Rhinoscleroma

The Polish surgeon Johann von Mikulich in Wroclaw described the histologic features in 1877; von Frisch identified the organism in 1882. In 1932, Belinov proposed the use of the term scleroma respiratorium because the pathologic process in rhinosclerosis may involve not only the upper airways but also the lower airways. In 1961, Steffen and Smith demonstrated that K rhinoscleromatis conformed to Koch's postulates and that it was an etiologic factor in the inflammatory changes typical of scleroma. The occurrence of familial disease suggests that genetic control of the host response to K rhinoscleromatis may be an important factor in endemic areas.[1] Rhinoscleroma is a chronic infectious disease of underdeveloped countries.[2]

Rhinoscleroma is contracted by means of the direct inhalation of droplets or contaminated material. The disease probably begins in areas of epithelial transition such as the vestibule of the nose, the subglottic area of the larynx, or the area between the nasopharynx and oropharynx. Cellular immunity is impaired in patients with rhinoscleroma; however, their humoral immunity is preserved.

The CD4/CD8 cell ratio in the lesion is altered with decreased levels of CD4 lymphocytes; this change possibly induces a diminished T-cell response. Macrophages are not fully activated. Mucopolysaccharides in the bacterial capsule probably contribute to the inhibition of phagocytosis. The type K3 capsule of K rhinoscleromatis serves as a virulence factor.[3] Otherwise, patients are immunocompetent in every regard except for the ineffective phagocytosis of the organism by the Mikulicz cells.

Rhinoscleroma usually affects the nasal cavity, but lesions associated with rhinoscleroma may also affect the larynx; nasopharynx; oral cavity; paranasal sinuses; or soft tissues of the lips, nose, trachea, and bronchi. Rhinoscleroma may be evident as a tumor extruded from the mucosal lining of the upper lip.[4] It may also appear on the penis, where its presence may suggest a penile cancer.[5]  

Although it is usually caused by K pneumoniae subsp rhinoscleromatis, K pneumoniae subsp ozaenae was isolated from the pharynx of a woman with laryngeal scleroma.[6]

A Mexican study showed that DQA1*03011-DQB1*0301 haplotype is a strong risk factor for its development.[7]

A murine model has been described delineating Mikulicz cells as interleukin 10–dependent derivatives of inflammatory monocytes.[8]

Rhinoscleroma is caused by the gram-negative coccobacillus K rhinoscleromatis. Although crowded conditions, poor hygiene, and poor nutrition appear to be necessary for transmission of the infectious agent, the actual pathogenesis of infection remains elusive.

Frequency

It is endemic to poor regions of Africa (Egypt, tropical areas), Southeast Asia, Mexico, Central and South America, and Central and Eastern Europe, but it has been infrequent in the United States.[9] Rhinoscleroma reportedly also is rare in Saudi Arabia and Bahrain.[10] Five percent of all cases occur in Africa.[11] However, with current trends in migration, the incidence of rhinoscleroma may be on the rise.[12] The incidence of rhinoscleroma appears to be increasing in the United States. Rare sporadic cases occur in the United States, usually in immigrant populations arriving from the countries in which the disease is endemic. Rhinoscleroma is endemic to areas of Africa (Egypt, tropical areas), Southeast Asia, Mexico, Central and South America, and Central and Eastern Europe, with an increased incidence in Spain possibly due to new immigrants from endemic regions.[13] It is rare in Western Europe.[14]  In Egypt, its incidence seems to be decreasing, with clinical and histopathological patterns in less advanced forms, presumably owing to socioeconomic and treatment advances.[15]

Race

Patients of all races can be affected.

Sex

Rhinoscleroma tends to affect females somewhat more often than it does males.

Age

Typically, rhinoscleroma appears in patients aged 10-30 years.

The course is usually chronic. Relapses can occur. Despite antibiotic and surgical therapy, an incidence of recurrence in one series reached up to 25% within 10 years.[16] Rhinoscleroma is rarely lethal, unless it causes airway obstruction. The diagnosis may elude the clinician for years, and this delay can substantially increase the rate or severity of resultant morbidity.

Rhinoscleroma is rare chronic granulomatous infection that should be considered in patients from countries in which the disease is endemic if they have nasal polyps that significantly adhere to the nasal septum with relative sparing of the sinuses. Most often, the presentation is nonspecific. Because of its mundane clinical presentation resembling chronic rhinitis, it often goes unrecognized.[17] Chronic nasal infection caused by K rhinoscleromatis is often a misdiagnosed infectious disease.[18] Chronic rhinitis, even in developed countries, should prompt its consideration, especially because specific diagnostic tools and effective treatments are available. Recurrent epistaxis may be evident.[14] The pharynx, larynx, hard and soft palates, maxillary sinuses, and upper lip may be involved.[19, 20]

Note the following possible history findings:

• Nasal obstruction (most common complaint)

• Rhinorrhea

• Epistaxis

• Dysphagia

• Nasal deformity

• Anesthesia of the soft palate

• Difficulty breathing that progresses to stridor

• Dysphonia

• Anosmia

The initial nodule is often intra-nasal and small in size.[1] Rarely, if neglected, it can grow into an exophytic giant tumor, which may obstruct the entire respiratory tract.[21]  Rarely, rhinoscleroma of the nasal cavity may extrude into the oral cavity.[22] Rhinoscleroma may also extend into the orbit, to the base of the skull, and into the brain.[23] It may enter the brain through the cribriform plate.

