212
KLEBSIELLA RHINOSCLEROMATIS: A CLINICAL AND PATHOGENIC ENIGMA ROBERT H. MILLER, MD BY INVITATION
HOUSTON, TEXAS JOEL B. SHULMAN, MD BEVERLY HILLS, CALIFORNIA RINALDO F. CANALIS, MD TORRANCE, CALIFORNIA PAUL H. WARD, MD LOS ANGELES. CALIFORNIA Rhinoscleroma is a chronic, slowly progressive, Infectious dise~ of the respiratory tract that can produce disability and death, if untreated. Once considered an anomaly In the United States, the dlse~ Is now seen more frequently In this country, owing to Increased travel from endemic areas. This report presents a comprehensive review of the several types of therapy that have been published In the literature. The results of a clinical experiment are also presented.
FIRST described as a sarcoma in 1670 by von Hebra.' rhinoscleroma was later identified by Geber (1672) and Mikulicz (1676)2 as an inflammatory process. In 1862, von Frisch? described the bacillus then presumed to be responsible for the disease. Half a century later, the 1932 International Congress of Otolaryngology recommended changing the name of the disease to scleroma, thus emphasizing the fact that the disease could affect extraSubmilled for publication Sept 11, 1978. From the Department of Surgery, Division of Head and Neck Surgery, UCLA School of Medicine, Los Angeles. Dr Miller is now with the Baylor College of Medicine, Houston. Presented as a Scientific Poster Presentation at the Annual Meeting of the Americ'ln Academy of Otolaryngology, Las Vegas, Sept 10-13. Reprint requests to Baylor College of Medicine, Department ofOtorhinolaryngology and Communicative Sciences, Houston, TX 77030 (Dr Miller). 1978
nasal sites in the respiratory tract. Nevertheless, since the nasal mucosa is the primary site of involvement, the original name is still commonly used. CLINICAL FEATURES Endemic in eastern Europe, the Middle East, and some areas of Central and South America, rhinoscleroma was previously considered a rare disease in the United States. Now that travel from Central and South America, as well as from other endemic areas, has increased, the disease is seen more frequently in this country. Rhinoscleroma is characterized by variable symptoms (Table 1). Granular erythematous and edematous swellings with overlying crusts of the mucous membranes of the nose are the typical presenting symptoms. The granulation may be sufficient to suggest tumor formation, which, combined with the crusting, reduces the airway to the point of obstruction. Involvement of nasal, laryngeal, and sinus mucosa with accompanying disfigurement is seen in advanced cases. Tissue destruction and scarring distort the external nasal, as well as the Internal nasopharyngeal anatomy, and acute laryngeal and tracheal involvement can produce sufficient obstruction to require tracheotomy. With or without therapy, healing
Otolaryngol Head Neck Surg 87:212-221 (Mar-Apr) 1979 Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
213
KLEBSIELLA RHINOSClEROMATIS TABLE 1 FREQUENCY OF INITIAL SYMPTOMS OF RHINOSCLEROMA, DETERMINED BY REVIEW OF LITERATURE SYMPTOM
Nasal obstruction Nasaldeformity Hoarseness Epistax is Upper lip swelling Sore throat Epiphora
fREQUENCY ('/.)
94 32 12 11 10 6 4
causes scarring and a uniquely characteristic anterior glottic webbing and subglottic scarring (Fig 1). Death may occur as a result of airway obstruction, hemorrhage, or intracranial extension. Rhinoscleroma is spread during its active stages by direct or indirect contact with persons who have clinical and subclinical diseases.' Close contact in confined areas in unhygienic conditions tends to increase the chance of infection. Three stages have been described, although they represent artificial subdivisions in which signs and symptoms frequently overlap. The first, or rhinitic, stage is most often characterized by a mucopurulent discharge from the nose. Biopsy specimens usually reveal nonspecific inflammatory response. The second, or florid, stage is distinguished by a granulomatous reaction and tissue distortion, and the third, or fibrotic, stage exhibits spontaneous or therapeutic resolution of the disease, with scarring leading to anatomic distortion. The frequency of involvement of different areas is shown in Table 2. The presumed (Koch's postulate not fulfilled) etiologic agent, Klebsiella rhinoscleromatis (von Frisch bacillus), is a short, gram-negative rod, which is best cultured from a homogenate of affected tissue obtained by biopsy. Agglutination
Fig 1.-Rhinoscleroma of larynx. Note anterior webbing.
