ENT manifestations in HIV patients

Introduction:


Almost 45 years have passed since the first description of HIV. It still remains a global pandemic. Ofcourse with the current public awareness and treatment methadology available HIV patients are living longer and lead a normal life. The incidence of HIV is also on the wane.


Nearly 80% of HIV infected patients present in the ENT OPD with otolaryngological manifestations. Among the otolaryngological manifestations, oral disease seems to be the most common, occuring in nearly 50% of these patients. The predisposing factors for HIV related ENT conditions include CD4+ cell count of less than 200//μL and Plasma HIV-RNA levels greater than 3000 copies/mL. Some of the other predisposing factors in addition to the above stated ones include: xerostomia, poor oral hygiene, and smoking.


Although ENT manifestations may not be diagnostic of HIV infections, they may be heavily suggestive of such an infection. The presence of certain oral manifestations in patients with known HIV disease who are not on treatment could indicate the progression of the disease. The presence of ENT disease in patients on antiretrovial therapy could be the result of an increase in the plasma HIV-RNA and suggest treatment failure.


Oropharyngeal manifestations of HIV infection:


Oral candidiasis also commonly known as thrush, is the most common oral manifestation of HIV infection. Candidal infections can occur in the oropharynx, hypopharynx and larynx. This condition usually causes severe odynophagia and swallowing difficulties.


The prevalence of candidiasis in HIV positive patients is highly variable ranging between 30-90%.


Oral candidiasis in these patients usually present in three forms:


Pseudomembranous candidiasis:


This is the most common fungal infection in HIV patients. The lesions appear are curd like plaques on the buccal mucosa, tongue, and other oral mucosal surfaces. The plaques can be wiped away leaving behind a red / bleeding underlying surface. These lesions are associated with progression of HIV and can also be used as a clinical marker to define the severity of the infection.


The common organism involved is candida albicans; however involvement of non-albican species such as candida glabrata, and candida dubliniensis have also been described.


Erythematous candidiasis:


These lesions present as red, flat, subtle lesion on the dorsal surface of the tongue, or on the hard/soft palate. This lesion often involves two opposing surfaces, i.e. if a lesion is present on the tongue, the palate should also be examined for a matching lesion. These patients usually complain of a burining sensation, especially while eating spicy / salty food. If hypopharynx, esophagus and larynx are affected, symptoms may progress to severe odynophagia and the patient may have swallowing difficulties. This is rather common in children and they may even require hospitalization. These patients should receive intravenous amphotericin B.


Angular chelitis:


This is a condition that causes red, swollen patches in the corners of the mouth where the lips meet and make an angle. There could be irritation and soreness in the corners of the mouth. The corners of the mouth could be:


Cracked

Crusty

Blistered

Painful

Scaly

Swollen


The warmth and moisture in the corners of the mouth creates a perfect condtion for fungal proliferation.


Treatment involves using topical antifungal cream directly applied to the affected areas atleast 4 times a day for 2 weeks.


Candidiasis can be confirmed in challenging cases from the identification of fungal hyphae in potassium hydroxide preparation (KOH).


Management of mild to moderate cases of erythematous and pseudomembranous candidiasis include clotrimazole torches, nystatin oral suspension. Systemic administration of fluconazole, itraconazole and voriconazole are needed in moderate to severe cases. Voriconazole is reserved for cases of fluconazole resistance. Antifungal therapy should be used for atleast 2 weeks for optimal benefit.


Periodontal and gingival disease:


This is frequently seen in patients with HIV. This condition commonly presents as a red band along the gingival margin. This condition is accompanied by occasional bleeding and discomfort. This condition frequently appear at the anterior teeth, but can also extend to the posterior teeth. It can also present on attached and non attached gigiva as petechia like patches.


Treatment of this condition includes debridement by dentist. Mouth rinses with a 0.12% chlorhexidine gluconate suspension twice daily for two weeks. Maintenance of oral hygiene is rather important in these patients.


Necrotizing ulcerative periodontitis is a marker for severe immune suppression. This condition is characterised by severe pain (deep jaw pain), loosening of the teeth, bleeding, fetid odor, ulcerated gingival papillae and rapid loss of bone and soft tissue. This condition is usually managed by curettage and debridement of all involved tissues, and use of topical antiseptic agents such as 0.12% chlorhexidine gluconate or 10% povidone iodine lavage. Severe cases can be managed by a course of metronidazole. Clindamycin and amoxycillin therapy are also recommended.