Rhinoscleroma is a rare cause of upper airway obstruction. Isolated tracheal obstruction.[24, 25] Subglottal stenosis may be a late sequela of rhinoscleroma.[26] Scleroma is known to cause slowly progressive asphyxia.

A positive result with culturing in MacConkey agar is diagnostic of rhinoscleroma. However, culture results are positive in only 50-60% of patients.

Bacteria can be seen by using periodic acid-Schiff, Giemsa, Gram, and silver stains. A highly sensitive and specific method for identifying K rhinoscleromatis organisms is the analysis of a biopsy specimen with the immunoperoxidase technique.

CT findings in primary nasal and nasopharyngeal rhinoscleroma include soft-tissue masses of variable sizes. The lesions are characteristically homogeneous and nonenhancing, and they have distinct edge definition. Adjacent fascial planes are not invaded. The subglottic area is involved in laryngeal and tracheal scleroma. The lesions primarily cause concentric irregular narrowing of the airway. In the trachea, cryptlike irregularities are diagnostic of scleroma. Findings also include calcifications, luminal stenosis, wall thickening, and nodules.[33]  Radiological imaging facilitates distinction from other granulomatous and malignant disorders.[34]

In persons with pseudotumoral rhinoscleromas in the septum and in the rhinopharynx, respectively, CT scanning permitted a precise evaluation of the extent of the lesions.

MRI should be performed in patients with rhinoscleroma. Nasal masses can obstruct the ostiomeatal units, and secretions may be retained in the related sinuses. In the hypertrophic stage of rhinoscleroma, both T1- and T2-weighted images show characteristic mild-to-marked high signal intensity.

The cytological features include a lymphoplasmacytic inflammatory infiltrate admixed with classical Mikulicz cells.[35]

Diagnosis is facilitated by the use of cytologic methods that are easy to perform and do not cause pain in the patient (see Further Outpatient Care). Cytologic analysis is performed on brushing specimens of a lesion.[36] The characteristic cells of the Mikulicz type may be observed in the smear.

This chronic infectious disease of the upper respiratory tract is routinely diagnosed by means of tissue biopsy of the lesions.

Nasal endoscopy reveals signs of all 3 stages of scleroma: catarrhal, granulomatous, and sclerotic.

Bronchoscopy has a role in the early diagnosis of rhinoscleroma.[37]

Histopathologic analysis has a definite role in the diagnosis of rhinoscleroma. Classic histopathologic findings include large vacuolated Mikulicz cells and transformed plasma cells with Russell bodies. The Mikulicz cell is a large macrophage with clear cytoplasm that contains the bacilli; this cell is specific to the lesions in rhinoscleroma. The disease is most commonly diagnosed during the proliferative phase, in which the clinical and histologic presentations are most easily recognized.

The histologic findings correspond to the 3 clinical stages. In the catarrhal (or atrophic) stage, squamous metaplasia and a nonspecific subepithelial infiltrate of polymorphonuclear leukocytes with granulation tissue are observed. In the granulomatous stage, the diagnostic features include chronic inflammatory cells, Russell bodies, pseudoepitheliomatous hyperplasia, and groups of large vacuolated histiocytes that contain K rhinoscleromatis organisms (Mikulicz cells). If numerous, these bacteria can be seen with hematoxylin and eosin staining, but periodic acid-Schiff, silver impregnation, or immunohistochemical staining may be required to confirm their presence and identity. In the sclerotic stage, extensive fibrosis may lead to stenosis and disfiguration.

Microscopically, the connective tissue is highly vascular, with an inflammatory infiltrate consisting primarily of plasma cells and lymphocytes and a possible sprinkling of eosinophils. Russell bodies in the plasma cells are common. However, the groups, clusters, or sheets of large (100- to 200-μ m) vacuolated histiocytes (ie, Mikulicz cells) that contain the causative agent are most striking. Although the organisms are occasionally visible on standard hematoxylin and eosin stains, they are more readily demonstrated by using silver impregnation Warthin-Starry stains. The exudative stage results in a dense nonspecific fibrosis. In the exudative and cicatricial stages, Mikulicz cells may be difficult to detect. When no Mikulicz cells are evident, one looks for a heavy plasma cell infiltration without eosinophils.[38]

Electron microscopy reveals large phagosomes filled with bacilli and surrounded by a finely granular or fibrillar material that is arranged in a radial pattern. This finding represents the accumulation of antibodies on the bacterial surface (type A granules), as well as the aggregation of bacterial mucopolysaccharides surrounded by antibodies (type B granules).

