More than 70% percent of patients with Human Immunodeficiency Virus (HIV) infection will at some stage present with a Head and Neck or Ear, Nose and Throat manifestation, many of them with multiple lesions (1,2,3,4). There are no Acquired Immune Deficiency Syndrome (AIDS) – defining conditions specific to the Head and Neck, but many AIDS-defining lesions do manifest in the Head and Neck and a wide variety of problems associated with HIV infection are also commonly seen. In addition, there are a number of lesions which if found are indications for offering HIV testing to a patient. A thorough understanding of these HIV related problems is essential to facilitate early diagnosis as well as comprehensive and appropriate care of the HIV-infected person. This chapter discusses the common manifestations of HIV disease in the head and neck region. For clarity, the topic is approached by considering the nature of pathologies (cutaneous and mucosal lesions, inflammatory and infective conditions, neoplasms, and neurologic damage) and the sites affected (skin and face, nose and paranasal sinuses, external, middle, inner ear and skull base, oral cavity, salivary glands, pharynx, larynx, upper oesophagus, and the neck). It is to be noted, however, that there is a considerable overlapping of categories by several of the lesions. Cutaneous and Mucosal Lesions Cutaneous disorders are very commonly encountered in HIV-infected patients. Up to 90% of patients suffer from skin diseases during their course of illness and skin disorders may be the first manifestation of HIV disease (5). The spectrum of these disorders is wide and includesskin infections, inflammatory conditions, cutaneous malignancy and miscellaneous manifestations including drug reactions. In theory, any of the skin manifestations may be present in the head and neck, but the actual manifestation is determined by the immunologic state,concurrent use of medication and the pattern of infections in the locality, and the number and degree of manifestations worsens with worsening immunity (5,6,7). Thus, while head and neck cutaneous manifestations can be seen even early, the occurrence and number of lesions increase with advancing disease. Common head and neck cutaneous lesions include candidiasis, recurrent aphthous ulcers, Kaposi’s sarcoma, oral hairy leucoplakia, molluscum contagiosum, herpes simplex, herpes zoster (Shingles), psoriasis, seborrheic dermatitis and mucosal dryness from salivary gland disease as shown in table 1. The management of skin disease is important for cosmetic reasons, self-esteem and quality of life issues. Even minor conditions should not be overlooked and the dermatologist is in the best position to manage these lesions especially those that are refractory to normal treatment Inflammatory and infective conditions As expected in immunocompromised states, infection is common in the Head and Neck and they could be life-threatening. The entire spectrum of infective diseases can he found: viral (HSV 1, Varicella Zoster, Cytomegalovirus), bacterial (usually caused by expected organisms for variousinfections, but tuberculous and non-tuberculous mycobacteria are common), fungal (Candidiasis, Aspergillosis, Cryptococcosis Histoplasmosis Coccidioidomycosis) and parasitic (Toxoplasma). Usually, infections in the various tissues are caused by the pathogens expected in patients with a normal immune system, though they tend to occur more frequently and run a more severe course. Treated promptly, the majority of patients respond to standard medical management. Unusual organisms are however found in the later stages ofdisease as are unusual opportunistic infections such as those caused by mycobacteria, fungi and parasites. Neoplasms Kaposi’s sarcoma and non-Hodgkin’s lymphoma are famously associated with HIV disease. Kaposi’s Sarcoma is an idiopathic multiple sarcoma and is the commonest tumour in HIV infection (1,8). It is an AIDS-defining cancer and can manifest even early in the course of the disease. It may manifest as multiple synchronous tumours in the body and there may be more than one tumour arising from the skin or mucosal surfaces of the head and neck. Non-Hodgkin’s lymphoma usually appears late in the course of HIV disease and presents with fever, night sweats and weight loss associated with a mass. Squamous cell carcinomas have also been reported found arising from the epithelia in the head and neck of HIV patients. The incidence is not