-------------------------------------------------------------------------------- TITLE: OTOLARYNGOLOGIC MANIFESTATIONS OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds DATE: APRIL 22, 1992 RESIDENT PHYSICIAN: Joseph J. Bradfield, M.D. FACULTY: Karen H. Calhoun, M.D. DATABASE ADMINISTRATOR: Melinda McCracken, M.S. -------------------------------------------------------------------------------- "This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." I. BACKGROUND In the late 70's physicians began to see a number of patients with symptoms consistent with severe immunodeficiency, but without reason for immunosuppression. Initially sexually active homosexual males, and later intravenous drug abusers and users of blood products, presented with Kaposi's sarcoma, mucocutaneous candidiasis, Pneumocystis pneumonia and other diseases usually found only in those with severely compromised T lymphocyte function. The disease was dubbed the acquired immunodeficiency syndrome (AIDS). The causative virus - the human immunodeficiency virus (HIV) has subsequently been identified. The disease is probably THE significant illness of the 20th century, and now constitutes a worldwide pandemic. Our understanding of the HIV and of the mechanisms of AIDS related illnesses is not complete, and continues to evolve almost daily. AIDS has spawned a crisis in public health, and raised numbers of social concerns about the treatment of AIDS victims, controlling the spread of the disease, and the risk to health care workers from AIDS victims, as well as to the public from infected health care workers. Almost two-thirds of AIDS patients will manifest the disease in the head and neck. It is therefore essential that the practicing otolaryngologist have a good grasp of the common presentation, diagnosis and treatment of AIDS related illnesses in the head and neck. II. EPIDEMIOLOGY A. Incidence and Prevalence 1. The first AIDS case was reported in June 1981. By December 31, 1991, over 205,000 cases of full blown AIDS had been reported, with 133,232 deaths. Indicative of the escalation of the AIDS epidemic in the U.S., the first 100,000 cases were reported over an 8 year period, and the second 100,000 in only a 2 year period. By 1993 it is estimated that there will have been almost 500,000 cases and 350,000 deaths. 2. The CDC estimates that in addition to the reported cases, an estimated 1,000,000 Americans are infected with HIV. AIDS will develop in most - if not all. Current estimates are that 1 of every 100 adult males and one of every 800 adult females are infected. In certain locations 1 of every 5 emergency room patients are estimated to be infected. B. Demographics 1. Homosexual and bisexual males continue to comprise the majority of AIDS cases (59%), followed by IV drug users (22%). Other at risk groups include the female sexual partners of IV drug abusers, hemophiliacs (2.2%), and children of HIV positive mothers - who now comprise about 10% of cases. 2. Women comprise about 10-11% of cases. 34% of AIDS cases in women are linked to heterosexual transmission. 3. Blacks and Hispanics are disproportionately infected - 29% and 16% of all cases respectively. C. Trends 1. The rate of spread of AIDS in homosexuals has declined, as the rate of heterosexual transmission has accelerated. In some inner-city areas, heterosexual transmission is now the dominant route of spread. (Heterosexual transmission is also the dominant mode of spread in the third world, where the male:female ratio is almost 1:1.) 2. The proportion of AIDS cases related to exposure to contaminated transfusion products has declined sharply with the advent of antibody screening of donors. Cases associated with transfusion will continue to arise due to: a. The long latency between infection with HIV and the development of AIDS - up to 9 years or more. b. Units obtained from individuals early in their infection who are not yet seropositive. D. Progression to AIDS 1. Fifty percent of males infected with HIV progress to AIDS within 7 years of seroconversion. Progression is more rapid in children. 2. Virus burden, strain virulence, race, sex and geographic location appear to influence the rate of progression to AIDS. Co- infection with other organisms may affect progression through a mechanism yet to be elucidated. 3. Zidovudine (AZT) appears to slow the progression of disease and increase the symptom free period. Some studies have questioned whether AZT increases absolute survival, but the latest studies show this may be the case. III. DEFINITION OF AIDS A. AIDS - For purposes of reporting AIDS cases, the CDC defines the illness as being present when certain "indicator" diseases are diagnosed, and depending on the status of laboratory tests for the presence of HIV infection. Specific disease are notable complications of the immunocompromised status of infected individual and include certain bacterial infections in children, opportunistic fungal, parasitic viral and bacterial infections that take advantage of decreased T-cell function, B-cell lymphomas, AIDS encephalopathy (attachment 1). The case definition is currently under revision to facilitate more complete reporting. B. ARC - The AIDS-Related Complex (ARC) includes patients with milder symptoms including adenopathy, fevers, weight loss, or thrush. IV. VIROLOGY A. General 1. HIV-1 is one of five human retroviruses, of which three are known causes of human disease. Spread is via sexual transmission, transmission through blood and blood products, contaminated needles, and congenital transmission. 2. The lifecycle of retroviruses is unique, and includes reverse transcription of RNA into DNA, with integration in the host genome. Later expression of the genome allows assembly and release of viruses by budding or cell lysis. This ability to form latent infection allows the virus to cause disease with a long latency period. B. Pathogenesis 1. HIV preferentially infects nervous system and lymphatic system cells. The most important cell infected is the T-helper cell, with the virus apparently gaining entry through the CD4+ receptor. The eventual result is both functional impairment and numeric depletion of T helper cells. 