Sinusitis in HIV-l JOHN J. ZURLO, M.D., Bethesda, Bethesda,
Mary/and,
Bethesda,
Maryland
and Washington,
Infection !RWINM. FEUERSTEIN,M.D., D.c., ROBERTLEBOVICS,M.D., H. CLIFFORDLANE,M.D.,
Mary/and,
PURPOSE To determine the clinical and radiographic charact8rifstics of sinu&is in patilults with human immunodeficiency virus type 1 (HIV-l) infection. PATIENTS AND METHOD& A retrospective study was performed that identified all HIV-l-infeoted patients with sinus radiograph sinus computed tom* or magnetic resonance imaging of the head between 1982 and 1989 (n = 145). Medical record review detailed the clinical course and laboratory parameters in all patients. RESULT Eighty-nine patients had radiographic evidence of ainusitig 75 patients had adequate cIinicaI data and comprise the study group. Acute sinusitis was seen in 10 patients (13%), while alI 75 patient8 had muccmal thickening indicative of chronic sinusitis. Fifty patienta (67%) were symptomatic with fever, nasal congestion or discharge, and headache being the most common symptoms; nineteen patients (25%) were asymptomatic when their radiographs showed active disease. The mean CD4 count for the group was 376 celWmm3; 32 (43%) had CD4 wunts leas than or equal to 106 c811s/mm3. Twenty-three patients (31%) received antibiotice orally, parenterally, or both. CONCLUSIONEk Sinusitis appears to occur frequently in HIV-infected patien@ is often asymptomatic, may be recurrent or refractory, and may be associated with declining immunocompetalc8 in HIV-infected patients.
A
variety of infectious conditions affecting the head and neck have been described in patients with human immunodeficiency virus type 1 (HIV1) infection. Oropharyngeal candid&is [l], recurrent herpes simplex stomatitis [2], and oral hairy leukoplakia [3] are the most commonly encountered infections. Infections of the paranasal sinuses have been reported in HIV-infected patients, in both adults and children, although most have been in the form of single case reports dating back to 1984 [4-71. In such patients, sinus infection has been described to be both severe and recurrent. In children, a high concordance between sinusitis and otitis media has been reported [7]. In a retrospective review, Lamprecht and Wiedbrauck [8] described a variety of ear, nose, and throat complications in their group of 181 HIV-infected patients with different stages of disease. Twenty-eight patients had radiographic evidence of sinus disease and all had symptomatic HIV-l infection. Fineman and co-worker8 [9] reported on the use of radionuclide scintigraphy to localize infections in febrile patients with acquired immunodeficiency syndrome (AIDS). Although the majority of patients had pulmonary or colonic lesions, seven patients were found to have sinusitis, in all cases judged to be clinically significant. Overall, little is known about the incidence of sinusitis in this population, its clinical characteristics, radiographic appearance, or response to therapy. Having observed a high frequency of sinusitis among our own HIV-infected patients, we undertook a retrospective review of sinusitis in these patients.
PATIENTS AND METHODS
From the National Institute of Allergy and Infectious Diseases (JJZ. HCL) and the Warren Grant Magnuson Clinical Center (IMF. RL), National Institutes of Health, Bethesda, Maryland, and Georgetown University Hospital (IMF), Washington, D.C. Requests for reprints should be addressed to John J. Zurlo. M.D., P.O. Box 850. Hershey Medical Center, Hershey, Pennsylvania 17033. Manuscript submitted July 10. 1991, and accepted in revised form March 19, 1992.
All patients diagnosed with HIV-l infection who were seen at the National Institutes of Health (NIH) Clinical Center between 1982 and 1989 were compiled from a database containing immunologic data, including CD4 count, on each patient. These patients were cross-referenced with the Medical Information System, a computer database at the Clinical Center that has stored hospital records on all patients seen at the NIH, to determine which patients had previously had one or more of the following imaging studies: paranasal sinus radiographs, August
1992
The American
Journal
of Medicine
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93
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SINUSITIS IN HIV-l INFECTION / ZURLO ET AL
sinus computed tomography (CT), or magneticres- thickness that almost invariably accompaniedthe onanceimaging (MRI) of the head.Of 752patients cyst.& with HIV-l infection, a total of 145 patients were found to have had one or more imaging studies. Clinical Data Retrieval Medical records were reviewed for each patient Radiographic Data Retrieval with abnormalradiographs.The following informaRadiographswerereviewedindependently of the tion was retrieved: sex, race, age at time of first medical record review. The radiograph reviewer radiographic evidence of sinusitis, HIV-l risk was unaware of the clinical status of any patient group, previous history of intranasal cocaine use, during his review. MRI was performed on a Picker and previoushistory of sinusdisease.Also extracted Vista 0.5 tesla whole body imager (Picker Interna- werepreviousdiagnosisof AIDS, AIDS-defining illtional, Highland Heights, OH). Imaging sequences ness,and CD4 count at the time nearestthe first were: Tl-weighted spin echo, axial and coronal, radiographicevidenceof sinusitis. Pertinent sinuswithout and with gadolinium, TR 300-4OO/TE12- related symptoms at the time of the first abnormal 20, lo-mm thick sections;TB-weighted spin echo, radiograph were recorded,including sinus tenderaxial, TR 2OOOPTE 100,7-mm thick sections.Sinus ness, sinus pain, and nasal congestion and disCT wasperformedon a GeneralElectric 9600third- charge;fever and headachewere consideredpertigenerationscanner(GeneralElectric Medical Sys- nent if sinusitis could not be ruled out as the cause. tems, Milwaukee, WI). Scans were taken in both Outcome of the initial sinusitis episodewas determined both clinically and radiographically. A axial and coronal planes,without intravenouscontrast material, using 5-mm thick sections. clinical outcome was determined to be one of the Acute sinusitis was defined as the presenceof an following: “resolved,” if the symptom(s) was/were air fluid level within a sinus cavity. Chronic sinus- specifically