant for Crohn’s disease. early appendectomy, which is associated with a reduced incidence of ulcerative colitis. Smoking may

modify the phenotype; it protects against ulcerative

colitis but increases the risk of Crohn’s disease.

Rta immune: In contrast, the mucosa in patients with ulcerative colitis

may be dominated by CD4+ lymphocytes with an

atypical type 2 helper-T-cell (Th2) phenotype, characterized by the production of transforming growth factorb(TGFb) and interleukin-5 but not interleukin-4

The activation of central immune-cell populations

is eventually accompanied by the production of a wide

variety of nonspecific mediators of inflammation (Fig.

2). These include many other cytokines, chemokines,

and growth factors as well as metabolites of arachidonic

acid (e.g., prostaglandins and leukotrienes) and

reactive oxygen metabolites such as nitric oxide. T_H2 cells and related natural killer T cells that secrete IL-13 induce superficial mucosal inflammation resembling UC, and T_H17 cells may be responsible for neutrophilic recruitment. in an IBD patient, the normal flora is likely perceived as if it were a pathogen. Anaerobic organisms, particularly Bacteroides and Clostridia species, and some aerobic species such as Escherichia may be responsible for the induction of inflammation.

UC is a mucosal disease that usually involves the rectum and extends proximally to involve all or part of the colon. About 40–50% of patients have disease limited to the rectum and rectosigmoid, 30–40% have disease extending beyond the sigmoid but not involving the whole colon, and 20% have a total colitis. Proximal spread occurs in continuity without areas of uninvolved mucosa. When the whole colon is involved, the inflammation extends 1–2 cm into the terminal ileum in 10–20% of patients. This is called backwash ileitis and is of little clinical significance. Although variations in macroscopic activity may suggest skip areas, biopsies from normal-appearing mucosa are usually abnormal. Thus, it is important to obtain multiple biopsies from apparently uninvolved mucosa, whether proximal or distal, during endoscopy.

With mild inflammation, the mucosa is erythematous and has a fine granular surface that looks like sandpaper. In more severe disease, the mucosa is hemorrhagic, edematous, and ulcerated (Fig. 289-1). In long-standing disease, inflammatory polyps (pseudopolyps) may be present as a result of epithelial regeneration. The mucosa may appear normal in remission, but in patients with many years of disease it appears atrophic and featureless and the entire colon becomes narrowed and shortened. Patients with fulminant disease can develop a toxic colitis or megacolon where the bowel wall thins and the mucosa is severely ulcerated; this may lead to perforation.

Clinical

The major symptoms of UC are diarrhea, rectal bleeding, tenesmus, passage of mucus, and crampy abdominal pain. The severity of symptoms correlates with the extent of disease. Although UC can present acutely, symptoms usually have been present for weeks to months. Occasionally, diarrhea and bleeding are so intermittent and mild that the patient does not seek medical attention. Patients with proctitis usually pass fresh blood or blood-stained mucus, either mixed with stool or streaked onto the surface of a normal or hard stool. They also have tenesmus, or urgency with a feeling of incomplete evacuation, but rarely have abdominal pain. With proctitis or proctosigmoiditis, proximal transit slows, which may account for the constipation commonly seen in patients with distal disease. When the disease extends beyond the rectum, blood is usually mixed with stool or grossly bloody diarrhea may be noted. Colonic motility is altered by inflammation with rapid transit through the inflamed intestine. When the disease is severe, patients pass a liquid stool containing blood, pus, and fecal matter. Diarrhea is often nocturnal and/or postprandial. Although severe pain is not a prominent symptom, some patients with active disease may experience vague lower abdominal discomfort or mild central abdominal cramping. Severe cramping and abdominal pain can occur with severe attacks of the disease. Other symptoms in moderate to severe disease include anorexia, nausea, vomiting, fever, and weight loss.

Ulcerative Colitis

Patients with long-standing UC are at increased risk for developing colonic epithelial dysplasia and carcinoma (Fig. 289-9).

The risk of neoplasia in chronic UC increases with duration and extent of disease. The risk of cancer rises 0.5–1% per year after 8–10 years of disease in patients with pancolitis. The only prospective surveillance study reported a lower rate of cancer; 2.5% at 20 years of disease, 7.6% at 30 years of disease, and 10.8% at 40 years. The rates of colon cancer are higher than in the general population, and colonoscopic surveillance is the standard of care

Otitis Media

Family socioeconomic status and the extent of exposure to other children constitute the 2 most important identifiable risk factors for developing OM.

