The first AIDS case was reported in June 1981. By December 31, 1996, over 570,000 cases of full blown AIDS had been reported, nearly 70,000 new cases diagnosed in 1996 alone. The prevalence of AIDS in 1996 was 223,000 according to The Center for Disease Control. These figures represent an increase in the prevalence and decrease in the incidence of AIDS from previous years. The CDC estimates that in addition to the reported cases, an estimated 1,500,000 Americans are infected with HIV. AIDS will develop in most - if not all. A recent survey at the Johns Hopkins University Emergency Room found 5% of all patients over a 6 week period to be HIV positive, with 13% of all penetrating trauma victims testing HIV positive.
Homosexual and bisexual males continue to comprise the majority of AIDS cases (44%), followed by IV drug users (26%). Other at risk groups include the female sexual partners of IV drug abusers, hemophiliacs, and children of HIV positive mothers. The rate of infection in women continues to rise, with 20% of the cases in 1996 occurring in females. More than half of these cases were linked to heterosexual transmission. Blacks and Hispanic males continue to be disproportionately infected - 38% and 19% of all cases respectively.
AIDS is now the number one cause of death in individuals 25-44 years old. The rate of spread of AIDS in homosexuals has declined, as the rate of heterosexual transmission has accelerated. In some larger cities, 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). 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 units obtained from individuals early in their infection who are not yet seropositive.
Fifty percent of males infected with HIV progress to AIDS within 9 years of seroconversion. Progression is more rapid in Children. 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. Zidovudine (AZT) appears to slow the progression of disease and increase the symptom-free period. Many studies have shown that the combination of AZT with other newer agents have increased the absolute survival of these patients if started early in the disease.
For purposes of reporting AIDS cases, the CDC defines the illness as being present in HIV infected persons with a CD-4 count of < 200 T Lymphocytes/?l, a CD-4 percentage of total lymphocytes of <14%, or having three of the designated “indicator” diseases. Specific diseases are notable complications of the immunocompromised status of infected individuals and include certain bacterial infections in children, opportunistic infections that take advantage of decreased T-cell function, B-cell lymphomas, and AIDS encephalopathy.
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. 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 of the host genome to incorporate into the host genome allows the virus to cause disease with a long latency period.
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. 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. T-helper counts between 200 and 500/mm3 are associated with tuberculosis, hairy leukoplakia and Kaposi's Sarcoma. The CDC currently recommends initiation of AZT therapy in this stage. Counts less than 200 increase risk of Pneumocystis infection and TMP-SMX prophylaxis should be considered. As is true with many other viruses, HIV also produces a primary neuropathy, cardiomyopathy, dementia, wasting syndrome, as well as other disorders.
At least 85% of AIDS patients will have head and neck manifestations, and it is estimated that 40 - 51% of all patients with AIDS initially present with head and neck manifestations. It is therefore essential that the practicing Otolaryngologist have a good grasp of the common presentations, diagnosis, and treatment of AIDS related illness in the head and neck.
Viral infections are commonly seen in the head and neck in AIDS patients. The DNA viruses are most commonly identified - cytomegalovirus (CMV), Herpesvirus (HSV), Varicella-Zoster virus (VZV), Epstein-Barr virus (EBV), and papilloma virus (HPV). 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 or as CMV retinitis. The characteristic histology shows ulceration, necrosis, and cytomegaly, with intra-nuclear or intra- cytoplasmic inclusions. Immunofluorescence can be used to confirm the infection. Ganciclovir is the drug of choice. HSV is a frequent cause of mucocutaneous disease in AIDS. In the general population HSV infection tends to cause localized shallow ulcers. In the immunocompromised it can cause large deep ulcerations which may be disseminated. Histology shows acantholysis and degeneration of epithelial cells with intranuclear inclusions. Multinucleated cells are common. HSV may arise in dermatomal distribution (shingles) or as Ramsay Hunt syndrome. Histology is indistinguishable from VZV. Herpesvirus infections may be treated with acyclovir. 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 Burkitt lymphoma. The association of EBV with nasopharyngeal carcinoma seen in non-immunocompromised patients has not been demonstrated in AIDS. HPV is associated with condyloma and epithelial hyperplasia, and seems to play a role in the development of epithelial malignancy.