addressedand found to be no longer itis was defined as the presenceof mucoperiosteal present in subsequentprogressnote entries; “perthickening. sistent,” if the symptom(s) was/were specifically There were two sinusitis grading scalesfor each addressedandremainedpresentin subsequentpropatient, one for the patient as a whole and one for gressnote entries, irrespectiveof specific therapy; each individual sinus. The scorefor the first scale “uncertain,” if the symptom(s) was/werenot adwas based on degreeof abnormality of the most dressedin subsequentnotesor could otherwisenot severelyaffected sinus. For this scale,eachpatient be determined; “not applicable,” if the patient was receiveda scoreof 1 to 4, with 1 being normal and 4 asymptomatic at the time of the initially abnormal being either acute sinusitis or severechronic dis- radiograph. Radiographic outcome was based on ease.For the grading of chronic sinusitis on this subsequent radiographs and judged to be unscale(most typically maxillary sinus), a radial line changed,worse, resolved/improved, or recurrent wasconstructedfrom the wall of the maxillary sinus disease. to the center of the sinus and divided into thirds. Thickening confined to the most peripheral third RESULTS wasgradedas2 (mild), that extendingto the middle Of the 145patients identified, radiographswere was gradedas 3 (moderate),and that extending to unavailable for six. Radiographswere reviewedfor the internal third or filling the sinus was graded4 the remaining 139 patients; 89 patients had evi(severe).A similar approachwas used for the re- denceof sinusitis, of which group 14 medical remaining sinuses.This scale was absolute from pa- cords were either unavailable or contained incomtient to patient, and wasnot a sliding relative scale. plete information. The remaining 75 patients A secondscale,alsofrom 1 to 4, wasestablishedto comprise the study group. Table I lists demographiccharacteristicsof the determine both the relative and absolute involvement of eachindividual sinus. A normal sinus was patient group. The majority were male (96%)and graded as 1; acute or severechronic sinusitis was most were either homosexualor bisexual.The magradedas 4; intermediate levelsof 2 or 3 were used jority of patients (79%)had a diagnosisof AIDS at asnecessaryto conveywhich sinuswasmore severe- the time of their first abnormalradiograph.Most of these patients had Kaposi’s sarcoma. ly affected as applicable. MucosaI retention cysts were scored independently. Although the cysts often extendedinto the Radiographic Results A total of 10 patients had radiographicevidence center of the sinus,they did not influence the score for mucosal thickening, which was determined of acute sinusitis, while all 75 patients had some based on the surrounding, more diffuse mucosal degreeof chronic sinusitis. Chronic sinusitis was
158
August 1992 The American Journal of Medicine
Volume 93
SINUSITIS IN HIV-1 INFECTION / ZURLO ET AL TABLE I DemographicData of 75 HIV-Mected Patients With Sinusitis Characteristic Total no. with sinusitis Mean age Male/female
Maxillary No.(%I
Ethmoid
El 72/3
Sphenoid
Risk group Homosexual or bisexual HomosexuaMVDA $hnfusion-acquired Prior history of sinusitis Yi?S No Uncertain
Frontal 10
0
20
30
40
60
50
Number of Patients 8fll)
Flgure
“i El
tally
1. Number documented
of HIV-infected involvement for
patients with radiographieach of the paranasal si-
HMstv of cocaine abuse No Uncertain Total no. with AIDS Previous opportunistic infections or AIDS-related malignancies Kaposi’s sarcoma Pfleumocystis carinii pneumonia CMV retinitis Disseminated Mycobacterium avium complex Cryptococcosis
TABLE II
59 (79)
Clinical Characteristicsof 75 Patients With Sinusitis ii I:;;* 1; y$: NoP;iratients
Characteristic
No.(%I
with symptoms
50 (67)
4 (7)* J
DA = intravenousdrugabuser; CMV = cytomegalovirus. lumbers in parentheses are percentagesoi 59 patients with AIDS.
mild in 42 patients, moderate in 16, and severein 17. Mucosal retention cysts were seen in 20 patients. Figure 1 shows the individual sinusesinvolved. The maxillary sinuswas involved in 75%of the patient group, followed by ethmoid involvement (55%).Simultaneous maxillary and ethmoid involvement was seenin 27 patients (36%);either the maxillary or ethmoid sinuseswere involved in 70 patients (93%). Clinical Results
Table II showsthe clinical characteristicsof the patient group. Two thirds of the patients were symptomatic. The most common symptoms were fever, nasalcongestionor discharge,and headache. All patients with either acute sinusitis (10 of 10)or severechronic sinusitis (17 of 17)weresymptomatic, while 12 of 16 (75%)and 21 of 42 (50%)with moderate and mild chronic sinusitis, respectively, were symptomatic. Nineteen patients (33%)had no sinus symptoms despite radiographic evidenceof sinus disease.For ail of these patients, the only radiographic study performed was a head MFU scanfor non-sinus-related indications in all cases.Six demonstratedmild ethmoid disease alone, four demonstrated mild maxillary diseasealone, and the remaining nine
s: I% 15 (20)
Nasal congestion Nasal discharge Headache Sinus pain Postnasal drip Sinus tenderness Tooth pain Seizures
“: IiT’ F# :I:; 19 (25)
No symptoms Uncertain symptoms
6 (8)
Antibiotics given Intravenous Oral Both > 14 days > 1 course Decongestants/antihistamines
4 (5) 16 (21) 351;; 4 (5) given
19 (25)
Nasal steroids given
4 (5)
No. of patients requiring drainage or surgery
4 (5)
demonstrated abnormalities in multiple sinuses. For the six remaining patients (8%)with sinus disease,either a sinus seriesor sinus CT scanwas obtained, presumably for sinus-related symptoms, but specific referable symptoms were not documented. Three had mild maxillary diseaseand the remaining three demonstrated abnormalities in multiple sinuses. Four patients required simple drainageor surgical proceduresfor persistentsinus infection. Three of the four had CD4 counts below 100/mm3. All receivedmore than 14 days of antibiotics; three of
August 1992 The American Journal of Medlclne
Volume 93
159
SlNUSlTfS IN HIV-l INFECllON / ZURLO ET AL 40 3 35
$ .m %
3o 25
a “0
20
iii
15
g
10
z
5
!i = 276 cells/mm3
l-l o-loo
101-200
201-300
301-400
401.so0
>soo
CD4 count Figure tients
2. CD4 with
count radiographically
distribution among 75 HIV-infected documented sinusitis. j; = mean.