2. T lymphocyte subset analysis is therefore the most useful measure of immune function in AIDS. Specific complications can be anticipated by following T-cell counts. a. T-helper counts between 200 and 500/mm3 are associated with tuberculosis, hairy leukoplakia and Kaposi's Sarcoma. b. Counts less than 200 increase risk of pneumocystis infection and TMP-SMX prophylaxis should be considered. 3. As is true with many other viruses, HIV also produces a primary neuropathy, cardiomyopathy, dementia, wasting syndrome, as well as other disorders. 4. It is currently estimated that 40 - 70% of all patients with AIDS initially present with head and neck manifestations. V. GENERAL PATHOLOGY OF AIDS IN THE HEAD AND NECK A. General - As a result of the immunosuppression caused by the HIV, AIDS patients are susceptible to a broad range of infectious agents. Most of the infections have reported head and neck manifestations. B. Protozoan Infections 1. Pneumocystis carinii is the opportunistic pathogen most commonly associated with AIDS, and is the most common life threatening infection in the disease. Pneumocystis disease is only rarely found outside the pulmonary system, but is increasingly reported in the external ear and thyroid. As a rule, pulmonary manifestations precede extrapulmonary involvement, but cases have been reported in which extrapulmonary Pneumocystis infection was the presenting complaint in a new AIDS patient. Histologic evaluation shows a foamy eosinophilic infiltrate, and methenamine silver stains will demonstrate the organism (Grocotts stain). Treatment for pneumocystis infections is with TMP/SMX. Inhaled aerosolized pentamidine may be of benefit in certain cases of pulmonary pneumocystis. There is some evidence that the use of aerosolized pentamidine may be contributing to the rise in extrapulmonary pneumocystis infections. 2. Toxoplasma encephalitis may occur in up to 40% of AIDS patients and usually represents a recrudescence of cystic disease. Biopsy specimen will demonstrate cysts and tachyzoites with a usually marked inflammatory response. Combination sulfadiazine and pyrimethamine are used for treatment. 3. Cryptosporidium and Isospora are two coccidian protozoans associated with debilitating enteritis in AIDS. Specific head and neck manifestations have not been described. There is no effective treatment for cryptosporidium. Isospora usually responds to TMP/SMX. C. Viruses - Viral infections are commonly seen in the head and neck in AIDS patients. The DNA viruses are most commonly identified - cytomegalovirus (CMV), Herpesviruses (HSV and VZV), Epstein-Barr virus (EBV), and papilloma virus (HPV). 1. CMV is the opportunistic pathogen most commonly identified at autopsy. Head and neck CMV infection is uncommon in the general population. In AIDS, it is usually seen as an ulcerative mucocutaneous lesion. The characteristic histology shows ulceration, necrosis, and cytomegaly, with intra-nuclear or intra- cytoplasmic inclusions. Immunofluorescence can be used to confirm the infection. Gancyclovir is the drug of choice, especially, for CMV retinitis. 2. HSV is a frequent cause of mucocutaneous disease in AIDS. In the general population, HSV infection tends to be localized, while it may be widespread and disseminates in the immunocompromised. Histology shows acantholysis and degeneration of epithelial cells with intranuclear inclusions. Multinucleated cells may be common. VZV may arise in dermatomal distribution (shingles) or as Ramsay Hunt syndrome. Histology is indistinguishable from VZV. Herpesvirus infections may be treated with acyclovir. 3. EBV causes fever, fatigue, and adenopathy in non-AIDS patients. Although its role as a pathogen in AIDS is being clarified, it has been associated with oral hairy leukoplakia, lymphoproliferative disorders and Burkitts lymphoma. The association of EBV with nasopharyngeal carcinoma seen in non- immunocompromised patients has not been demonstrated in AIDS. 4. HPV is associated with condyloma and some epithelial hyperplasia, and may play a role in the development of epithelial malignancy. D. Bacterial Infections 1. Mycobacterial infections are seen in high frequency in AIDS. M. tuberculosis and M. avian intracellulare are the common organisms. Histology shows replacement of normal cellular architecture with confluent caseating granulomas. Giant cells are seen, and acid fat stain will demonstrate the organisms within giant cells or histiocytes. Combination chemotherapy is required, and strains resistant to multiple first line drugs (INH, rifampin, pyrazinamide, and streptomycin) are emerging. 2. A rise in syphilis has been noted since the onset of the AIDS epidemic. HIV associated syphilis tends to appear in atypical presentations, with shorter incubation periods, with altered serologic response, and may not respond to conventional antisyphilis therapy. Treatment is described below. 3. Other bacterial infections commonly found in the head and neck also occur in AIDS, although it has not been shown whether there is an increased frequency (except see below regarding children). These infections have a greater tendency to become disseminated. E. Mycoses 1. Candida species are the most important fungal infection in the head and neck in HIV positive patients, and its presence may herald the progression to AIDS. Candida infection is found in 75% of AIDS patients at some point in their illness. It most commonly appears as a cheesy mucosal plaque, although an atrophic form is also commonly found, with mucosal erythema. Budding yeast and pseudohyphae are found on histologic section. 2. Cryptococcus has been reported as one of the initial infections in up to half of all AIDS infections, although other series place the incidence much lower. It is the second most common cause of neurologic disease in AIDS, and the fungus shows marked tropism for the CNS. Pathologic evaluation shows infection and inflammation with vasculitis and varying degrees of tissue response. India ink stain will demonstrate the organisms in biopsy specimens. Dictum is that these patients die quickly. Treatment is combined amphotericin and 5-flucytosine. 