Mycobacterial infections are seen in high frequency in AIDS. M. avian intracellulare is the most common species, followed by M. tuberculosis. Histology shows replacement of normal cellular architecture with confluent caseating granulomas. Giant cells are seen, and acid fast stains 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 now frequently encountered. 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, and may not respond to conventional antisyphilis therapy.
Candida causes the most common fungal infection in the head and neck in HIV positive patients, and its presence often heralds 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 pseudomembranous scrapable white plaque. An atrophic form with mucosal erythremais also common and may be difficult to distinguish from telangiectasia, erythema multiforme, and erythroplakia. A third, hyperplastic form is less common, but may be confused with hairy leukoplakia Biopsy will confirm the diagnosis. Budding yeast and pseudohypha are found on histologic section. 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. 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. Amphotericin-B is necessary for induction therapy, followed by lifelong maintenance therapy with an imidazole. 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 by or histologic evaluation, and amphotericin is the preferred therapy. Numerous other mycotic infections occur with varying incidence, including aspergillosis, dermatophytoses, and others.
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. 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 Aids Related Complex (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 an invariable lack of germinal centers, with histiocytosis, reduction of lymphocytes and often increased plasma cells. This pattern has been associated with rapid progression of AIDS. 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 (Non-Hodgkins), with a predisposition for extranodal sites - e.g. bone marrow, skin, liver, GI tract and CNS. Many AIDS related lymphomas present as neck masses.
In AIDS, as opposed to classic or endemic Kaposi's Sarcoma , KS tends to be more aggressive, characteristically progressive, but rarely fatal. Epidemic KS in the head and neck may present as mucocutaneous or nodular 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 is most often cosmetic, and depends upon the amount of disease, and the patients overall immune status. It ranges from no treatment, to local treatment with excision (CO2 laser useful) in those with one or two lesions and indolent disease, to multiagent chemotherapy (vinblastine, doxorubicin) and XRT in more advanced disease. Alpha Interferon has also been used with limited success.
Otitis externa in AIDS tends to be similar to infection found in non- immunocompromised individuals. It is typically caused by Pseudomonas aeruginosa, and less commonly by Proteus or Aspergillus species. 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, although Lucente has had several patients with severe persistent fungal OE which has required intensive local and systemic therapy. Acute Otitis Media in AIDS tends to parallel AOM in the population at large, with S. pneum, H. flu and B. catarrhalis predominating. There is evidence of an increased attack rate of AOM in AIDS patients during the early stages of the disease, when nasopharyngeal lymphatic tissue is hypertrophied. Infection responds to standard antibiotic therapy, and failure to improve should prompt tympanocentesis for culture 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. Chronic Otitis Media has not 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, otorrhea, 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. Mastoiditis, cholesteatoma, and other suppurative complications of otitis have not been shown to occur more frequently in the AIDS population.
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.
Sensorineural hearing loss is common in AIDS due to infection with HIV itself, infection with other organisms, malignancy, and the administration of ototoxic medications (antifungals, aminoglycosides, immunomodulators). 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. Almost half of all AIDS patients suffer from SNHL. One post-mortem study showed myelopathy-like 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. In general, high frequencies are more affected, and ABR demonstrates prolonged wave V latencies, implying central etiology. Otosyphilis and neurosyphilis are more severe diseases in HIV infected individuals and follow the primary infection at an accelerated rate, as well as speed the progression of AIDS.