pa-
the four had both clinical and radiographic resolution. Sinus cultures were obtained from a total of four patients. cy-Hemolytic Streptococcus was found in three of the four, although never as the sole pathogen. Coagulase-negative Staphylococcus was cultured from two patients, one of whom also had Veillonella parvula cultured. Multiple organisms were cultured from one patient, including Mycobacteriurn avium complex (MAC), Haemophilus influenzae, Corynebacterium species, Citrobacter diversus, Proteus mirabilis, and Propionibacterium acnes. This patient also had disseminated MAC. Figure 2 shows the CD4 counts for the entire group of patients with sinusitis. Thirty-two (43%) had CD4 counts less than or equal to 196 celWmm3, while 16 had CD4 counts greater than 500/mm3. Outcome In terms of the clinical outcome of symptomatic patients, symptoms resolved in 23 patients (46%), persisted in five patients (lo%), and were of uncertain outcome in 22 patients (44%). Radiographic abnormalities improved or resolved in 13 patients (17%), were unchanged in 13 patients (17%), became worse in nine patients (12%), and recurred in one patient (1%). No follow-up radiographs were obtained in 39 patients (52%). The mean time of follow-up for the entire group from the time of the first radiographic evidence of sinusitis was 8.5 months (range: 0 to 38 months). Among the 13 patients with radiographic improvement, clinical resolution of symptoms was noted in 11. Antibiotics did not appear to affect the clinical outcome but may have had a role in hastening radiologic improvement. Fifteen of 18 patients (83%) with adequate follow-up who received antibiotics had resolution of symptoms as did nine of 11 pa160
August 1992 The American Journal of Medlclne
tients (82%) who did not receive antibiotics. Radiographically, nine of the 12 patients (75%) with follow-up radiographs who received antibiotics had radiographic improvement, while only four of 11 patients (36%) who did not receive antibiotics improved radiographically. Eight of the nine patients with radiographic improvement also improved clinically. For the 19 patients who were asymptomatic despite radiographic evidence of sinus disease, the mean follow-up was 8.7 months (range: 1 to 27 months). There were follow-up radiographs for four. Three of the follow-up films were unchanged, while one showed improvement. Eighteen of the 19 patients remained asymptomatic. One patient developed frontal headaches; his follow-up radiograph remained unchanged. For the six patients with radiographic evidence of sinus disease seen in radiographs ordered specifically to evaluate the sinuses (sinus series, sinus CT) but whose medical records did not document sinusrelated symptoms, two had follow-up radiographs. One showed minimal progression of radiographic abnormalities and the other revealed marked worsening that correlated with the development of fever and headaches. The remaining five patients remained asymptomatic. COMMENTS In the present study, we have retrospectively evaluated sinusitis in patients with HIV-l infection and found it to be common. However, as with any retrospective study, there are a few caveats that must be considered. First, we chose to define sinusitis radiographically as an objective means of identifying our study population, since there appeared to be no satisfactory objective clinical criteria by which patients could be retrospectively selected for inclusion. For some patients, particularly those for whom no sinus-related symptoms were described in the medical record and for whom radiographs revealed only mild chronic disease, the clinical significance of the radiographic findings may be suspect. This is especially true for patients whose only imaging study was an MRI scan of the head (n = 21; two with symptoms, 19 without). For six of these patients, only mild ethmoid disease was observed and all were asymptomatic. An age-matched control group of non-HIV-infected patients who had MRI scans of the head was not available. Since the mean follow-up period for these patients was relatively short and since they were not specifically followed for sinus-related symptoms, it is conceivable that a substantial proportion would have developed sinus disease at a later time, particularly those with abnormalities involving multiple sinuses. It is also
Volume 93
SINUSITIS IN HIV-l INFECTION / ZURLO ET AL
possible that for sinus evaluation, MRI lacks adequate specificity in an asymptomatic population. Second,although a list of pertinent clinical symptoms of sinus diseasewaschosenprior to reviewing the medical records,it was not alwayscertain that the symptoms recordedin the medical record were in fact secondary to underlying sinusitis. Headaches,for instance,may have had other causes.If symptoms were believed by the examining physician to be related to a nonsinus cause,they were discounted. However, if symptoms could not be ruled out as being sinus-related,they were included. This may have resulted in overinclusivenessin our symptom list. Also, the clinical outcome was sometimesdifficult to determine. Very often, even for patients who were treated with antimicrobial agentsfor presumedsinus infection, little or no specific comment was made as to the clinical outcome in subsequentnotes.Since we did not construethe lack of documentation asa goodclinical response,a large percentageof our patient group werejudged by us to have an uncertain clinical outcome. Similarly, it could not always be ascertained whether patients were treated for their sinus disease.Since our patient population is entirely referral-based,it is likely that patients who may have developedsymptomatic sinusitis outside the NIH would have been treated by their referring physicians. Therefore, our data are likely to underestimate the true incidence of symptomatic sinus diseasein