3. Histoplasma is increasingly recognized as a pathogen in those living in endemic areas. Manifestations range from mucosal ulcers to a wide variety of mucocutaneous lesions - patches, pustules, nodules and ulcers. Diagnosis is made with culture or the demonstration of typical H. capsulatum cells on biopsy. Ketoconazole is associated with an unacceptable failure rate. Main drug is amphotericin. 4. Coccidioides infection occurs in patients from endemic areas such as the Southwestern United States. An estimated 20% of the AIDS patients in Arizona have had coccidioides infection. Head and neck manifestations including adenopathy, skin lesions and CNS involvement have been reported. Diagnosis is made on cytologic or histologic evaluation. Amphotericin is preferred therapy. 5. Numerous other mycotic infections occur with varying incidence, including aspergillosis, dermatophytoses, and others. Documentation of presenting complaints and culture results vary. F. Lymphoproliferative Disorders 1. Due to the high lymphatic content of the head and neck, people at risk for AIDS are likely to present with a variety of lymphatic disorders, ranging from persistent generalized adenopathy to lymphoid atrophy to lymphoma. Histologic findings will vary with the type and severity of the disease. 2. Reactive lymphoproliferative disease - The lymph node histologic findings in persistent generalized lymphadenopathy (PGL) reflect a spectrum of the HIV infection. Type I consists of germinal center hyperplasia, is associated with ARC, and probably represents response to HIV antigens. Type II is also associated with ARC, but is also linked with the development of AIDS. In Type II architecture there is either atrophy or absence of the germinal centers. In Type III pattern there is invariable lack of germinal centers, with histiocytosis, reduction of lymphocytes and often increased plasma cells. 3. Lymphoma - AIDS patients have an increased risk for lymphomas. Up to 10% of seropositive patients will develop some sort of lymphoma. Although all types have been reported, as a rule lymphomas in HIV positive patients tend to be high-grade, aggressive, B-cell tumors with a predisposition for extranodal sites - e.g. bone marrow, skin, liver, GI tract and CNS. Most AIDS related lymphomas occur in the oral cavity. G. Kaposi's Sarcoma (KS) - In AIDS, as opposed to classic or endemic KS, KS tends to be more aggressive, characteristically progressive, and rapidly fatal. Epidemic KS in the head and neck may present as mucocutaneous or nodal lesions, with symptoms related to the site of the lesion. Histopathology varies with the stage of disease, from slight increases in vascular space in early disease, to the dense spindle cell proliferation with near obliteration of the vascular spaces seen in advanced nodular disease. Treatment depends upon the amount of disease, and the patients overall status, and ranges from no treatment to local treatment with excision (argon laser useful) in those with one or two lesions and indolent disease, to single and multiagent chemotherapy (vinblastine, doxyrubicin) plus XRT in more advanced disease. Interferons have also been used with some success. VI. OTOLOGIC MANIFESTATIONS OF AIDS A. General - Otologic complaints are common in AIDS. In Kohan's small review (26 patients), the most common complaints were hearing loss (62%), otalgia (50%), otorrhea (31%), vertigo (15%), tinnitus (15%), and masses. Patients with otologic complaints require full otologic evaluation, with treatment principles in general the same as for the population at large. Kohan also notes that CT scanning has been proven a useful, non-invasive diagnostic tool, with indications the same as for other ear complaints: 1. When a vascular, expansile or destructive lesion is suspected. 2. When the extent of pathology cannot be determined. 3. In the case of SNHL to look for possible retrocochlear pathology - e.g. toxoplasma or cryptococcus abscesses. B. Otitis externa in AIDS tends to be similar to infection found in non-immunocompromised individuals. Pseudomonas aeruginosa tends to be the primary infecting organism. Treatment is as for normal individuals - aural toilet and topicals. There does not appear to be an increased risk for malignant otitis externa or osteomyelitis of the skull base. Less frequently, P. carinii has been identified in external canal infections. Lucente has had several patients with severe persistent fungal OE which has required intensive local and systemic therapy. C. Acute Otitis Media in AIDS tends to parallel AOM in the population at large, with S. pneumo, H. flu and B. catarrhalis predominating. There is currently no evidence of an increased attack rate of AOM in AIDS patients. Infection responds to usual antibiotic therapy, and failure to improve should prompt tympanocentesis and switch to beta-lactam resistant antibiotics. Recurrent AOM and COME have not been well studied in AIDS, but their presence is an indication for nasopharyngeal examination to rule out hypertrophic lymph node tissue or KS. D. Chronic Otitis Media has also not yet been shown to occur more often in AIDS patients. However, although Pseudomonal chronic otitis is not common, there are multiple reports of P. carinii infected polyps. Symptoms include otalgia, mixed hearing loss, and external or middle ear masses. Aural polyps should be biopsied, and on silver stain will demonstrate the characteristic organisms. P. carinii otitis is usually associated with pulmonary involvement, but may precede it. Treatment is with ten day to three weeks of TMP/SMX, and consideration should be given to the presence of subclinical pulmonary disease. Tuberculous Otitis may present with a chronically draining ear as well. Classically described clinical presentation included painless otorrhea, multiple TM perforations, abundant granulations, early severe hearing loss, and bony erosion. More recent data (Yaniv) indicate that the otorrhea may in fact be painful, and that the multiple perforations are not commonly seen. Further, bony erosion was infrequent. Instead, exposure of a bare malleus handle without soft tissue covering was considered pathognomonic. Severe conductive loss was present in 81% of the involved ears. E. Ramsay Hunt syndrome does not appear to be more common in AIDS, although there are reports of cases of bullous myringitis responsive only to acyclovir. Mishell reported a case of Ramsay Hunt Syndrome in an AIDS patient that disseminated throuout the patients body. Treatment for zoster is as for the immunocompetent. F. Sensorineural hearing loss is common in AIDS due to infection with HIV itself, infection with other organisms, and the administration of ototoxic medications. SNHL is noted to be more common than conductive loss. Meningitic causes include cryptococcus - reported to cause SNHL in 25% of patients, tuberculosis, and bacterial and viral meningitis. 