Oral Herpes simplex virus infection:


This occurs in nearly 10% of adults with HIV. These lesions present as a small crop of vesicles which produce small, painful ulcerations extending onto adjacent skin and may even coalesce to from giant herpetic lesions. These lesions are often bigger in patients with HIV infection. These lesions could be self limiting and sometimes use of antiviral agents like acyclovir may be needed. These lesions oculd become chronic in HIV children needing intravenous administration of acyclovir.


Hairy Leukoplakia of oral cavity:


These are large asymptomatic lesions involving the tongue. These lesions are caused by Epstein Barr virus. These lesions present as a white corrugated lesion on the lateral borders of the tongue. This lesion cannot be removed by the patient. The terminology of this lesion arises from the appearance of elongated filiform papillae which can be accompanied by white plaque like changes. This condition requires no treatment unless cosmetic concerns arise.


Oral human papilloma virus infections has increased in the era of highly active antiretroviral therapy (HAART therapeutic regimens). This could be due to the fact that the drugs used to treat HIV may be a risk factor for oral HPV infection. The most common HPV subtypes seen in the oral cavity are subtypes 16 and 18. These lesions appear as warts, cauliflower like spiked / raised with a flat surface.


Kaposi sarcoma:


This is the most frequent malignant condition seen in the oral cavity. The prevalence of this condition in the mouth is about 0.4% among HIV patients. Oral cavity is commonly affected and is the first site to be involved by Kaposi sarcoma in nearly 20% of cases. This condition involves the skin and viscera in up to 70% of these patients. In oral cavity the hard palate is most frequently involved, followed by gingival and buccal mucosa as well as the dorsum of the tongue.


Kaposi's sarcoma associated herpes virus was proven to be a co-factor in the presentation of Kaposi's sarcoma in patients with HIV. Kaposi's sarcoma can be macular, nodular, or raised and ulcerated. The color of the lesions can range from red to purple. Early lesions tend to be red, flat and asymptomatic. The color of the lesion darkens as the lesion ages. As these lesions progress, they can become symptomatic due to trauma or infection. Biopsy of the lesion, usually under LA is necessary for the diagnosis. Following the diagnosis of Kaposi's sarcoma oral hygiene is necessary.


Management:


Topical injections of chemotherapeutic agents such as vinblastine sulfate, or even surgical removal or radiation therapy can be considered for treatment. Several surgical techniques have been described including cryotherapy and laser therapy. Systemic chemotherapy is reserved for patients with both oral and extra oral kaposi's sarcoma.


Non-Hodgkin's lymphoma:


This is the second most common malignant condition associated with HIV infection. Lymphomas present as a focal, ulcerated soft tissue mass on the palate or gingival tissues. The affected tissues can be red and inflammed. These lesions can be painful, and progresses rapidly. Suspected lesions can be diagnosed with a biopsy, usually under LA.


Management:


Systemically administered chemotherapy. CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisolone) can be considered the standard approach for patients with aggressive NHL in the context of HIV infection. Surgical debulking may be needed for pain relief and improvement of chewing, swallowing and speech in large exophytic or pedunculated lesions. Radiotherapy may be considered for large lesions that cannot be easily accessed.


Neck manifestations of HIV infection:


Cervical adenopathy is the most common manifestation of HIV infection in the neck. In addition to reactive lymphadenitis, cervical adenopathy may result from tuberculosis, lymphoma, or kaposi's sarcoma in HIV patients. The term HIV lymphadenopathy describes the presence of diffuse lymphadenopathy in two or more sites of the neck for longer than three months. This condition can occur in up to 70% of HIV patients within the first few months after seroconversion, even before any other symptoms of HIV infection appear. This condition is also seen in children. The affected nodes are soft and symmetrical ranging from 1-5 cm in diameter. They are frequently observed in the posterior triangle. Histology is suggestive of reactive follicular hyperplasia. FNAC is indicated in cases of asymmetry, rapidly enlarging lymph nodes, or presence of any other suspicious features. Biopsy under local / general may be necessary in cases of high suspicion of lymphoma.


Salivary gland disease is also not uncommon in HIV infected patients. It usually involves he parotid glands and tends to be bilateral. Sometimes they are cystic and can be accompanied by generalized lymphadenopathy. These patients usually present with a history of progressive parotid swelling with minimal tenderness for over several months. Salivary gland enlargement occurs in approximately 30% of adult patients infected with HIV and in up to 20% of affected children. This condition could represent the first clinical manifestation of HIV. Clinical examination should include assessment of the characteristics of the mass (i.e. fixation) and the function of the facial nerve. The three common causes of parotid enlargement in HIV infected patients are reactive hyperplasia of an intraparotid lymph node, benign lymphoepithelial lesions witih ductal metaplasia and benign lymphoepithelial cysts. FNAC is an effective method of distinguishing benign from malignant parotid lumps. The most common FNAC diagnosis include cystic mass / lymphadenitis and chronic inflammation.


