More or Ear, Nose and Throat manifestation, many

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 includes skin 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 various infections, 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 of disease 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 of these 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 confused with 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 upper aero-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
immunocompetent patients, 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 also be 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, Herpes simplex, 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 varicella zoster
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.