AMP case report: Rhinoscleroma in Southern California—diagnosis made by multidisciplinary investigation

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Prior to the wide availability of genetic testing, K. rhinoscleromatis was identified by special immunologic and serologic methods, which are not widely available.^9,10 Although histopathological exams can provide important clues (e.g. Milulicz cells and Gram-negative bacilli) to support a diagnosis of rhinoscleroma, these positive findings lack specificity and may not be readily recognized. In terms of molecular testing, our study revealed 16S rRNA sequence alone, even full length, is not sufficient to differentiate K. pneumoniae subsp. rhinoscleromatis from highly genetically related K. variicola, K. quasipneumoniae, and the rest of K. pneumoniae subspecies in the K. pneumoniae complex. Additional genes such as rpoB and groEL must be analyzed. Therefore, the current commercially available sequencing tests and services for pan-bacterial identification using 16S rRNA are not able to identify this organism. WGS-based phylogenetic analysis such as k-mer tree provide the highest resolution to confirm the identification. As next-generation sequencing becomes more widely available in clinical laboratories, it represents a powerful tool in identifying rare and challenging organisms.¹

Fig. 3. K-mer tree clustering of several species and subspecies in the K. pneumoniae (Kp) complex including K. quasipneumoniae, K. variicola, and K. pneumoniae subsp. pneumoniae and subsp. rhinoscleromatis. The NCBI accession number for each reference species/subspecies is shown. The patient’s isolate is shown (red box) to cluster closely with K. pneumoniae subsp. rhinoscleromatis. The scale bar indicates the genetic distance of the branch length in the k-mer tree.

Conclusion. Rhinoscleroma caused by K. pneumoniae subsp. rhinoscleromatis is extremely rare in nonendemic areas including the United States. The previous case reported in the U.S. was caused by the rarer K. pneumoniae subsp. ozaenae,³ and similar to our patient, that patient had immigrated to the U.S. from Mexico and had longstanding symptoms. Based on histopathological diagnosis, our patient was likely in the second stage of the disease with many Mikulicz cells. Histopathological diagnosis was confirmed by microbiological results and high-resolution genomic characterization. Definitive diagnosis of infection with K. pneumoniae subsp. rhinoscleromatis is challenging because of the rarity of the infection and the limitation of conventional microbiological testing methods. This case highlights the value and strength of multidisciplinary collaboration including surgical pathology, conventional microbiology, and molecular microbiology for a timely and accurate diagnosis of a rare infection such as rhinoscleroma.

1. Price TK, Realegeno S, Mirasol R, et al. Validation, implementation, and clinical utility of whole genome sequencing-based bacterial identification in the clinical microbiology laboratory. J Mol Diagn. 2021;23(11):1468–1477.
2. Umphress B, Raparia K. Rhinoscleroma. Arch Pathol Lab Med. 2018;142(12):1533–1536.
3. Gonzales Zamora J, Murali AR. Rhinoscleroma with pharyngolaryngeal involvement caused by Klebsiella ozaenae. Case Rep Infect Dis. Epub May 12, 2016. doi:10.1155/2016/6536275.
4. de Pontual L, Ovetchkine P, Rodriguez D, et al. Rhinoscleroma: a French national retrospective study of epidemiological and clinical features. Clin Infect Dis. 2008;47(11):1396–1402.
5. Mukara BK, Munyarugamba P, Dazert S, Löhler J. Rhinoscleroma: a case series report and review of the literature. Eur Arch Otorhinolaryngol. 2014;271(7):1851–1856.
6. Casanova JL, Abel L. Human genetics of infectious diseases: a unified theory. EMBO J. 2007;26(4):915–922.
7. Chan TV, Spiegel JH. Klebsiella rhinoscleromatis of the membranous nasal septum. J Laryngol Otol. 2007;121(10):998–1002.
8. Bonacina E, Chianura L, Sberna M, et al. Rhinoscleroma in an immigrant from Egypt: a case report. J Travel Med. 2012;19(6):387–390.
9. Botelho-Nevers E, Gouriet F, Lepidi H, et al. Chronic nasal infection caused by Klebsiella rhinoscleromatis or Klebsiella ozaenae: two forgotten infectious diseases. Int J Infect Dis. 2007;11(5):423–429.
10. Amoils CP, Shindo ML. Laryngotracheal manifestations of rhinoscleroma. Ann Otol Rhinol Laryngol. 1996;105(5):336–340.

Dr. Kamau, Dr. Narasumhalu, Dr. Garner, Dr. Goldstein, and Dr. Yang are in the Department of Pathology and Laboratory Medicine; and Dr. Mendelsohn is in the Department of Head and Neck Surgery—all in the David Geffen School of Medicine, University of California, Los Angeles.

Test yourself

Here are three questions taken from the case report.

1. What are the three clinical progressive stages (in sequence from 1–3) of rhinoscleroma infection?
a. Catarrhal-atrophic stage, sclerotic/fibrotic stage, granulomatous stage.
b. Granulomatous stage, catarrhal-atrophic stage, sclerotic/fibrotic stage.
c. Sclerotic/fibrotic stage, catarrhal-atrophic stage, granulomatous stage.
d. Granulomatous stage, sclerotic/fibrotic stage, catarrhal-atrophic stage.
e. Catarrhal-atrophic stage, granulomatous stage, sclerotic/fibrotic stage

2. Of the three clinical progressive stages of rhinoscleroma infection, which one is characterized by the presence of Mikulicz cells?
a. Catarrhal-atrophic stage.
b. Sclerotic/fibrotic stage.
c. Granulomatous stage.
d. None of the above.
e. All of the above.

3. Which of the following methods can definitively identify K. pneumoniae subsp. rhinoscleromatis?
a. MALDI-TOF MS.
b. Conventional biochemical reactions.
c. 16S rRNA gene sequencing alone.
d. Whole genome sequencing.
e. All of the above.

Answers are online now at www.amp.org/casereports and will be published next month in CAP TODAY.