our population as well asthe true frequency of treatment with both decongestants and antibiotics. Given those limitations, much can be gleaned from our data. Sinusitis appearsto occur with significant frequencyin patients with HIV-l infection. Like sinusitis in non-HIV-infected patients, the maxillary sinuses were moat commonly involved [lo]. The paranasal sinusesmay be an important site of occult fever in this patient group given the fact that fever was the only symptom in five of the 24 patients with fever. Our data suggestthat the incidence of sinus disease increasesas the CD4 count declines,as is true of many infections in the setting of HIV-l disease[ll]. Sinceour patient population is highly selected,and since no systematic prospectivemeansto identify sinusitis in the group was used, it is difficult to derive meaningful incidenceestimates from our data. Other than low CD4 count, we did not identify any other obvious risk factors for sinusitis. A prior history of sinusitis was elicited from only eight patients. Interpretation of such a history is difficult consideringthat many patients claim to have a history of sinus diseaseor sinus symptoms without radiographicor clinical documentation.A history of
intranasal cocaineabusewas similarly difficult to interpret retrospectivelysincefrequencyand duration of cocaineusewere generallynot documented and since such a history was uncertain for 21 patients. It is intriguing to speculate as to the etiologic mechanism(s)underlying sinusitis in HIV-infected patients. A defect in humoral immunity may be important. HIV-infected patients are known to havehumoral immune dysfunction with polyclonal hypergammaglobulinemiaand defective antibody production in responseto specificantigens [12-141. It has also been well describedthat other patients with humoral immunodeficiency disordershaverecurrent sinus and pulmonary infections, typically secondaryto encapsulatedbacterialpathogenssuch as H. influenzae and Streptococcus pneumoniae [15,16].These pathogenshave also been described anecdotally to causesinusitis in HIV-infected patients. The same organismshave been reported to account for up to 10%of bacterial pneumoniasin this population [17]. One must also consider the possibility that nonbacterialpathogens,particularly respiratoryviruses,herpesviruses,or evenHIV-l itself, may be important etiologic agents.Finally, impaired sinus drainagesecondaryto lymphoid hyperplasiaor nonspecificmucosalinflammation may be contributory factors. In summary, our data indicate that sinusitis is a frequent problem occurring in patients with HIV-l infection, likely related to declining immunocompetence.Prospectivestudies should be undertaken to determine: (1) the true incidenceof sinusitis in HIV-infected patients; (2) the preciseassociationof sinusitis with declining immunocompetence;(3) the microbiologic etiology of infection; (4) the proper duration of antimicrobial therapy; and (5) the role of surgical intervention. ACKNOWLEDGMENT We thank Dr. Michael Polis for his valuable suggestions statistical considerations for this manuscript.
as regards editorial and
REFERENCES 1. Klein RS, Harris CA, Small CB, Mall B, Lesser M. Friedland GH. Oral candidiasis
in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N Engl J Med 1984; 311: 354-8. 2. Centers for Disease Control. Oral viral lesion (hairy leukoplakia) associated with acquired immunodeficiency syndrome. MMWR 1985; 34: 54940. 3. Quinnan GV Jr, Masur H, Rook AH, et a/. Herpesvirus infections in the acquired immune deficiency syndrome. JAMA 1984; 252: 72-7. 4. Marcusen DC, Sooy CD. Otolaryngologic and head and neck manifestations of acquired immunodeficiency syndrome (AIDS). Laryngoscope 1985; 95: 401-5. 5. Poole MD, Postma D, Cohen MS. Pyogenic otorhinologic infections in acquired immune deficiency syndrome. Arch Otolaryngol 1984; 110: 130-l. 6. Lim DT, Enright T, Shetty R, Park L. Asthma, recurrent sinopulmonary disease and HIV infection. Ann Allergy 1988; 61: 175-6. 7. Durrani FK, Church JA. Chronic otitis media/sinusitis as presenting infection
August 1992 The American Journal of Medicine
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SINUSITIS IN HIV-l INFECTION / ZURLO ET AL in pediatric AIDS [abstract]. Ann Allergy 1986; 56: 516. 8. Lamprecht J, Wiedbrauck C. Sinusitis and other typical ENT diseases within the scope of acquired immunologic deficiency syndrome (AIDS). HNO (Berlin) 1988; 36: 489-92. 9. Fineman DS. Palestro CJ. Kim CK, eta/. Detection of abnormalities in febrile AIDS patients with In-l 1 l-labeled leukocyte and Ga-67 scintigraphy. Radiology 1989; 170: 677-80. 10. Gwaltney JM Jr. Sinusitis. In: Mandell GL, Douglas RG. Bennett JE, editors. Principles and practice of infectious diseases. New York: Churchill Livingstone. 1990: 510-4. 11. Masur H. Ognibane FP. Yarchoan R. et a/. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med 1989: 111: 223-31. 12. Lane HC, Masur H. Edgar LC. et al. Abnormaliiies of B-cell activation and
162
August 1992 The American Journal of Medicine
immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983; 3091 453-8. 13. Chess Q, Daniels J. North E, et a/. Serum immunoglobulin elevations in the acquired immunodeficiency syndrome (AIDS): IgG, IgA, IgM. and IgD. Diagn lmmunol 1984; 2: 148-53. 14. Pahwa SG, Quilop MTJ. Lange M, et a/. Defective B-lymphocyte function in homosexual men in relation to the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101: 757-63. 15. Hermans PE, Diaz-Buxo JA. Stobo JD. Idiopathic late onset immunoglobulin deficiency. Clinical observations in 50 patients. Am J Med 1976; 61: 221-32. 18. Lederman HM. Winkelstein JA. X-linked agammagfobulinemia: an analysis of 96 patients. Medicine (Baftimore) 1985; 641 145-56. 17. Polsky B. Gold JW. Whimbey E, et a/. Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986; 104: 38-43.