1. From 23-29% of AIDS patients suffer from SNHL. One post- mortem study showed neuropathic changes in 2/3 of those with HIV infection, but only 1/3 had symptomatic SNHL at the time of death. The degree and range of loss are variable. 2. In general, high frequencies are more affected, and ABR demonstrates increased latencies, implying central etiology. 3. SNHL is less likely to respond to treatment than CHL. G. Otosyphilis occurs in the tertiary stage of the disease with complaints similar to hydrops - uni- or bi-lateral SNHL which may progress rapidly, Tinnitus, pressure and vestibular symptoms. Diagnosis is made on serology - RPR or VDRL tests may be negative in latent infection whereas the FTA-ABS remains positive for life. Otosyphilis may occur in all stages of AIDS, and should always be considered in HIV positive patients with otologic complaints. Further, otosyphilis may occur in accelerated form in AIDS patients previously treated with penicillin for primary or secondary disease. Treatment is with IV Pen G 12-24 million units per day for 10 days followed by 2.4 million units IM per week for three weeks. Treatment failures have been reported and steroids may be of benefit in that event. H. Kaposi's Sarcoma may present in the ear with the characteristic red-purple nodules on the auricle or in the nasopharynx. VII. SINONASAL MANIFESTATIONS OF AIDS A. Rhinosinusitis is common in AIDS patients, who are susceptible to the same organisms usually associated with sinusitis and responsive to conventional therapy. However there are also rare viral, fungal, and parasitic infection which occur. H. flu and Strep pneumoniae are the most commonly identified pathogens. Unusual isolates reported (and antibiotic treatments used) include: legionella pneumophila (erythromycin), CMV (gancyclovir), Acanthamoeba (rifampin and ketoconazole), Alternaria (surgical excision and amphotericin), and cryptococcus (amphotericin and 5- flucytosine). 1. Lucente recommends an initial trial of conventional therapy with antibiotics and decongestants in patients with no other intercurrent infections. If this does not produce cure, antral culture and lavage, followed by sinusectomy is recommended. 2. In those with intercurrent infections being treated with antimicrobials, suspect an uncommon organism and proceed to antral lavage as the first step in treatment. If sinusectomy is to be performed, arrangements should be made for specials stains and ultrastructural examination prior to surgery. B. Herpetic infections - Friedman reported that 73% of those in high risk groups that presented with zoster infections were seropositive, with an additional 15% converting later. Another newly reported entity in AIDS is the giant herpetic nasal ulcer. These ulcers may reach a diameter of up to 3 cm, begin in the vestibule, and extend onto the septum or face. Treatment of herpes infections includes acyclovir and analgesics. 3. Seborrheic dermatitis has been reported to occur in 22 - 83% of seropositive patients. It is similar to that seen elsewhere except it tends to be more severe, and may be refractory to topical steroids. C. Candidiasis is usually present in the nasopharynx as part of diffuse pharyngeal candidiasis. Treatment of choice is oral ketoconazole, because topical solutions (nystatin, clotrimazole troche) do not enter the nasopharynx. D. Nasopharyngeal lymphoid proliferation may be a presenting sign of AIDS, with complaints of nasal obstruction or otitis media. Barzan reports on 66 patients with AIDS, and finds a significant rate of nasopharyngeal lymphatic tissue hypertrophy, suggesting it may be one of the most common head and neck manifestations of AIDS. The hypertrophy was most pronounced in patients with ARC or PGL, suggesting the tissue mirrors processes occurring in other lymphatic tissue. Stern presented a series of seven patients complaining of nasal obstruction and COME. Examination confirmed nasopharyngeal lymphatic tissue hypertrophy. All patients were subsequently determined to be HIV seropositive. Some advocate removal of this tissue for symptomatic relief. E. Several authors have reported sino-nasal lymphoma in AIDS patients. Symptoms include nasal obstruction, foul smelling discharge, and unilateral facial swelling. CT shows sinus opacification and bone destruction. Unlike lymphoma in other sites, these tumors tend to remain localized rather than to disseminate. Optimal treatment is uncertain, Patients with advanced disease are usually treated with chemotherapy. Survival is poor and patients succumb to disease or intercurrent infection. Radiotherapy is an effective measure for gaining local control in the paranasal sinuses, and avoids further immunosuppression associated with chemotherapy. F. Kaposi's sarcoma has been documented in nasal skin, vestibule, nasal cavity, nasopharynx, septum, and paranasal sinus. Presenting complaints include obstruction, drainage, and epistaxis. Physical findings and treatment are as for elsewhere. VIII. ORAL CAVITY MANIFESTATIONS OF AIDS A. Fungal infections in the oral cavity are most commonly caused by candida species - reported in up to 90% of AIDS patients. Less common causes include cryptococcus and histoplasma. Oral candidiasis appears in three distinct forms. In the most common form a milky pseudomembrane forms. The membrane wipes off easily, but leaves a raw bleeding surface behind. In leukoplakic candidiasis there is a firm white membrane that cannot