See the image below.

Very high magnification micrograph of rhinoscleroma. Hematoxylin and eosin stain. Silver staining demonstrates the presence of microorganisms consistent with Klebsiella rhinoscleromatis. Courtesy of Nephron (own work), via Wikimedia Commons.

Bronchoscopy has a role in the initial treatment of symptoms. Treatment should also include long-term antimicrobial therapy and surgical intervention in patients with symptoms of obstruction.

Bacterial overinfection responds to treatment with third-generation cephalosporins and clindamycin. Sclerotic lesions respond well to treatment with ciprofloxacin. Long-term antibiotic therapy often eradicates this infection.[39]

The choice of long-term antibiotic therapy should be guided by the patient's age and sex. Repeat biopsy can be performed to help determine the appropriate duration of the antibiotic therapy.

Surgery combined with antibiotic therapy is beneficial in patients with granulomatous disease and nasal or pharyngeal obstruction or nasal sinus involvement due to the proliferation of lesions. Rhinoplasty may be effective for external nasal deformities.[40]

Tracheotomy should be considered in patients with laryngeal obstruction of the second degree (granulomatous stage) and above (sclerotic stage).

Plastic surgery is necessary in patients with cicatricial stenosis or when imperforation remains in the nasal cavity, pharynx, larynx, or trachea.[41]

Extensive granulomatous lesions are treated by means of open excision by using the laryngofissure approach, which is the best method for a quick recovery in patients without evidence of subglottic stenosis.

Surgery and laser therapy are required to treat airway compromise and tissue deformity. Fiberoptic intubation[42] allows assessment of the pathology and subsequent passage of a cuffed tracheal tube to secure the airway. To overcome respiratory obstruction as the fiberscope passes through the opening in the membrane, either rapid intubation or a technique of preoxygenation and voluntary hyperventilation followed by breath holding during bronchoscopy is used. The thin caliber and maneuverability of the flexible fiberoptic bronchoscope makes fiberoptic intubation an excellent technique for airway management in cicatricial membranes of the pharynx.

Treatment of the advanced cicatrix with carbon dioxide laser vaporization yields excellent results. Obstructive lesions of the larynx and subglottic space are always a challenging problem for the endoscopist and anesthetist. At this level of the obstruction, the effectiveness and innocuous nature of carbon dioxide laser treatment are related to the degree of endoscopic exposure. Because of the transtracheal high-frequency jet ventilator, ensuring a free laryngeal endoscopic operative field is now possible.

The transtracheal catheter is introduced percutaneously through the cricothyroid membrane into the trachea under endoscopic control and connected to a high-frequency jet ventilator. Among many advantages of this technique, the most convincing include a clear operating field for the surgeon, complete relaxation of the patient, good respiratory gas exchange, elimination of the risk of igniting an endotracheal tube with the laser, decrease in the risk of aspiration of blood and debris, and the ability to provide oxygen and/or mechanical ventilation in the postoperative period.

Palatal symptoms may be relieved by means of uvulopalatopharyngoplasty.

Consultation with a plastic surgeon may be helpful in patients with cicatricial stenosis or in those with imperforation of the nasal cavity, pharynx, larynx, or trachea. An endoscopist and an anesthetist may be required to perform vaporization with a carbon dioxide laser.

Owing to the high rate of recurrence, prolonged antibiotic therapy (months to years) is necessary.

Nasal cytology is an easy and noninvasive investigation. This method can be performed on an outpatient basis as an adjuvant to clinical and histopathologic studies, along with nasal endoscopy. Nasal cytology is a simple, reliable, and timesaving procedure that can be used with further therapy.

Bronchoscopy plays a role in the follow-up care of patients.

Relapses occur, and close observation is the key to the long-term follow-up care of the patient.

Class Summary

Tetracycline is the drug of choice. Other antibiotics include ciprofloxacin and rifampin. Bacterial overinfection responds to treatment with clindamycin and third-generation cephalosporins. Sclerotic lesions respond well to treatment with ciprofloxacin. Ciprofloxacin has the following advantages: Its oral administration is convenient, it achieves good tissue penetration, it is concentrated in macrophages, and it may prove useful in the treatment of patients with rhinoscleroma.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone with activity against Pseudomonas species, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, growth. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.

Cefixime (Suprax)

Cefixime is a third-generation cephalosporin. It arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more penicillin-binding proteins.

Rifampin (Rifadin, Rimactane)

Rifampin inhibits DNA-dependent bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription.

Clindamycin (Cleocin)

Clindamycin is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes and causing the arrest of RNA-dependent protein synthesis.

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Meticorten, Orasone)

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.