The term otitis media has 2 main components: acute infection, which is termed suppurative or acute otitis media (AOM); and inflammation accompanied by effusion, termed nonsuppurative or secretory otitis media, or otitis media with effusion (OME). These 2 main types of OM are interrelated: acute infection usually is followed by residual inflammation and effusion that, in turn, predispose children to recurrent infection. Middle-ear effusion (MEE) is a feature of both AOM and OME; in both conditions, is an expression of the underlying middle-ear mucosal inflammation. In children with OM, mucosal inflammation also is present in the mastoid air cells, which are in continuity with the middle-ear cavity

Acute Otitis Media.

Pathogenic bacteria can be isolated by standard culture techniques from middle-ear fluid in approximately 65–75% of cases of well-documented AOM; in the remaining cases, bacterial culture shows either no growth or the presence of organisms generally considered nonpathogenic. Three pathogens predominate:S. pneumoniae is found in approximately 40% of cases; nontypable Haemophilus influenzae in approximately 25–30%; and Moraxella catarrhalis in approximately 10–15%. Other pathogens that, together, account for approximately 5% of cases include group A streptococcus, Staphylococcus aureus, and gram-negative organisms. S. aureus and gram-negative organisms are found most commonly in neonates and very young infants who are hospitalized. In outpatient settings, the distribution of pathogens in these young infants is similar to that in older infants

Under usual circumstances, the eustachian tube is passively closed and is opened by contraction of the tensor veli palatini muscle. of this ventilatory process by tubal obstruction initiates a complex inflammatory response that includes secretory metaplasia, compromise of the mucociliary transport system, and effusion of liquid into the tympanic cavity.

In children with cleft palate, where OM is a nearly universal finding, the main factor underlying the chronic middle-ear inflammation is impairment of the opening mechanism of the eustachian tube, due perhaps to greater-than-normal compliance of the tubal wall

In a study of children in group daycare, AOM was observed in approximately 30–40% of children with respiratory illness caused by RSV, influenza viruses, or adenoviruses, and in approximately 10–15% of children with respiratory illness caused by parainfluenza viruses, rhinoviruses, or enteroviruses. Viral infection of the upper respiratory tract results in release of cytokines and inflammatory mediators, some of which may cause eustachian tube dysfunction

CLINICAL MANIFESTATIONS: There may be evidence of ear pain, often manifested by irritability, a change in sleeping or eating habits, and, occasionally, holding or tugging at the ear. Pulling at the ear, however, has a low sensitivity and specificity. Fever also may be present and, rarely, rupture of the tympanic membrane with purulent otorrea. This hearing loss. Balance lost

Important characteristics of the tympanic membrane include contour, color, translucence, structural changes, if any, and mobility. Normally the contour of the membrane is slightly concave; abnormalities consist of fullness or bulging, or conversely, extreme retraction. The normal color of the tympanic membrane is pearly gray. Erythema may be a sign of inflammation or infection, but unless it is intense, erythema alone may result from crying or vascular flushing. Abnormal whiteness of the membrane may result from either scarring or the presence of liquid in the middle-ear cavity; liquid also may impart an amber, pale yellow, or (rarely) bluish color. Normally, the membrane is translucent, although some degree of opacity may be normal in the first few mo of life; later, opacification denotes either scarring, or more commonly, underlying effusion. Structural changes include scars, perforations, retraction pockets, and a more severe complication of OM, cholesteatoma formation. Of all the visible characteristics of the tympanic membrane, mobility is the most sensitive and specific in determining the presence or absence of MEE. Importantly, mobility is not an all-or-none phenomenon; although total absence of mobility, in the absence of a tympanic membrane perforation, virtually always is indicative of MEE, substantial impairment of mobility is the more common finding.

TABLE 639-1 -- Definition of Acute Otitis Media

A diagnosis of AOM requires (1) a history of acute onset of signs and symptoms,(2) the presence of MEE, and (3) signs and symptoms of middle-ear inflammation.