Management:


Treatment of salivary gland enlargement in HIV disease still remains controversial. Superficial parotidectomy has been proposed, but has not been widely accepted. Aspiration of these cystic lesions can offer temporary relief, and injections of tetracycline and doxycycline have been shown to be successful, although with limitations due to the presence of multiple cysts. External irradiation can be considered (24 Gy in 1.5 Gy daily fractions).


Otological manifestations of HIV infection:


Otological manifestation spectrum of HIV infections are rather wide. All three portions of the ear (external, middle and inner ears) can be affected both in adults and pediatric age groups.


External ear:


Seborrheic dermatitis has been reported in 90% of HIV infected patients around periauricular area. Otitis externa caused by pseudomonas aeruginosa and candida albicans can also be seen.

Otalgia is a very frequent symptom in HIV patients and this can be attributed to the disproportionately severe inflammatory changes in the mastoid air cells even in otherwise asymptomatic carriers.

Otitis media with effusion secondary to nasopharyngeal lymphoid hyperplasia / presence of other nasopharyngeal masses is also common in HIV positive patients.

Acute otitis media can also occur, but is usually seen in patients with endstage HIV disease. There is also an increased prevalance of Pneumocystis carinii infected aural polypi in these patients.


Sensorineural hearing loss (unilateral/bilateral) are seen in nearly a third of these patients. These patients manifest down-sloping hearing loss, usually moderate in high frequncies. Speech frequency is not significantly not affected. Histological study of organ of corti in these patients dont reveal any abnormality, except for some cystic changes in the spiral ligament and stria vascularis. Probably there is involvement of retrocochlear pathways / cochlear nerve.


Middle ear infections can be managed using broad-spectrum antibiotics, whereas mastoid exploration may be necessary in cases unresponsive to conservative management.


HIV patients also experience significant dysequilibrium, which is also attributed to the central nervous system pathology. Inner ear abnormalities have also been reported. There is also certain amount of inflammatory endolypmphatic precipitations causing Meniere's like manifestation.


Unilateral / Bilateral facial nerve palsy occurs nearly 100 times more in HIV infected patients. Facial nerve neuropathy can occur at any stage of HIV infection. It may even precede the appearance of HIV antibodies, and are known to occur frequently in HIV carriers than in patients with full blown AIDS. Peripheral facial nerve neuropathy are usually self limiting and could be due to idiopathic or due to herpes virus infection (Ramsay Hunt syndrome). Treatment for this condition include acyclovir 800 mg five times a day for seven days and prednisolone 30 mg once a day for 5 days with tapering of the starting dosee in three day intervals. Facial nerve palsy can be seen in end stage patients as an isolated entity or as a part of multiple cranial nerve involvement.


Nasal manifestations of HIV infection:


Nasal manifestations are not uncommon amoung HIV patients. Rhinosinusitis is known to occur in nearly half of these patients. Despite the fact that cellular immunity is compromised in these patients, studies have revealed excessive production of IgE, which is suggestive of active allergic rhinitis in the absence of parasitic infections. There is a two fold increase in the incidence of allergic symptoms in HIV infected patients. These patients usually present with clear rhinorrhoea and nasal congestion. Budesonide nasal spray is preferred to fluticasone due to its significantly longer half life. Monteleukast has also been successfully used in these patients.


In addition to compromised immunity, there is also evidence of impaired mucociliary clearance in these patients. This accounts for the higher incidence of rhinosinusities in these patients. There is no difference in bacteriology in these patients. Atypical bacteria can be seen in patients with decreased CD4 count. The atypical organims isolated include alternaria alternata, aspergillus, pseudallescheria boydii, cryptococcus, candidia albicans, acanthamoeba castellani, microsporidian and legionella pneumophilia.


These patients can be managed with standard out patient medical therapy with oral antibiotics for 3 weeks and nasal decongestants. In chronic cases the treatment is to be prolonged for 4-6 weeks. Oral antibiotics administered include amoxicillin, amoxycillin with clavulanic acid, or cefuroxime. It the response to antibiotics is partial then CD4 count should be less than 200. In chronic cases the coverage should be broadened to include pseudomonas, staphylococci, and anaerobic species. These patients can be managed using a combination of fluoroquinolones and clindamycin or metronidazole.

Image showing pseudomembranous candidiasis

Image showing chelitis