clear, and association with HIV controversial. However, such tumours have been found to be very aggressive despite highly active antiretroviral therapy and need to be promptly and aggressively treated (9). Neurologic damage Head and Neck neurologic damage is most commonly in the form of a seventh cranial nerve palsy (1). Damage to the facial nerve is more common in HIV-infected patients than in immunocompetent individuals (10). It can be a manifestation of central nervous system disease in the so-called Facial Nerve/ Central Nervous System Facial-Paralysis Syndrome or it may be an idiopathic (or Bell’s palsy) believed to be due to an infection of the nerve in the facial canal by the herpes simplex virus (.1,10). Central nervous system disease causing an upper motor neuron facial nerve palsy has been reported from CNS toxoplasmosis, HIV encephalitis and CNS lymphoma (1). The palsy may be unilateral or bilateral. CNS disease must be promptly treated, but even so, the prognosis for full recovery of nerve function is poor. In cases of Bell’s palsy, the paralysis is a lower motor neuron type and prompt treatment with a course of oral prednisolone and acyclovir commenced within the first two weeks of onset (the earlier, the better) is the standard treatment and most patients recover full function within three to four months (11,12) Skin and Face: Fungal infections Fungal infection predominates due to its opportunistic nature. It is the most common skin disorder found among HIV positive patients and occurs very frequently on the face presenting most commonly as Dermatophytosis and Candidiasis. Other common skin fungal infections include Aspergillosis, Penicilliosis and Cryptococcosis (5). Mostly the fungal infections run a chronic indolent course and can be managed with routine topical and systemic antifungals. However, there is an acute invasive and life-threatening form usually involving aspergillosis which is rapidly progressive and may necrose the face and facial bones within a very short period. Prompt recognition and treatment are essential for survival in acute invasive aspergillosis. Viral infections Common viral infections include herpes simplex, herpes zoster, molluscum contagiosum and facial warts. Herpes simplex is usually due to the reactivation of latent infection with Herpes Simplex Virus and usually manifests as oro-labial vesicles, and rarely folliculitis or (13) verrucous lesions and ulcers in advanced HIV disease. Herpes Zoster is a recrudescence of varicella zoster infection. It is common in early stages of HIV infection and may be the first clue of infection. Multi-dermatomal Herpes Zoster, common in advanced HIV disease can also occur in the head and neck along the courses of more than one cranial nerve (13). Molluscum contagiosum is caused by pox virus that selectively infects human epidermal cells and presents with pearly papules with central umbilication, or atypically with lesions such as giant mollusca in advanced HIV disease (5). Infection with Human Papilloma Virus also frequently occurs and manifests as warts. Antiviral drugs, usually oral (but also systemic in disseminated disease) are used to treat herpes simplex and herpes zoster. Treatment options in Molluscum contagiosum and warts include podophyllotoxin, imiquimod, CO2 laser, cryotherapy, curettage, excision and topical tretinoin and cidofovir (5,13,14). In general, treatment ofthese viral lesions is more effective while the HIV patient is on HAART. Bacterial infections Bacterial infections on the face are also common in HIV-infected patients. Acute infections are most commonly caused by Staphylococcus aureus and can manifest as cellulitis, folliculitis, facial abscess, nasal vestibulitis and other skin and soft tissue infections. Acute facial sepsis can have severe manifestations, progress rapidly and lead to systemic sepsis or intracranial spread of infection in these patients. They should be treated promptly according to local antibiotic policies and sensitivity where applicable with or without surgical intervention. Chronic infections caused by tuberculosis, atypical mycobacteria and syphilis are also found. A high index of suspicion is always needed to direct appropriate assessment and facilitate early diagnosis and prompt treatment in these chronic infections. Other Skin Lesions Other skin lesions include seborrhoiec dermatitis and psoriasis. Seborrhoeic dermatitis presents with a rash and is said to be common in advanced