The definition of AOM includes:

Recent, usually abrupt, onset of signs and symptoms of middle-ear inflammation and MEE

The presence of MEE, indicated by any of the following:

Bulging of the TM

Limited or absent mobility of the TM

Air-fluid level behind the TM

Otorrhea

Signs or symptoms of middle-ear inflammation, indicated by either

Distinct erythema of the TM, or

Distinct otalgia (discomfort clearly referable to the ear[s] that results in interference with or precludes normal activity or sleep)

Distinguishing between AOM and OME on clinical grounds also is straightforward in most cases, but because each condition may evolve into the other without any clearly differentiating physical findings, any schema for distinguishing between them is, to some extent, arbitrary. Nonetheless, in an era of increasing bacterial resistance, distinguishing between AOM and OME has become increasingly important in determining treatment. Obviously, purulent otorrhea of recent onset is indicative of AOM; thus, difficulty in distinguishing clinically between AOM and OME is limited to circumstances in which purulent otorrhea is not present. Both AOM without otorrhea and OME are accompanied by physical signs of MEE, i.e., the presence of at least 2 of 3 tympanic membrane abnormalities: white, yellow, amber, or (rarely) blue discoloration; opacification other than that due to scarring; and decreased or absent mobility. Alternatively, in OME either air-fluid levels or air bubbles outlined by small amounts of fluid may be visible behind the tympanic membrane, a condition often indicative of impending resolution.

To support a diagnosis of AOM instead of OME in a child with MEE, distinct fullness or bulging of the tympanic membrane may be present, with or without accompanying erythema. At minimum, MEE should be accompanied by ear pain that appears clinically important. Unless intense, erythema alone is insufficient; erythema without other abnormalities may result from crying or vascular flushing. In AOM, the malleus may be obscured, and the tympanic membrane may resemble a bagel with a central depression rather than a hole ( Fig. 639-2 ). Rarely, the tympanic membrane may be obscured by surface bullae, or may have a cobblestone appearance. Bullous myringitis is a physical manifestation of AOM, not an etiologically discrete entity. Fullness of the membrane may diminish within days after onset, even though infection may still be present.

In OME, bulging of the tympanic membrane is absent or slight, or the membrane may be retracted ( Fig. 639-3 ); erythema also is absent or slight, but may increase with crying or with superficial trauma to the external auditory canal incurred in clearing the canal of cerumen. In children with MEE but without tympanic membrane fullness or bulging, the presence of unequivocal ear pain usually is indicative of AOM

TABLE 639-2 -- Criteria for Initial Antibacterial-Agent Treatment or Observation in Children With AOM

AGE	CERTAIN DIAGNOSIS	UNCERTAIN DIAGNOSIS
<6>	Antibacterial therapy	Antibacterial therapy
6 mo–2 y	Antibacterial therapy	Antibacterial therapy if severe illness; observation option[*] if nonsevere illness
≥2 y	Antibacterial therapy if severe illness; observation option[*] if nonsevere illness	Observation option[*]

The most important aspect of these guidelines is that close follow-up of the patient must be ensured to assess for lack of spontaneous resolution or worsening of symptoms and that patients should be provided with adequate analgesic medications—acetaminophen or ibuprofen—during the period of observation. Topical otic agents (e.g., Auralgen) also may be effective for pain relief. When pursuing the practice of watchful waiting in patients with AOM, the certainty of the diagnosis, the patient's age, and the severity of the disease should be considered

La apariencia tóxica es la presentación clínica

caracterizada por letárgica, pobre contacto

visual, pobre perfusión periférica, irritabilidad,

cianosis, hipo o hiperventilación. Numerosos

estudios concluyen en que el aspecto tóxico

o séptico del niño es un buen predictor de

enfermedad.

For younger patients, <2 style="background: yellow none repeat scroll 0% 0%; -moz-background-clip: border; -moz-background-origin: padding; -moz-background-inline-policy: continuous;">In very young patients, <6>. In children 6–24 mo of age who have a questionable diagnosis of OM but are severely ill, defined as temperature of >102°F (>39°C), significant otalgia, or toxic appearance, antibiotic therapy is also recommended. However, children in this age group in whom the diagnosis is questionable and the disease is not severe can be observed for a period of 2–3 days with close follow-up. In children >2 yr of age, observation might be considered in all episodes of non-severe OM or episodes of questionable diagnosis, with antibiotic therapy reserved for confirmed, severe episodes of AOM

TABLE 639-3 -- Recommended Antibacterial Agents for Patients Who Are Being Treated Initially With Antibacterial Agents or Have Failed 48 to 72 Hours of Observation or Initial Management With Antibacterial Agents