easily by wiped off. Atrophic candidiasis presents with erythematous patches in the buccal mucosa, hard and soft palate, or tongue. Angular cheilitis is a perioral manifestation consisting of cracking, fissuring, or ulceration at the corners of the mouth. Treatment is with topical nystatin, clotrimazole, or systemic ketoconazole depending in the extent and location of the disease. B. HIV gingivitis is an entity similar to Acute Necrotizing Ulcerative Gingivitis seen in immunocompetent patients. The patients experience pain, hyperemic gingiva, spontaneous bleeding and a rapid progression of the infection resulting in gross destruction of soft tissue and bone. Several types of bacteria have been implicated, including Streptococcus species, Staph, Klebsiella, Enterobacter, MAI, Actinomyces, and E. coli. Treatment is effective with local debridement, topical antiseptics such as povidine iodine, and a short course of metronidazole. C. Virus Infections are common in AIDS patients and the manifestations of EBV, HSV/VZV, CMV, and HPV may be seen in the oral cavity. 1. Hairy leukoplakia is an oral cavity lesion associated with EBV infection. It appears as a white,sometimes corrugated patch most commonly on the lateral tongue border. It has also been found on the floor of mouth, and elsewhere on the oropharyngeal mucosa. The lesion is usually asymptomatic, although some complain of mild discomfort and are helped by anti-fungal therapy. There are reports of remission after antiviral therapy, but long term efficacy is unknown. 2. Herpetic eruptions in healthy individuals tend to be localized small blisters that coalesce to shallow ulcers, last for 7 - 14 days, heal without scarring, and cause minimal discomfort. In contrast, the lesions of herpes simplex in AIDS patients occur throughout the mouth, especially on the palate, lips, and perioral areas. They are larger - up to 3 cm in diameter,deep, very painful, and may persist for weeks. Severe cases may be treated with acyclovir. Zoster infection in the oral cavity is rare in AIDS. 3. CMV lesions in the oral cavity are rare and only a few cases have been reported. 4. HPV is endemic in homosexual groups and HIV-infected patients. Oral manifestations include condylomata and focal epithelial hyperplasia. Recommended treatment is to have the lesions excised (by an oral surgeon). D. Kaposi's sarcoma of the oral cavity initially appears as an asymptomatic, flat or raised red-blue lesion. It may become painful if ulcerated or superinfected. Very large tumors may become lobulated. The hard palate is most commonly involved, followed by the gingiva, buccal mucosa, and soft palate. Treatment is as previously described. E. Although KS is the most common intraoral malignancy associated with AIDS, lymphomas are also found. The symptoms and appearance may be very similar to that of oral KS. F. Although not specifically at higher risk, AIDS patients may also present with squamous cancer of the oral cavity. The most common site is the tongue. G. Several other conditions have been reported to occur in AIDS patients: 1. Aphthous ulcers occur in AIDS patients and tend to be larger and more painful, sometimes interfering with speech or swallowing. They may become necrotic and require biopsy to rule out other disease processes. Topical steroids and anesthetics are recommended for symptomatic relief. 2. Thrombocytopenia in AIDS may manifest as oral ecchymoses, petechiae, and spontaneous gingival bleeding. 3. Oral mucosal hyperpigmentation in spots or stria has been described in AIDS patients. The cause is unknown, the condition benign, and no therapy required. IX. LARYNGEAL MANIFESTATIONS OF AIDS A. Epiglottitis has been noted to occur in particularly aggressive form in some cases of AIDS. While the presentation - fever, malaise, dysphagia, odynophagia and hoarseness are the same as other adult patients, certain differences were pointed out by Rothstien in a review of five cases of adult epiglottitis in AIDS patients. AIDS patients tended to present with fever, but without leukocytosis or bandemia. Physical findings were a large, pale, boggy, floppy epiglottis in all patients. Epiglottic erythema was present in less than half the patients. The infecting organisms appear to be similar to immunocompetent individuals and the treatment is the same, cefuroxime and ampicillin/chloramphenicol were effective. However, conservative treatment failed, and airway intervention was required in all patients in his small review. Tracheotomy may be required for airway management, although intubation is preferred. B. Laryngeal tuberculosis remains the most common granulomatous disease of the larynx. Studies linking TB to AIDS have estimated the incidence at up to about 30%, and extrapulomoary TB is estimated to occur in up to 55% of AIDS/TB cases. As the epidemic continues, otolaryngologists should be prepared to see more cases of laryngeal TB, which is almost always a consequence of pulmonary disease. Hoarseness, dysphagia and odynophagia remain common symptoms. Laryngoscopic findings depend on the site of the lesion, and range from ulceration to hyperemia, to edema and pale granulations. Differentiation from cancer or other granulomatous diseases is made at biopsy. A high index of suspicion should be maintained to avoid exposure of personnel to the disease, although recent evidence in non-AIDS patients suggests that the risk of infection from laryngeal TB may not be as high as previously thought. Of interest is that the clinical characterisitics of laryngeal TB may be changing. Previously studies showed the most common site of laryngeal involvement to be the posterior larynx, probably as a result of direct spread from the chest in a bed- ridden (supine) patient. With the advent of the antibiotic age, spread of TB apears to more frequently occur via hematogenous or lymphatic route. Soda reported on 19 patients (not AIDS) who were treated between 1983-88. The most common sites of involvement in these patients was the epiglottis (74%), followed by the A-E folds, arytenoids and vocal cords. C. Kaposi's Sarcoma is well documented in the larynx. When the lesions become very large or bulky, they