disease. It can occur anywhere in the head and neck but is particularly common in the post-auricular, nasal, and malar regions and the malar rash can resemble the butterfly pattern of systemic lupus erythematosus (14). Treatment of seborrhoiec dermatitis is usually with topical corticosteroids although eradication of the rash is usually challenging. Psoriasis has been said to often occur as the first clinical manifestation of HIV disease although it is often also seen in advanced disease. The treatment of psoriasis is equally very challenging and may involve topical treatment, phototherapy and systemic treatment (15). Kaposi’s sarcoma, manifesting as pink, blue or brown lesions are also commonly found and should not be confusedwith benign skin lesions. Nose and paranasal sinuses Nasal and paranasal sinus manifestations are known to be among the most common presentations of HIV disease (1) and estimates from prospective studies have described a 30 to 68% prevalence of sinusitis (1,16,17,18,19).Cutaneous lesions similar to those found on the face are also well documented in the sino-nasal region (16). Other problems in this region include nasal obstruction (36) from a wide range of problems that are also commonly found associated with HIV. These include adenoid hypertrophy, allergic rhinitis (18), acute and chronic sinusitis, and sino-nasal or nasopharyngeal neoplasms (20). Kaposi’s Sarcoma and Non-Hodgkin’s lymphoma are both also known to occur in this region in HIV patients. As a result of many of these lesions, eustachian tube obstruction and eustachian tube dysfunction commonly supervene, associated with sequelae of middle ear effusion and recurrent middle ear infections. Thus, HIV positive patients who present with nasal obstruction need to be thoroughly evaluated as the differential diagnosis ranges from benign problems like allergic rhinitis to sinister malignancies. Assessment should include evaluation of hidden areas of the upperaero-digestive tract with a flexible nasal endoscopy, appropriate radiological investigations such as CT or MRI and biopsies of any masses or asymmetrically enlarged nasopharyngeal lymphoid tissue found. The external ear The external ear which includes the pinna and the external auditory canal can be affected by the same spectrum of pathology as the skin since it is lined by skin. However, the peculiarities of the anatomy may produce additional symptomatology. For example, patients with seborrheic dermatitis may present with itchy ears and scaly ear discharge. A conductive hearing loss may also supervene as debris continues to accumulate. In the same way, neoplasms like Kaposi’s sarcoma may cause hearing loss by obstructing the canal or eroding into the middle ear, but it can also invade the labyrinth and lead to vestibular symptoms. Also, herpes zoster (affecting the geniculate ganglion of the facial nerve, called herpes zoster oticus or Ramsay Hunt syndrome) may present with a lower motor neuron facial nerve palsy, deafness, vertigo and pain. Infection of the external ear may present as pinna cellulitis, bacterial otitis externa or a fungal infection (Otomycosis). The organisms implicated are as expected for the immunocompetent individual. There is, however, an increasing incidence of unusual infections with organisms like Mycobacterium tuberculosis and Pneumocystis carinii. When otitis externa does not respond to standard antibiotic regimens, necrotizing otitis externa, also known as “malignant otitis externa” because of its invasive nature should be suspected. This is a severe manifestation of otitis externa usually found in immunocompromised individuals where the infection spreads to the skull base leading to skull base osteomyelitis and lower cranial nerve palsies usually initially affecting the facial nerve. This diagnosis can be confirmed using computed tomography (CT) scans of the temporal bone. The most common pathogen involved is Pseudomonas, but fungi such as Aspergillus may also be responsible (22). The middle ear In the middle ear, the most common otologic problems reported in HIV-infected patients are middle ear effusion (serous otitis media) and recurrent acute otitis media. The tendency to develop these conditions is high when there is nasal obstruction, recurrent sinusitis, allergies tumours and subsequent eustachian tube obstruction or dysfunction. The usual organisms found in immunocompetentpatients, Streptococcus pneumoniae and Haemophilus. influenza, predominate