TEMPERATURE ≥39°C AND/OR SEVERE OTALGIA	AT DIAGNOSIS FOR PATIENTS BEING TREATED INITIALLY WITH ANTIBACTERIAL AGENTS		CLINICALLY DEFINED TREATMENT FAILURE AT 48–72 HR AFTER INITIAL MANAGEMENT WITH OBSERVATION OPTION		CLINICALLY DEFINED TREATMENT FAILURE AT 48–72 HR AFTER INITIAL MANAGEMENT WITH ANTIBACTERIAL AGENTS
	RECOMMENDED	ALTERNATIVE FOR PENICILLIN ALLERGY	RECOMMENDED	ALTERNATIVE FOR PENICILLIN ALLERGY	RECOMMENDED	ALTERNATIVE FOR PENICILLIN ALLERGY
No	Amoxicillin, 80–90 mg/kg per day	Non–type 1:cefdinir, cefuroxime, cefpodoxime; type 1:azithromycin, clarithromycin	Amoxicillin, 80–90 mg/kg per day	Non–type 1:cefdinir, cefuroxime, cefpodoxime; type 1:azithromycin, clarithromycin	Amoxicillin-clavulanate, 90 mg/kg per day of amoxicillin component, with 6.4 mg/kg per day of clavulanate	Non-type 1:ceftriaxone, 3 days; type 1:clindamycin
Yes	Amoxicillin-clavulanate, 90 mg/kg per day of amoxicillin, with 6.4 mg/kg per day of clavulanate	Ceftriaxone, 1 or 3 days	Amoxicillin, clavulanate, 90 mg/kg per day of amoxicillin, with 6.4 mg/kg per day of clavulanate	Ceftriaxone, 1 or 3 days	Ceftriaxone, 3 days	Tympanocentesis, clindamycin

From Subcommittee on Management of Acute Otitis Media: Diagnosis and management of acute otitis media. Pediatrics 2004;113:1451–1465.

Although antimicrobial resistance rates vary from country to country, in the USA approximately 40% of strains of nontypable H. influenzae and almost all strains of M. catarrhalis currently are resistant to aminopenicillins (e.g., ampicillin, amoxicillin). Approximately 50% of strains of S. pneumoniae are penicillin-nonsusceptible, divided approximately equally between penicillin-intermediate and, even more difficult to treat, penicillin-resistant strains. Resistance to macrolides, including azithromycin and clarithromycin, by S. pneumoniae has been increasing rapidly, and approximately 30% of strains are macrolide-resistant. Two mechanisms of macrolide resistance have been identified: the first, mediated by the mef(A) gene, involves an efflux pump that decreases intracellular accumulation of macrolides and results in low-level resistance; the second mechanism, mediated by the erm(B) gene, involves production of ribosomal methylases that modify ribosomal RNA and result in high-level resistance. The latter mechanism also results in resistance to clindamycin, which otherwise is generally effective against resistant strains of S. pneumoniae.

Amoxicillin is the most efficacious of available oral antimicrobial drugs against both penicillin-susceptible and penicillin-nonsusceptible strains of S. pneumoniae. Increasing the dose from the traditional 40 mg/kg/24 hr to 80–100 mg/kg/24 hr usually is effective against penicillin-intermediate and some penicillin-resistant strains. Drugs chosen for second-line treatment should be effective against β-lactamase–producing strains of H. influenzae and M. catarrhalis and against susceptible and most nonsusceptible strains of S. pneumoniae. Only 3 drugs have been shown clearly to meet that requirement: amoxicillin-clavulanate, cefuroxime axetil, and intramuscular ceftriaxone.

Indications for myringotomy in children with AOM include severe, refractory pain; hyperpyrexia; complications of AOM such as facial paralysis, mastoiditis, labyrinthitis, or central nervous system infection; and immunologic compromise

Bacteriology of middle ear fluid specimens obtained by tympanocentesis from 111 Colombian children with acute otitis media.

Trujillo H, Callejas R, Mejía GI, Castrillón L.

Corporación para Investigaciones Biológicas, Pablo Tobón Uribe Hospital, Medellín, Colombia.

We cultured middle ear fluid specimens obtained by tympanocentesis from 111 Colombian infants and children, ages 11 days to 11 years, with acute otitis media. Bacteria were isolated in 82 patients (74%). Haemophilus influenzae, the most common isolate, was present in 40 cases (36%); 32 were nontypable strains and 8 were type b. Streptococcus pneumoniae, identified in 26 cases (22%), was the second most common pathogen. All H. influenzae and S. pneumoniae strains were susceptible to ampicillin and penicillin, respectively. We conclude that amoxicillin remains the drug of choice for treatment of acute otitis media in our country.