Volume 93
Mary/and,
Bethesda,
Maryland
and Washington,
Infection !RWINM. FEUERSTEIN,M.D., D.c., ROBERTLEBOVICS,M.D., H. CLIFFORDLANE,M.D.,
Mary/and,
PURPOSE To determine the clinical and radiographic charact8rifstics of sinu&is in patilults with human immunodeficiency virus type 1 (HIV-l) infection. PATIENTS AND METHOD& A retrospective study was performed that identified all HIV-l-infeoted patients with sinus radiograph sinus computed tom* or magnetic resonance imaging of the head between 1982 and 1989 (n = 145). Medical record review detailed the clinical course and laboratory parameters in all patients. RESULT Eighty-nine patients had radiographic evidence of ainusitig 75 patients had adequate cIinicaI data and comprise the study group. Acute sinusitis was seen in 10 patients (13%), while alI 75 patient8 had muccmal thickening indicative of chronic sinusitis. Fifty patienta (67%) were symptomatic with fever, nasal congestion or discharge, and headache being the most common symptoms; nineteen patients (25%) were asymptomatic when their radiographs showed active disease. The mean CD4 count for the group was 376 celWmm3; 32 (43%) had CD4 wunts leas than or equal to 106 c811s/mm3. Twenty-three patients (31%) received antibiotice orally, parenterally, or both. CONCLUSIONEk Sinusitis appears to occur frequently in HIV-infected patien@ is often asymptomatic, may be recurrent or refractory, and may be associated with declining immunocompetalc8 in HIV-infected patients.
A
variety of infectious conditions affecting the head and neck have been described in patients with human immunodeficiency virus type 1 (HIV1) infection. Oropharyngeal candid&is [l], recurrent herpes simplex stomatitis [2], and oral hairy leukoplakia [3] are the most commonly encountered infections. Infections of the paranasal sinuses have been reported in HIV-infected patients, in both adults and children, although most have been in the form of single case reports dating back to 1984 [4-71. In such patients, sinus infection has been described to be both severe and recurrent. In children, a high concordance between sinusitis and otitis media has been reported [7]. In a retrospective review, Lamprecht and Wiedbrauck [8] described a variety of ear, nose, and throat complications in their group of 181 HIV-infected patients with different stages of disease. Twenty-eight patients had radiographic evidence of sinus disease and all had symptomatic HIV-l infection. Fineman and co-worker8 [9] reported on the use of radionuclide scintigraphy to localize infections in febrile patients with acquired immunodeficiency syndrome (AIDS). Although the majority of patients had pulmonary or colonic lesions, seven patients were found to have sinusitis, in all cases judged to be clinically significant. Overall, little is known about the incidence of sinusitis in this population, its clinical characteristics, radiographic appearance, or response to therapy. Having observed a high frequency of sinusitis among our own HIV-infected patients, we undertook a retrospective review of sinusitis in these patients.
PATIENTS AND METHODS
From the National Institute of Allergy and Infectious Diseases (JJZ. HCL) and the Warren Grant Magnuson Clinical Center (IMF. RL), National Institutes of Health, Bethesda, Maryland, and Georgetown University Hospital (IMF), Washington, D.C. Requests for reprints should be addressed to John J. Zurlo. M.D., P.O. Box 850. Hershey Medical Center, Hershey, Pennsylvania 17033. Manuscript submitted July 10. 1991, and accepted in revised form March 19, 1992.
All patients diagnosed with HIV-l infection who were seen at the National Institutes of Health (NIH) Clinical Center between 1982 and 1989 were compiled from a database containing immunologic data, including CD4 count, on each patient. These patients were cross-referenced with the Medical Information System, a computer database at the Clinical Center that has stored hospital records on all patients seen at the NIH, to determine which patients had previously had one or more of the following imaging studies: paranasal sinus radiographs, August
1992
The American
Journal
of Medicine
Volume
93
157
SINUSITIS IN HIV-l INFECTION / ZURLO ET AL
sinus computed tomography (CT), or magneticres- thickness that almost invariably accompaniedthe onanceimaging (MRI) of the head.Of 752patients cyst.& with HIV-l infection, a total of 145 patients were found to have had one or more imaging studies. Clinical Data Retrieval Medical records were reviewed for each patient Radiographic Data Retrieval with abnormalradiographs.The following informaRadiographswerereviewedindependently of the tion was retrieved: sex, race, age at time of first medical record review. The radiograph reviewer radiographic evidence of sinusitis, HIV-l risk was unaware of the clinical status of any patient group, previous history of intranasal cocaine use, during his review. MRI was performed on a Picker and previoushistory of sinusdisease.Also extracted Vista 0.5 tesla whole body imager (Picker Interna- werepreviousdiagnosisof AIDS, AIDS-defining illtional, Highland Heights, OH). Imaging sequences ness,and CD4 count at the time nearestthe first were: Tl-weighted spin echo, axial and coronal, radiographicevidenceof sinusitis. Pertinent sinuswithout and with gadolinium, TR 300-4OO/TE12- related symptoms at the time of the first abnormal 20, lo-mm thick sections;TB-weighted spin echo, radiograph were recorded,including sinus tenderaxial, TR 2OOOPTE 100,7-mm thick sections.Sinus ness, sinus pain, and nasal congestion and disCT wasperformedon a GeneralElectric 9600third- charge;fever and headachewere consideredpertigenerationscanner(GeneralElectric Medical Sys- nent if sinusitis could not be ruled out as the cause. tems, Milwaukee, WI). Scans were taken in both Outcome of the initial sinusitis episodewas determined both clinically and radiographically. A axial and coronal planes,without intravenouscontrast material, using 5-mm thick sections. clinical outcome was determined to be one of the Acute sinusitis was defined as the presenceof an following: “resolved,” if the symptom(s) was/were air fluid level within a sinus cavity. Chronic sinus- specifically addressedand found to be no longer itis was defined as the