but mycobacteria and fungi have also been isolated in HIV patients. Ear infections are especially common in paediatric patients with HIV disease due to a combination of the risk posed by the normal paediatric susceptibility to middle ear infection (22) as a result of the eustachian tube anatomy in children and depressed cell-mediated immunity. HIV patients are also at risk of severe morbidity and mortality from complications of otitis media including mastoiditis, labyrinthitis, neck abscesses, venous sinus thrombosis and intracranial spread of infection. Prompt broad-spectrum anti-infective treatment and close surveillance for as well as prompt management of complications are mandatory in these patients. The inner ear Sensorineural hearing loss and vertigo can occur in the HIV-infected patient (23,24). Sensorineural hearing loss can be unilateral or bilateral. It may be due to direct CNS infection by the HIV virus or damage of the cochlear nerve by the neurotropic HIV virus. It may also be due to other CNS infections, for example, syphilis and cryptococcal meningitis, neoplasms or ototoxic medications. A thorough workup is necessary to detect the cause, type and degree of hearing loss and to facilitate appropriate treatment and hearing rehabilitation. Vertigo can also occur in the HIV-infected patient usually co-existing with other neurologic symptoms. Vertigo is frequently secondary to CNS involvement but can alsobe due to a direct affectation of the vestibular system by the virus or as a complication of middle ear infection. Thorough clinical and laboratory audio-vestibular assessment is, therefore, necessary to determine the nature and map out a management strategy. The Oral cavity The oral cavity is a prime spot in the head and neck where multiple pathologies can and do frequently occur. The spectrum of oral diseases includes infectious, benign inflammatory, neoplastic, and degenerative processes. Oral candidiasis, Recurrent aphthous ulcers, Herpessimplex, Herpes Zoster (Shingles), Xerostomia, Gingivitis, stomatitis , Condylomata, Hairy leukoplakia, Kaposi’s sarcoma and Non-Hodgkin’s lymphoma are some of the more common lesions Oral candidiasis (thrush) is the most common oral condition in HIV-infected individuals. It is also one of the commonest the commonest ENT manifestations of HIV (1,5). It can present as tender, white, pseudomembranous or plaque-like lesions with underlying erosive erythematous mucosal surfaces (the commonest presentation), the atrophic form, the chronic hypertrophic form or the clinically obvious angular cheilitis, (a non-healing fissure at the oral commissure (1,5). Treatment is with topical antifungals in early disease but systemic in advanced disease with systemic therapy Herpes simplex and varicellazoster also present in the oral cavity. Oral herpes simplex presents as “cold sores” or “fever blisters” but sometimes with bigger lesions on the palate, gingiva or another intraoral mucosal surface. Mild oral herpes infections can usually be treated conservatively, but high-dose oral acyclovir should be used for more severe lesions (1,25). Oral Varicella Zoster presents along the distribution of the trigeminal nerve as crops of vesicles on the hard or soft palate, lips and gingiva or as the corneal infection (zoster ophthalmicus). Verrucae (warts) and condylomata from Human Papilloma Virus infection are other viral lesions that can be found in the oral cavity. Other benign oral cavity lesions include bacterial infections (stomatitis, gingivitis and periodontitis) oral hairy leukoplakia (a whitish, vertically corrugated lesion on anterolateral edge of tongue related to Epstein Barr Virus) and xerostomia (“dryness of mouth” due to salivary gland disease which may be associated with oral “Thrush”). The major malignancies found are Kaposi’s Sarcoma, Non-Hodgkin’s Lymphoma and Squamous Cell Carcinoma. Fifty percent of Kaposi’s Sarcomas are found in the mouth (95% of these on the palate or gingival surface) (1). Oral Non-Hodgkin’s Lymphoma is usually sited on the gingiva and palate with extension to Waldeyer’s ring, especially tonsils. Squamous Cell Carcinoma may also occur in the oral cavity. Careful evaluation is needed to ensure that these lesions are not confused with the many benign lesions that can occur in the oral cavity Salivary glands HIV salivary gland disease (HIV-SGD) is a distinct disorder characterized by recurrent or persistent major salivary gland enlargement and