may cause respiratory embarrassment or obstruction. Diagnosis is made on flexible fiberoptic examination. Biopsy is contraindicated due to the risk of hemorrhage. Tracheotomy may be necessary for airway management. X. SALIVARY GLAND AND CERVICAL MANIFESTATIONS OF AIDS A. Xerostomia is a common complaint in AIDS. The cause is unknown. Symptomatic treatment is indicated. B. Cystic parotid enlargement is a well documented finding in AIDS. This may occur early in the disease prior to a diagnosis of HIV infection being made. The parotid masses are typically unilateral or bilateral multicystic, nontender enlargements. CT scanning will demonstrate multiple thin walled cystic masses. Evidence from tissue studies indicates that the lesions are similar to benign lymphoepithelial lesions. The lesions more often arise in intra-parotid lymph nodes than in gland parenchyma. Surgery should be avoided due to the refractoriness of the lesion and its underlying benign nature, as well as the risk of facial nerve damage. Needle aspiration is indicated to rule out malignancy, as well as for symptomatic relief. However, the cysts will recur after needle aspiration. C. Persistent adenopathy was one of the first reported manifestations of AIDS. Lymph node architecture was discussed above. Twenty percent of AIDS patients have significant cervical adenopathy. Fine needle aspiration biopsy is advocated by Shapiro for the differential diagnosis of adenopathy. Diagnostic considerations include benign hyperplasia, lymphoma, KS, TB, toxoplasma, histoplasma, other infections or metastatic disease. Nodes greater than 2 cm, or unilateral nodes are more likely to yield diagnoses on FNA. D. Several authors have reported thyroiditis and hypothyroidism in AIDS patients subsequently determined to be the result of Pneumocystis infection. In general, pulmonary disease precedes extrapulmonary, but this is not always the case. Symptoms include an enlarged, painful thyroid, a rapidly expanding mass, and hypothyroidism. Ultrasound may show variations in echogenicity, and may be read as "hematoma". Diagnosis can be made with FNA. Treatment includes TMP/SMX and/or intravenous pentamidine. XI. PEDIATRIC CONSIDERATIONS IN AIDS A. Pathogenesis - As opposed to adult infection, in children the virus infects an immune system that is still maturing. Since B- cell development is still ongoing, infection with HIV also will result in disorders of immunoglobulin production. Children produce either too little or more commonly too much immunoglobulin, and the IG is of poor specificity and quality. As a result there is a tendency toward repeated attacks of otitis media and sinopulmonary infections similar to that seen in hereditary defects of immunoglobulin production. B. Currently, most children who are HIV positive acquire the virus from their mother. The rate of transmission is probably around 50% but may be as high as 75%. There is limited knowledge of trans- placental infection, however the virus has been isolated from cord blood in 15 week abortuses, and there are reports of children born via caesarean who develop AIDS. In addition, there is a subset of patients whose disease progresses rapidly from birth who were probably infected early in their pregnancy. Children who show symptoms later in their lives were probably infected at birth. There are also reports of a seronegative mother transfused at birthing who subsequently transmitted the virus in breast milk. C. Testing - Because of the large volume of transmitted maternal antibodies, HIV testing in children under 15 months old is not practical. Further, because of impaired B-cell function many children will not mount an IgG response sufficient to be measured. Thus the definitive test in this age group is isolation of the virus from blood and body fluids. The polymerase chain reaction amplifies short sequences of nucleic acids and may be useful for detecting proviral DNA, making it a potential screening test in at- risk children. D. Infections in children are similar to adults, plus children are at risk further due to their impaired humoral immunity. Of particular importance is a tendency of pediatric AIDS patients to overwhelming gram negative sepsis, especially from Pseudomonas. The HIV associated neoplasms common in adults are rare in children. E. A dysmorphic syndrome has been associated with intrauterine HIV infection. The syndrome consists of microcephaly, a short nasal bridge, short nose with flattened columella, obliquity of the eyes, hypertelorism and a block-like forehead. Some argue that these features are more a reflection of an overall insult to a first trimester fetus from ingested toxins, alcohol, drugs, or infections. XII. PATIENT CARE CONSIDERATIONS IN AIDS A. The risk of transmission of HIV from patient to surgeon or surgeon to patient appears to be quite low. While about 5% of AIDS and HIV infection cases in the United States occur in health care workers, there have to date been only 28 proven episodes of seroconversion following exposure to HIV infected patients. None of these has been in surgeons, and none occurred in the operating room. In one large study, seroconversion occurred in 6 of 1538 health care workers suffering 1607 needlestick injuries. Taken together, the many epidemiological studies place the risk of seroconversion at about 0.5% per parenteral exposure. The risk is probably related to the mode of exposure as well as to the size of the inoculum. There is reported transmission of hepatitis B without HIV, supporting the perceived decreased transmissibility of HIV in comparison. B. The touted figures on the difficulty of contracting HIV are of small comfort to surgeons who are repeatedly asked by our Medicine colleagues to perform operative procedures on HIV positive and AIDS patients. The Surgical Infection Society, in a recent Archives of Surgery article, recommend the following combination of procedures be followed to minimize risk to health care workers from HIV and other deadly blood born diseases: 1. Only the minimum number of people required should participate in the case. 2. Inexperienced, non-essential and pregnant workers should not participate. 