TABLE
2
APPROXIMATE FREQUENCY OF SITES INVOLVED IN RHINOSCLEROMA, DETERMINED BY REVIEW OF LITERATURE SITE
FREQUENCY ('/0)
95
Nose Palate Pharynx
31 18 14 12
Larynx Upper lip Paranasal sinuses Lacrimal sac Trachea Orbit
4
4 2 1
and intradermal skin tests are also available, but they are of equivocal value.' A more specific, complement fixation test has greater reliability and has proved helpful in determining the effectiveness of therapy.! PATHOLOGY
In the init ial rhinitic, inflammatory stages of the disease, biopsy specimens may demonstrate only nonspecific inflammatory change; but, during the florid phase, the overlying nasal mucosa may become atrophic or hyperplastic. There is
Oro/aryngol Head Neck Surg 87:212-221 (Mar-Apr) 1979 Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
214
MILLER ET AL
a profuse subepithelial inflammatory infiltrate consisting mostly of clusters of plasma cells, fibroblasts, and large, vacuolated MikuJicz cells containing short intracellular gram-negative rods, which are pathognomonic of this disease (Fig 2). Lymphocytes and occasional polymorphonuclear leukocytes may also be identified in these infiltrates along with varying degrees of fibrosis. It is believed that elliptic enucleate formations with homogeneous cytoplasm occur within plasma cells, and when the cells degenerate, these formations are extruded as a result, becoming Russell bodies. The origin of the foamy Mikulicz cells is controversial: some evidence supports the hypothesis that the cells are derived from plasma cells,6 but a larger number of investiga-
tors believe the cells arise from hlstiocytes behaving as macrophages, as noted by l. Zamboni, MD (verbal communication, August 1978). Periodic acid-Schiff (PAS) staining facilitates demonstration of the gram-negative bacillary forms contained with in cytoplasmic vacuoles (Fig 3).
light and electron microscopic studies have disclosed several important findings relating to the pathogenesis of rhinoscleroma (Zamboni). Polymorphonuclear leukocytes actively phagocytize the bacilli as the bacilli enter the nasal mucosa. These cells then degenerate, either disintegrating or being engulfed by typical histiocytes and Mikulicz cells present in the stoma.
FIB 2.-Mlkullcz cells lhematoxylln-eosln, X100).
Oto/aryngol Head Neck Surg 87:212·221 (Mar-Apr) 1979 Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
KLEBSIELLA RHINOSCLEROMATIS
215
Fig 3.-lnlracellular bacilli (periodic acid-Schiff Slain, X430).
Mikulicz cells envelop large quantities of organisms, retaining them within phagocytic vacuoles (Fig 4). As these cells incorporate increasing numbers of bacilli, they become so swollen that the membranes rupture and release these organisms. Zamboni has demonstrated dividing rhinoscleroma organisms within Mikulicz cells of patients undergoing therapy and noted that these bacilli, when liberated, appear morphologically viable (Fig 5).
TREATMENT Various antibiotics have been used to treat rhinoscleroma, but streptomycin has probably been prescribed more often than any other drug. 7.'o Tetracycline,'1.13
chlorarnphentcol,i- and kanamycin sulfate,1S have also successfully been used. Sulfonamides and penicillins have proved ineffective. One patient treated in this series presented responded well to cephalexin. Several of the patients had been treated with other drugs prior to this series. In cases of selected, isolated lesions, Shaw and Martin 3 recommended radical surgical resection of circumscribed lesions. A summary of the cases seen in this series appears In Table 3. The therapeutic success achieved with tetracycline is exemplified in the following case reports. One of the patients also participated in an experiment to assess the effectiveness
Oto/aryngof Head Neck Surg 87:212-221 (Mar-Apr) 1979 Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
216
MILLER ET AL
Fig ".-K/ebs/ellil rhlnoscleromilfls within vacuole of Mlkulicz cell (X8,700).
of surgical treatment compared with that of medical therapy. The experiment involved resecting the tissue on one side while using the opposite side as a control.
lation tissue , crusting, and induration were bilaterally present in the nasal cavities. Small mucosal nodules were noted on the posterior oropharyngeal wall. The left lacrimal sac was swollen and tense. Although indirect laryngoscopic examination revealed normal vocal cords, a narrow subglottic region was almost completely occluded by crusts.