xerostomia (26) The parotids are most frequently affected, often with profound bilateral enlargement. Patients usually present with several months of progressive parotid swelling with minimal tenderness. Xerostomia leads to loss of the antibacterial properties of saliva creates a host of other oral cavity problems such as infection, dental caries, periodontal disease, soreness, fissuring of the buccal mucosa and tongue, and dysphagia. HIV-SGD in the parotid gland is uniquely characterised by the formation of lymphoepithelial cysts within the gland (1, 26)) and the finding of lymphoepithelial cysts in a parotid gland and chronic parotitis especially if bilateral are reasons to offer a patient HIV testing. Pharynx, Larynx and Oesophagus Many of the problems of the oral cavity can also affect the pharynx larynx and oesophagus due to the anatomical and functional relationship. Prominent lesions in the area include candidiasis, herpes simplex, recurrent aphthous ulcerations, acute adult epiglottitis, benign lymphoid hyperplasia, Kaposi’s `sarcoma and Non-Hodgkin’s lymphoma. Candidiasis in the pharynx or oesophagus can lead to odynophagia and or dysphagia, and in the larynx to hoarseness and even aspiration and airway compromise in florid lesions. Appropriate diagnostic studies including endoscopy and radiologic investigations will often help in the diagnosis. Adult acute epiglottitis also deserves special mention since as in the immunocompetent population, it is rapidly progressive and life-threatening. The patient presents with a sore throat and severe odynophagia with drooling, the severity of which does not correlate with a normal oral cavity and oropharyngeal findings on examination. There may be fever, but this is inconstant and the absence may belie the grave danger that the patient is in. If not promptly treated sore throat worsens, and the patient may develop stridor and airway obstruction. In these cases, it is the lack of clinically apparent disease in the setting of such severe symptoms should raise the suspicion of acute epiglottitis. Diagnosis is confirmed by examination of the hypopharynx and larynx, using a flexible nasal endoscope. Management is with intravenous broad-spectrum antibiotics and close airway observation. Preparation should also be made for intubation if necessary. Lack of improvement in 48 to 72 hours is an indication for laryngoscopy and biopsy to rule out infection with an unusual organism or underlying malignancy as airway obstruction is also the most feared complication of malignancy in this area, and these patients are also prone to Kaposi’s Sarcoma and Non-Hodgkin’s lymphoma The neck The major manifestation of HIV in the neck is an enlarging neck mass. This is present in up to 91% of HIV patients who have head and neck manifestations (27). The commonest causes of these masses are HIV lymphadenopathy, infections, parotid gland enlargement and neoplasms. HIV lymphadenopathy can occur in the neck as part of the persistent generalised lymphadenopathy seen in HIV patients. Up to 70% of HIV patients will develop persistent generalised lymphadenopathy within the first few months of infection (28). Infectious processes in the neck can be due to a variety of organisms. Bacterial infections are common, and they may progress to cause deep neck space infections. Majority of the organisms causing these infections are similar to those found in immunocompetent patients, but infections atypical organisms including tuberculous mycobacteria, atypical mycobacteria, fungi (Cryptococcus, Coccidioides, Histoplasma, Pneumocystis) and parasitic (Toxoplasma). Assessment of the neck mass in the HIV patient should be thorough especially to able to identify atypical infections and neoplasms and to chart appropriate treatment. Open neck biopsies are discouraged to prevent seeding of tumours. Similarly, incisions of neck abscesses are to be avoided until chronic granulomatous diseases from atypical infections like tuberculosis are ruled out to avoid creating a wound that would not heal. Conclusion In a nutshell, while there is no AIDS-defining condition specific to the head and neck region, there are many Head and Neck manifestations of HIV. Most patients will initially present to the general practitioner and many to other clinicians. It is important that all clinicians familiarize themselves with the ENT manifestations of HIV so that they are recognised early and appropriate management is promptly instituted.