3. Persons with open wounds or sores should not participate if the wounds are in a location likely to be soiled. 4. Disposable plastic aprons are advised if more than minimal bleeding is expected. 5. Disposable scrubs should be worn. 6. All personnel should wear eye protection with side shields. 7. Soiled masks should be changed immediately. 8. Underclothes or shoes contaminated should be soaked in chlorine bleach. Rubber boots are preferred. 9. Care should be taken to avoid needle sticks. This includes proper handling of suture as well as not recapping needles. 10. Scalpel use should be kept at a minimum. Cautery is recommended for incisions, as well as dissection. 11. Sharps to be handled only by the surgeon and scrub nurse. 12. No one should remove instruments from the scrub tray. 13. Pathology should be notified in advance of infectious specimens, and all infectious specimens labeled. 14. All personnel should wash hands thoroughly after the case. 15. If there was possibility of skin contamination, a warm shower with antimicrobial soap is indicated immediately post-op. 16. Dirty procedures should be scheduled at the end of the day to promote cleaning. C. In addition to the above, T.M. Davidson recommends: 1. HIV testing for all patients undergoing major surgery. 2. Availability of AZT in the OR for those desiring immediate prophylaxis. 3. Testing and immunization of all OR personnel for Hep B. 4. All OR personnel to wear eye protection, with full face shields required when procedures such as jet irrigation are undertaken. 5. Double gloving by the entire operating team for all cases. Other studies have shown the risk of single glove failure as indicated by soilage of the hands may be as high as 50%. Double gloving reduces the risk to about 7%. He further recognizes that there are two categories of patients - those considered to be high risk or known to be HIV or Hep B positive, and those felt to be low risk, and recommends that the inexperienced (i.e. medical students) not perform venipuncture, or assist or perform surgery on HIV and Hep B patients. Pollard in reply questions the need to develop special precautions for high risk patients. He correctly points out that the overwhelming risk to health care workers is needle stick and sharp injuries, and suggests that the major effort should be addressed to decreasing risk from this type of exposure (a copy of a recent letter to JAMA restating safe suture techniques is attached as a timely reminder). However, some might (and have) contend his commentary reflects a lack of appreciation of operating procedure and techniques all too common in non-surgeons who are attempting to dictate what precautions are appropriate for surgeons to follow. D. Post-Exposure Prophylaxis - A decision analysis concerning post exposure prophylaxis with AZT concluded that even a small benefit would outweigh the risks associated with the drug. However further data, including several cases in which AZT was begun immediately and seroconversion occurred, suggest a limited utility. The decision to begin AZT prophylaxis is therefore based on the individual circumstances, including sero-status of the patient, method of exposure and inoculum size. Some surgeons report keeping AZT in their lockers to avoid delay while the patients sero-status is determined. Policy at UTMB is not to routinely prophylaxis, although the policy may be reevaluated in the future. ------------------------------------------------------------------------------- BIBLIOGRAPHY 1. Barzan L, et al. Nasopharyngeal Lymphatic Tissue in Patients Infected with HIV. Arch Otolaryngol Head Neck Surg 1990 116(8):928-31. 2. Brahim JS, Roberts MW. Oral Manifestations of HIV Infection. ENT Journal 19090 69(7):464-474. 3. Burget GC, et al. HIV Infected Surgeons (letter). JAMA 1992 267(6):803. 4. CDC. Revision of the Case definition of AIDS for Surveillance Purposes. MMWR 1987 136(suppl):3s-15s. 5. CDC. The Second 100,000 Cases of AIDS. MMWR 1992 41(2):28-29. 6. Chanock SJ, McIntosh K. Pediatric Infection with the HIV - Issues for the Otolaryngologist. Otolaryngol Clinics North Am 1989 22(3):637-60. 7. Chow JH, et al. Head and Neck Manifestations of the Aquired Immunodeficiency Syndrome in Children. ENT Journal 1990 69(6): 416-23. 8. Corey JP, Seligman I. Otolaryngologic Problems in the Immunocompromised Patient - An Evolving Natural History. Otolaryngol Head Neck Surg 1991 104(2):196-203. 9. Davidson BJ, et al. Lymphadenopathy in the HIV-seropositive Patient. ENT Journal 1990 69(7):478-485. 10. Davidson TM, and Stabile B. AIDS Precautions for Otolaryngology - Head and Neck Surgery. Arch Otolaryngol Head Neck Surg 1991 117(12):1343-4. 11. Davis JM, et al. The Surgical Infection Society's Policy on HIV and Hepatitis B and C Infection. Arch Surg 1992 127(2):218- 221. 12. Drucker DJ, et al. Thyroiditis as the Presenting Manifestation of Disseminated Extrapulmonary Pneumocystis Carinii Infection. J Clin Endocrinol Metab 1990 71(6):1663-65. 13. Finfer MD, et al. Cystic Parotid Lesions in Patients At Risk for AIDS. Arch Otolaryngol Head Neck Surg 1988 114(11):1290-94. 14. Goldstien J, et al. Lymphoma of the Maxillary Sinus in a Patient Infected With HIV-1. Head Neck 1991 13(4):355-58. 15. Kohan D, et al. Otologic Disease in AIDS - CT Correlation. Laryngoscope 1990 100(12):1326-30. 16. Kwartler JA, et al. Sudden Hearing Loss Due to AIDS Related Cryptococcal Maningitis - A temporal Bone Study. Otolaryngol Head Neck Surg 1991 104(2):265-269. 17. Levy FE, Tansek KM. AIDS-Associated Kaposi's Sarcoma of the Larynx. ENT Journal 1990 69(3):177-184. 18. Lucente FE. Otolaryngologic Aspect of the Acquired Immunodeficiency Syndrome. Med Clin North Am 1991 75(6):1389-98. 19. Meiteles LZ, Lucente FE. Sinus and Nasal Manifestations of the Acquired Immunodeficency Syndrome. ENT Journal. 1990 69(7):454-59. 20. Mishell JH, Applebaum EL. Ramsay Hunt Syndrome in a Patient with HIV Infection. Otolaryngol Head Neck Surg 1990 102(2):177-9. 21. Morris MS, Prasad S. Otologic Disease in the Acquired Immunodeficiency Syndrome. ENT Journal 1990 69(7):451-3. 22. Pollard RB. Analysis and Perspective from the Infectious Disease Department. Arch Otolaryngol Head Neck Surg 1992 117(1):19. 