presenceof mucoperiosteal present in subsequentprogressnote entries; “perthickening. sistent,” if the symptom(s) was/were specifically There were two sinusitis grading scalesfor each addressedandremainedpresentin subsequentpropatient, one for the patient as a whole and one for gressnote entries, irrespectiveof specific therapy; each individual sinus. The scorefor the first scale “uncertain,” if the symptom(s) was/werenot adwas based on degreeof abnormality of the most dressedin subsequentnotesor could otherwisenot severelyaffected sinus. For this scale,eachpatient be determined; “not applicable,” if the patient was receiveda scoreof 1 to 4, with 1 being normal and 4 asymptomatic at the time of the initially abnormal being either acute sinusitis or severechronic dis- radiograph. Radiographic outcome was based on ease.For the grading of chronic sinusitis on this subsequent radiographs and judged to be unscale(most typically maxillary sinus), a radial line changed,worse, resolved/improved, or recurrent wasconstructedfrom the wall of the maxillary sinus disease. to the center of the sinus and divided into thirds. Thickening confined to the most peripheral third RESULTS wasgradedas2 (mild), that extendingto the middle Of the 145patients identified, radiographswere was gradedas 3 (moderate),and that extending to unavailable for six. Radiographswere reviewedfor the internal third or filling the sinus was graded4 the remaining 139 patients; 89 patients had evi(severe).A similar approachwas used for the re- denceof sinusitis, of which group 14 medical remaining sinuses.This scale was absolute from pa- cords were either unavailable or contained incomtient to patient, and wasnot a sliding relative scale. plete information. The remaining 75 patients A secondscale,alsofrom 1 to 4, wasestablishedto comprise the study group. Table I lists demographiccharacteristicsof the determine both the relative and absolute involvement of eachindividual sinus. A normal sinus was patient group. The majority were male (96%)and graded as 1; acute or severechronic sinusitis was most were either homosexualor bisexual.The magradedas 4; intermediate levelsof 2 or 3 were used jority of patients (79%)had a diagnosisof AIDS at asnecessaryto conveywhich sinuswasmore severe- the time of their first abnormalradiograph.Most of these patients had Kaposi’s sarcoma. ly affected as applicable. MucosaI retention cysts were scored independently. Although the cysts often extendedinto the Radiographic Results A total of 10 patients had radiographicevidence center of the sinus,they did not influence the score for mucosal thickening, which was determined of acute sinusitis, while all 75 patients had some based on the surrounding, more diffuse mucosal degreeof chronic sinusitis. Chronic sinusitis was
158
August 1992 The American Journal of Medicine
Volume 93
SINUSITIS IN HIV-1 INFECTION / ZURLO ET AL TABLE I DemographicData of 75 HIV-Mected Patients With Sinusitis Characteristic Total no. with sinusitis Mean age Male/female
Maxillary No.(%I
Ethmoid
El 72/3
Sphenoid
Risk group Homosexual or bisexual HomosexuaMVDA $hnfusion-acquired Prior history of sinusitis Yi?S No Uncertain
Frontal 10
0
20
30
40
60
50
Number of Patients 8fll)
Flgure
“i El
tally
1. Number documented
of HIV-infected involvement for
patients with radiographieach of the paranasal si-
HMstv of cocaine abuse No Uncertain Total no. with AIDS Previous opportunistic infections or AIDS-related malignancies Kaposi’s sarcoma Pfleumocystis carinii pneumonia CMV retinitis Disseminated Mycobacterium avium complex Cryptococcosis
TABLE II
59 (79)
Clinical Characteristicsof 75 Patients With Sinusitis ii I:;;* 1; y$: NoP;iratients
Characteristic
No.(%I
with symptoms
50 (67)
4 (7)* J
DA = intravenousdrugabuser; CMV = cytomegalovirus. lumbers in parentheses are percentagesoi 59 patients with AIDS.
mild in 42 patients, moderate in 16, and severein 17. Mucosal retention cysts were seen in 20 patients. Figure 1 shows the individual sinusesinvolved. The maxillary sinuswas involved in 75%of the patient group, followed by ethmoid involvement (55%).Simultaneous maxillary and ethmoid involvement was seenin 27 patients (36%);either the maxillary or ethmoid sinuseswere involved in 70 patients (93%). Clinical Results
Table II showsthe clinical characteristicsof the patient group. Two thirds of the patients were symptomatic. The most common symptoms were fever, nasalcongestionor discharge,and headache. All patients with either acute sinusitis (10 of 10)or severechronic sinusitis (17 of 17)weresymptomatic, while 12 of 16 (75%)and 21 of 42 (50%)with moderate and mild chronic sinusitis, respectively, were symptomatic. Nineteen patients (33%)had no sinus symptoms despite radiographic evidenceof sinus disease.For ail of these patients, the only radiographic study performed was a head MFU scanfor non-sinus-related indications in all cases.Six demonstratedmild ethmoid disease alone, four demonstrated mild maxillary diseasealone, and the remaining nine
s: I% 15 (20)
Nasal congestion Nasal discharge Headache Sinus pain Postnasal drip Sinus tenderness Tooth pain Seizures
“: IiT’ F# :I:; 19 (25)
No symptoms Uncertain symptoms
6 (8)
Antibiotics given Intravenous Oral Both > 14 days > 1 course Decongestants/antihistamines
4 (5) 16 (21) 351;; 4 (5) given
19 (25)
Nasal steroids given
4 (5)
No. of patients requiring drainage or surgery
4 (5)
demonstrated abnormalities in multiple sinuses. For the six remaining patients (8%)with sinus disease,either a sinus seriesor sinus CT scanwas obtained, presumably for sinus-related symptoms, but specific referable symptoms were not documented. Three had mild maxillary diseaseand the remaining three demonstrated abnormalities in multiple sinuses. Four patients required simple drainageor surgical proceduresfor persistentsinus infection. Three of the four had CD4 counts below 100/mm3. All receivedmore than 14 days of antibiotics; three of
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SlNUSlTfS IN HIV-l INFECllON / ZURLO ET AL 40 3 35
$ .m %
3o 25
a “0
20
iii
15
g
10
z
5
!i = 276 cells/mm3
l-l o-loo
101-200
201-300
301-400
401.so0
>soo
CD4 count Figure tients
2. CD4 with
count radiographically
distribution among 75 HIV-infected documented sinusitis. j; = mean.