CASE REPORTS
Routine admission laboratory test results were normal and chest radiographs indicated no evidence of disease . Sinus radiographs and tomographic examination showed cloudy maxillary antra and possible bone destruction of the left lateral nasal wall. After tracheostomy, direct laryngoscopy was performed. Biopsy specimens of granulation tissue from the nose, the oropharynx, and the subglottic region showed intracellular gram-negative organisms in "foamy cells" similar to those observed with
CASE 1.-A 25-year-old Mexican man had a five-year history of persistent bilateral nasal obstruction. mild Intermittent epistaxis, and purulent discharge. For one month, he had noted gradually progressive dyspnea and mild hoarseness. On physical examination, the patient was found to have moderate Inspiratory and expiratory stridor. Both nasal vestibules were narrowed, and exuberant, friable granu-
Oto/aryngol Head Neck Surg 87:212-221 (Mar-Apr) 1979 Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
KLEBSIELLA RHINOSCLEROMATIS
217
*
*
*
Fig 5.-Viable-appearing Klebsiella rhlnoscleromatis (asterisks) escaping through rupture of Mlkullcz cell membrane (arrows) (X21,OOO).
rhinoscleroma (Fig 2). Cultures of the tissue biopsy specimens grew K rhinoscleromatis microorganisms that were sensitive to several antibiotics, including streptomycin, tetracycline, cephalosporin, and doxycycline. A regimen of tetracycline, 2 gm/day, was prescribed, and after one month of treatment, all granulation tissue had disappeared, although intranasal and subglottic inflammation, as well as scarring, persisted along with troublesome crust formation. Subsequent nasal and subglottic biopsy specimens taken at this time, in addition to repeated cultures, failed to confirm the presence of K rhinoscleromatis, and the tracheostomy was thereafter allowed to close. A dacryocystorhinostomy was then performed for nasolacrimal duct obstruction secondary to scarring. Nine months after initiation ot treatment, a rash developed that disappeared when tetracycline was discontinued. In four weeks, nasal symptoms recurred and the patient was
placed on cephalexin, 2 gm/day for six months, after which the dosage was reduced to 1 gm/day for a similar period of time. At the time of writing, the patient has not had therapy for 2.5 years, and there is no evidence of relapse. CASE 2.-A 41-year-old Mexican man had a progressive nasal deformity. He had noted rhinorrhea and nasal stuHiness three years previously while working In the Yucatan peninsula, and a year after the onset of these symptoms, nasal swelling occurred, which caused him to seek medical advice . Treatment at that time with an undetermined oral antibiotic failed to produce any change. Four months before the man came to the United States for treatment, the nasal deformity grew, and at examination, the entire nasal pyramid was noticeably swollen (Fig 6, left). The vestibule was greatly narrowed, and the mucosa
Oto/aryngol Head Neck Surg 87:212-221 (Mar-Apr) 1979 Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
Downloaded from oto.sagepub.com at Purdue University on June 4, 2016
0
\0 ...... \0
-..
~
'tJ
:).
II>
~
.
""""-.. -..
I
-.. N
i-:,
......
Co>
OQ
c
VI
.
~
l"l
nl
2:
Q.
II>
nl
J:
~
-e ;:)
Ai
.
0
Nose. maxillary sinuses. nasopharynx; Lacrimal gland. subglottic space Nose
Nose. nasopharynx. larynx, trachea
Nasal obstruction, rhinorrhea, epistaxis: 4 yr
Hoarseness. dyspnea: 1 yr
5
6
Nose
Nose, maxillary sinus
Nose. oropharynx. palate
SITE OF INVOLVEMENT
Nasal obstruction. epistaxis, rhinorrhea: 5 yr; Hoarseness and dyspnea: 1 mo
Epistaxis: 2 wk
Nasal obstruction, rhinorrhea: several yr
Nasal obstruction: 8 yr
SYMPTOMS AND DURATION
4
3
2
1
PATIENT
3
+
Nonspecific granulation
+
+
+
+.
PATHOLOGIC CONDITION
SUMMARY OF CASESIN THIS SERIES
TABLE
Tetracycline
Tetracycline
+
Klebsiella (species not specified)
Tetracycline for 9 mo, then cephalexin
Tetracycline
Tetracycline
Tetracycline
TREATMENT
+
+
Not done
+
CULTURE
Good
Fair (patient did not take tetracycline regularly)
Good
Good
Good
Good
RESPONSE
~
>
-f
m
;lO
,.,.,
~ ~
~
N CD
...
KLEBSIELLA RHINOSCLEROMATIS
219
w
I
-0 0'-
.)I
] $ II>
~
.E
E
~
... ~ U-e ....... 0... 0
II> II>
l'f'\
III
>-
a.:
~