23. Quebbeman EJ, et al. Double Gloving. Arch Surg 1992 127(2):213-217. 24. Ragni MV, et al. Pneumocystis Carinii Infection Presenting as Necrotizing Thyroiditis and Hypothyroidism. Am J Clin Pathol 1991 95(4):489-93. 25. Rarey KE. Otologic Pathophysiology in Patients with HIV. Am J Otol 1990 11(6):366-69. 26. Rothstein SG, et al. Epiglottitis in AIDS Patients. Laryngoscope 1989 99(4):389-92. 27. Sandler ED, et al. Pneumocystis carinii Otitis Media in AIDS - Case Report and Review of Literature. Otolaryngol Head Neck Surg 1990 103(5):817-21. 28. Shapiro AL, Pincus RL. Fine Needle Aspiration of Diffuse Cervical Adenopathy in Patient With the Acquired Immunodeficiency Syndrome. Otolaryngol Head Neck Surg 1991 105(3):419-21. 29. Soda A, et al. Tuberculosis of the Larynx. Clinical Aspects of 19 Patients. Laryngoscope 1989 99(11):1147-50. 30. Sperling NM, Pi-Tang Lin. Parotid Disease Associated with HIV Infection. ENT Journal 1990 69(7):475-477 31. Stafford ND, et al. Kaposi's Sarcoma of the Head and Neck in Patients with AIDS. J Laryngol Otol 1989 103(4):379-82. 32. Stern JC, et al. Benign Nasopharyngeal Masses and HIV Infection. Arch Otolarngol Head Neck Surg 1990 116(2):206-8. 33. Wenig BM, etal. Pathologic Manifestations of AIDS in the Head and Neck. ENT journal 1990 69(6):406-415. 34. Weiss SH. HIV infection and the Health Care Worker. Med Clin North America 1992 76(1):269-280. ------------------------------------------------------------------------------ TEST QUESTIONS - The following test questions are intended to provide proof to accrediting agencies that you have read and understood the entire Grand Rounds element. Your answers should be based on the text of the Grand Rounds element. Answers should be sent by e-mail addressed to fbquinn@utmb.edu. Answers can be sent by U.S Postal Service mail, using a plain sheet of paper on which the Grand Rounds element and the subscriber are fully identified. Correct answers will be transmitted to the subscriber via e-mail on request. Comments and alternative points of view should be expressed at the end of the list of the subscriber's answers. E-mail answErs can be submitted thus: Otitis media 1b, 2c, 3b, 4a, 5c, 6b, 7d, 8c, 9a, 10a yes, yes, yes, no, yes, ?, yes, ?, 50 cents The University of Texas Medical Branch (UTMB) is accredited by the Accreditation Council For Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. UTME designates this continuing medical education activity for 1 credit hour in Category 1 of the Physicians's Recognition Award of the American Medical Association. 1. Aproximately what percentage of AIDS patients manifest disease in the head and neck at some stage of their disease? a. 10% b. 33% c. 67% d. 99% 2. Which opportunistic pathogen (the one most commonly associated with AIDS) can infect the external ear and the thyroid in addition to the lung? a. pneumocystis carinii b. toxoplasma gondii c. candida albicans d. mycobact erium tuberculosis 3. Which of the following is a common complaint in AIDS? a. hearing loss b. otalgia c. otorrhea d. vertigo e. all of the above 4. All of the following viruses are commonly seen in the head and neck of AIDS patients except: a. cytomegalovirus b. Epstein-Barr virus c. herpesvirus d. papilloma virus e. papova virus 5. The most important fungal infection in HIV+ patients, the presence of which often heralds progression to AIDS is: a. cryptococcus b. aspergillus c. candida d. histoplasma e. coccidiodes 6. What percentage of HIV+ patients develop some type of lymphoma? a. 1% b. 10% c. 30% d. 50% e. 70% 7. Predominant etiologic agents in acute otitis media in AIDS patients include all of the folowing except: a. B. cat arrhalis b. P. carinii c. S. pneumonia d. H. influenza 8. Sensorineural hearing loss in AIDS may commonly be due to all of the following except: a. HIV infection b. bacterial infections c. viral infections d. ototoxic medications e. herbal home therapies 9. Treatment of choice for nasopharyngeal candidiasis is: a. clotrimazole troches b. nystatin suspension c. oral ketoconazole d. i.v. acyclovir 10. Oral hairy leukoplakia is associated with which viral infection? a. CMV b. EBV c. HSV d. VZV In order for the sponsors of this CME activity to monitor its usefulness and appropriateness to subscribers, we ask that you supply answers to the following questions concerning the accompanying Grand Rounds Online CME segment: 1. Was the presentation organized in an acceptable manner? yes no opinion no 2. Was the material adequate to your continuing education needs with respect to content? yes no opinion no 3. Was the material appropriate to your clinical practice needs? yes no opinion no 4. Did you feel that the discussants' remarks were responsive to the issues presented in the body of the Grand Rounds segment? yes no opinion no 5. Do you consider the presentation to be timely with regard to current information available in both the lay press and the professional literature? yes no opinion no 6. Are the questions submitted with the Grand Rounds element meaningful in that they stimulate thought and perhaps further inquiry? yes no opinion no 7. Is the method of submitting the subscriber's answers to these questions expeditious and convenient? yes no opinion no 8. Would you recommend this method of completing the general requirment for Continuing Education Activity to your colleagues? yes no opinion no 10. How much money (U.S. dollars) would you be willing to pay for each award of 10 or more CME Category I credits earned through this type of online CME activity? $100 $50 $25 $12.50 $6.25 $3.00 $1.50 $0.75 $0.35 $0.15 Please submit any comments, criticisms and suggestions which you may have in the space below. They will be given thoughtful consideration, especially if they are favorable comments, gentle criticisms, or constructive suggestions. 8-) /s/ The Editor. Francis B. Quinn, Jr., M.D. University of Texas Medical Branch Dept. of Otolaryngology Galveston, TX 77555-0521 Internet addresses: 409-772-2706, 772-2701 fbquinn@UTMB.edu 409-772-1715 FAX fbquinn@phil.utmb.edu ----------------------------------END------------------------------------------