pa-
the four had both clinical and radiographic resolution. Sinus cultures were obtained from a total of four patients. cy-Hemolytic Streptococcus was found in three of the four, although never as the sole pathogen. Coagulase-negative Staphylococcus was cultured from two patients, one of whom also had Veillonella parvula cultured. Multiple organisms were cultured from one patient, including Mycobacteriurn avium complex (MAC), Haemophilus influenzae, Corynebacterium species, Citrobacter diversus, Proteus mirabilis, and Propionibacterium acnes. This patient also had disseminated MAC. Figure 2 shows the CD4 counts for the entire group of patients with sinusitis. Thirty-two (43%) had CD4 counts less than or equal to 196 celWmm3, while 16 had CD4 counts greater than 500/mm3. Outcome In terms of the clinical outcome of symptomatic patients, symptoms resolved in 23 patients (46%), persisted in five patients (lo%), and were of uncertain outcome in 22 patients (44%). Radiographic abnormalities improved or resolved in 13 patients (17%), were unchanged in 13 patients (17%), became worse in nine patients (12%), and recurred in one patient (1%). No follow-up radiographs were obtained in 39 patients (52%). The mean time of follow-up for the entire group from the time of the first radiographic evidence of sinusitis was 8.5 months (range: 0 to 38 months). Among the 13 patients with radiographic improvement, clinical resolution of symptoms was noted in 11. Antibiotics did not appear to affect the clinical outcome but may have had a role in hastening radiologic improvement. Fifteen of 18 patients (83%) with adequate follow-up who received antibiotics had resolution of symptoms as did nine of 11 pa160
August 1992 The American Journal of Medlclne
tients (82%) who did not receive antibiotics. Radiographically, nine of the 12 patients (75%) with follow-up radiographs who received antibiotics had radiographic improvement, while only four of 11 patients (36%) who did not receive antibiotics improved radiographically. Eight of the nine patients with radiographic improvement also improved clinically. For the 19 patients who were asymptomatic despite radiographic evidence of sinus disease, the mean follow-up was 8.7 months (range: 1 to 27 months). There were follow-up radiographs for four. Three of the follow-up films were unchanged, while one showed improvement. Eighteen of the 19 patients remained asymptomatic. One patient developed frontal headaches; his follow-up radiograph remained unchanged. For the six patients with radiographic evidence of sinus disease seen in radiographs ordered specifically to evaluate the sinuses (sinus series, sinus CT) but whose medical records did not document sinusrelated symptoms, two had follow-up radiographs. One showed minimal progression of radiographic abnormalities and the other revealed marked worsening that correlated with the development of fever and headaches. The remaining five patients remained asymptomatic. COMMENTS In the present study, we have retrospectively evaluated sinusitis in patients with HIV-l infection and found it to be common. However, as with any retrospective study, there are a few caveats that must be considered. First, we chose to define sinusitis radiographically as an objective means of identifying our study population, since there appeared to be no satisfactory objective clinical criteria by which patients could be retrospectively selected for inclusion. For some patients, particularly those for whom no sinus-related symptoms were described in the medical record and for whom radiographs revealed only mild chronic disease, the clinical significance of the radiographic findings may be suspect. This is especially true for patients whose only imaging study was an MRI scan of the head (n = 21; two with symptoms, 19 without). For six of these patients, only mild ethmoid disease was observed and all were asymptomatic. An age-matched control group of non-HIV-infected patients who had MRI scans of the head was not available. Since the mean follow-up period for these patients was relatively short and since they were not specifically followed for sinus-related symptoms, it is conceivable that a substantial proportion would have developed sinus disease at a later time, particularly those with abnormalities involving multiple sinuses. It is also
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possible that for sinus evaluation, MRI lacks adequate specificity in an asymptomatic population. Second,although a list of pertinent clinical symptoms of sinus diseasewaschosenprior to reviewing the medical records,it was not alwayscertain that the symptoms recordedin the medical record were in fact secondary to underlying sinusitis. Headaches,for instance,may have had other causes.If symptoms were believed by the examining physician to be related to a nonsinus cause,they were discounted. However, if symptoms could not be ruled out as being sinus-related,they were included. This may have resulted in overinclusivenessin our symptom list. Also, the clinical outcome was sometimesdifficult to determine. Very often, even for patients who were treated with antimicrobial agentsfor presumedsinus infection, little or no specific comment was made as to the clinical outcome in subsequentnotes.Since we did not construethe lack of documentation asa goodclinical response,a large percentageof our patient group werejudged by us to have an uncertain clinical outcome. Similarly, it could not always be ascertained whether patients were treated for their sinus disease.Since our patient population is entirely referral-based,it is likely that patients who may have developedsymptomatic sinusitis outside the NIH would have been treated by their referring physicians. Therefore, our data are likely to underestimate the true incidence of symptomatic sinus diseasein our population