Otosyphilis occurs in the tertiary stage of the disease with complaints similar to hydrops - uni- or bi-lateral SNHL which may progress rapidly, and hydropic labyrinthine 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 at any stage of HIV infection, 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. Steroid therapy is hazardous in the immunocompromised AIDS patient and is controversial.
The prevalence of VII nerve palsy seems to be higher in patients with HIV infection. Bell's palsy is the most common diagnosis in HIV patients. Primary infection or reactivation of Herpes infection in the HIV population (with dysfunctional cellular immunity) may explain the relative increased incidence. It may be the presenting sign in a previously undiagnosed HIV patient. The course of the disease and treatment is the same as in the general population, with the exception that Cortic steroid therapy must be closely monitored. Herpes Zoster oticus, or Ramsey Hunt Syndrome, associated with facial nerve paralysis is more common in the AIDS population. The treatment is high dose acyclovir, and steroids are obviously controversial. Any AIDS patient with a cranial neuropathy must have a complete neurologic evaluation because frequent multiple central nervous system complications are common.
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 > 3 cm, begin in the vestibule, and extend onto the septum or face. Treatment of herpes infections includes acyclovir and analgesics. 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. Candidiasis is often 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.
Nasopharyngeal lymphoid proliferation may be a presenting sign of AIDS, with complaints of nasal obstruction or otitis media. This most often occurs early in the disease, with subsequent regression in advanced AIDS. 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.
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 concurrent infection. Radiotherapy is an effective measure for gaining local control in the paranasal sinuses, and avoids further immunosuppression associated with chemotherapy.
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 the same as in other head neck sites.
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 povidone iodine, and a short course of metronidazole.
Virus Infections are common in AIDS patients and the manifestations of EBV, HSV, and HPV may be seen in the oral cavity. Hairy leukoplakia is an oral cavity lesion associated with EBV infection. It appears as a white, sometimes corrugated patch most commonly found 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 patients 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. Herpetic eruptions in healthy individuals tend to be localized small blisters that coalesce into 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. 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. Zoster infection in the oral cavity is rare in AIDS.
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. 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. 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.
Several other conditions have been reported to occur in AIDS patients: 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. Thrombocytopenia in AIDS may manifest as oral ecchymoses, petechiae, and spontaneous gingival bleeding. Oral mucosal hyperpigmentation in spots or stria has been described in AIDS patients. Most frequently the cause is AZT hyperpigmentation, some cases have been seen in patients prior to AZT induction. The etiology is unknown.
Laryngeal tuberculosis remains the most common granulomatous disease of the larynx. Studies linking TB to AIDS have estimated the incidence at up to about 50%, and extrapulmonary 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, odynophagia, referred otalgia, cough, and stridor remain common symptoms. Laryngoscopic findings depend on the site of the lesion, and range from ulceration and 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 characteristics 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 appears to more frequently occur via hematogenous or lymphatic route. The vocal folds are the most common site affected (50 - 70% of cases) closely followed by the ventricular bands.
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. CO2 laser, chemotherapy and radiation therapy are the recommended treatment for obstructive cases.
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. Tetracycline sclerosis after aspiration has shown moderate success in several trials.
Persistent generalized adenopathy was one of the first reported manifestations of AIDS. Lymph node architecture was discussed above. Up to 70% 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 and unilateral nodes are more likely to yield diagnoses on FNA, but nodes >3cm should be surgically excised for evaluation.
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.
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.
Infections in children are similar to adults, plus children are at further risk due to their impaired humoral immunity. Of particular importance is a tendency of pediatric AIDS patients to develop overwhelming gram negative sepsis, especially from Pseudomonas. The HIV associated neoplasms common in adults are rare in children. 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.
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 patients. A summary of the recommendations for surgical precautions from Kantu, et al, follows:
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 primarily on method of exposure and size of the inoculum. Some surgeons report keeping AZT in their lockers to avoid delay while the patients sero-status is determined. Policy at UTMB is to leave the decision for prophylaxis up to the individual involved.