as well asthe true frequency of treatment with both decongestants and antibiotics. Given those limitations, much can be gleaned from our data. Sinusitis appearsto occur with significant frequencyin patients with HIV-l infection. Like sinusitis in non-HIV-infected patients, the maxillary sinuses were moat commonly involved [lo]. The paranasal sinusesmay be an important site of occult fever in this patient group given the fact that fever was the only symptom in five of the 24 patients with fever. Our data suggestthat the incidence of sinus disease increasesas the CD4 count declines,as is true of many infections in the setting of HIV-l disease[ll]. Sinceour patient population is highly selected,and since no systematic prospectivemeansto identify sinusitis in the group was used, it is difficult to derive meaningful incidenceestimates from our data. Other than low CD4 count, we did not identify any other obvious risk factors for sinusitis. A prior history of sinusitis was elicited from only eight patients. Interpretation of such a history is difficult consideringthat many patients claim to have a history of sinus diseaseor sinus symptoms without radiographicor clinical documentation.A history of
intranasal cocaineabusewas similarly difficult to interpret retrospectivelysincefrequencyand duration of cocaineusewere generallynot documented and since such a history was uncertain for 21 patients. It is intriguing to speculate as to the etiologic mechanism(s)underlying sinusitis in HIV-infected patients. A defect in humoral immunity may be important. HIV-infected patients are known to havehumoral immune dysfunction with polyclonal hypergammaglobulinemiaand defective antibody production in responseto specificantigens [12-141. It has also been well describedthat other patients with humoral immunodeficiency disordershaverecurrent sinus and pulmonary infections, typically secondaryto encapsulatedbacterialpathogenssuch as H. influenzae and Streptococcus pneumoniae [15,16].These pathogenshave also been described anecdotally to causesinusitis in HIV-infected patients. The same organismshave been reported to account for up to 10%of bacterial pneumoniasin this population [17]. One must also consider the possibility that nonbacterialpathogens,particularly respiratoryviruses,herpesviruses,or evenHIV-l itself, may be important etiologic agents.Finally, impaired sinus drainagesecondaryto lymphoid hyperplasiaor nonspecificmucosalinflammation may be contributory factors. In summary, our data indicate that sinusitis is a frequent problem occurring in patients with HIV-l infection, likely related to declining immunocompetence.Prospectivestudies should be undertaken to determine: (1) the true incidenceof sinusitis in HIV-infected patients; (2) the preciseassociationof sinusitis with declining immunocompetence;(3) the microbiologic etiology of infection; (4) the proper duration of antimicrobial therapy; and (5) the role of surgical intervention. ACKNOWLEDGMENT We thank Dr. Michael Polis for his valuable suggestions statistical considerations for this manuscript.
as regards editorial and
REFERENCES 1. Klein RS, Harris CA, Small CB, Mall B, Lesser M. Friedland GH. Oral candidiasis
in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N Engl J Med 1984; 311: 354-8. 2. Centers for Disease Control. Oral viral lesion (hairy leukoplakia) associated with acquired immunodeficiency syndrome. MMWR 1985; 34: 54940. 3. Quinnan GV Jr, Masur H, Rook AH, et a/. Herpesvirus infections in the acquired immune deficiency syndrome. JAMA 1984; 252: 72-7. 4. Marcusen DC, Sooy CD. Otolaryngologic and head and neck manifestations of acquired immunodeficiency syndrome (AIDS). Laryngoscope 1985; 95: 401-5. 5. Poole MD, Postma D, Cohen MS. Pyogenic otorhinologic infections in acquired immune deficiency syndrome. Arch Otolaryngol 1984; 110: 130-l. 6. Lim DT, Enright T, Shetty R, Park L. Asthma, recurrent sinopulmonary disease and HIV infection. Ann Allergy 1988; 61: 175-6. 7. Durrani FK, Church JA. Chronic otitis media/sinusitis as presenting infection
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SINUSITIS IN HIV-l INFECTION / ZURLO ET AL in pediatric AIDS [abstract]. Ann Allergy 1986; 56: 516. 8. Lamprecht J, Wiedbrauck C. Sinusitis and other typical ENT diseases within the scope of acquired immunologic deficiency syndrome (AIDS). HNO (Berlin) 1988; 36: 489-92. 9. Fineman DS. Palestro CJ. Kim CK, eta/. Detection of abnormalities in febrile AIDS patients with In-l 1 l-labeled leukocyte and Ga-67 scintigraphy. Radiology 1989; 170: 677-80. 10. Gwaltney JM Jr. Sinusitis. In: Mandell GL, Douglas RG. Bennett JE, editors. Principles and practice of infectious diseases. New York: Churchill Livingstone. 1990: 510-4. 11. Masur H. Ognibane FP. Yarchoan R. et a/. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann Intern Med 1989: 111: 223-31. 12. Lane HC, Masur H. Edgar LC. et al. Abnormaliiies of B-cell activation and
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immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983; 3091 453-8. 13. Chess Q, Daniels J. North E, et a/. Serum immunoglobulin elevations in the acquired immunodeficiency syndrome (AIDS): IgG, IgA, IgM. and IgD. Diagn lmmunol 1984; 2: 148-53. 14. Pahwa SG, Quilop MTJ. Lange M, et a/. Defective B-lymphocyte function in homosexual men in relation to the acquired immunodeficiency syndrome. Ann Intern Med 1984; 101: 757-63. 15. Hermans PE, Diaz-Buxo JA. Stobo JD. Idiopathic late onset immunoglobulin deficiency. Clinical observations in 50 patients. Am J Med 1976; 61: 221-32. 18. Lederman HM. Winkelstein JA. X-linked agammagfobulinemia: an analysis of 96 patients. Medicine (Baftimore) 1985; 641 145-56. 17. Polsky B. Gold JW. Whimbey E, et a/. Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986; 104: 38-43.
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