Return to: Sarcoidosis

Initiated 8/24/2022 by Aditi Katwala, Matthew Hoffman and Henry Hoffman

Case Example

Definitions

1. Sarcoidosis is an inflammatory disorder of unknown origin.
   • It is characterized by an infiltration of non-necrotizing granulomas, most commonly occurring in the lungs and thoracic lymph nodes (Wiegand and Brutsche 2006).
   • Disease can also affect the eyes, bones, skin, liver, spleen, heart, salivary glands, upper respiratory and nervous system.
2. Sarcoidosis may additionally afflect the larynx.
   • Usually manifests in the supraglottic area, such as the epiglottis, arytenoids, and aryepiglottic folds (Ahmadi 2019).
   • Most commonly without true vocal fold involvement.

Presentation

Patients with Laryngeal Sarcoidosis may present with chronic dyspnea, stridor, snoring, hoarseness, and/or dysphagia (Seve 2021).If left untreated, this disorder may lead severe airway obstruction (Edriss 2019).

Evaluation

• There is no single specific test for Laryngeal Sarcoidosis - it is generally a diagnosis of exclusion that relies on clinical/radiographic/histopath examination.
  • Flexible fiberoptic laryngoscopy in clinic may occassionally be done with biopsy if it can be done safely - and with cultures additionally to potentially help establish the diagnosis.
    • In the appropriate clinical context, nodular thickening around the epiglottis, arytenoids, and aryepiglottic folds are a strong indicator of Laryngeal Sarcoidosis (Edriss 2019).
    • Biopsy may more commonly be performed under general anesthesia with direct laryngoscopy to control the airway and manage potential bleeding
      • Cultures to test for fungal and mycobacterial infections; these infectious disorders are included in the differential diagnosis of granulomatous disease (although are more commonly caseating rather than the noncaseating that characterizes sarcoidosis) (Edriss 2019).
  • Radiographic
    • Chest radiography in all cases
    • PET and gallium scanning of questionable value - may useful in specfic cases
    • Other imaging studies based on organ involvement
  • Tissue biopsy
    • Noncaseating granulomas
    • If positive for noncaseating granuloma
      • Further w/u requires recognition that sarcoidosis is a systemic disease
      • In addition to organ-involvment consultations, needs cardiac and opthalmologic w/u
  • Lab
    • serum calcium
      • 10% of patients with sarcoidosis will have at least transient hypercalcemia; hypercalciuria more common (ref Parrish 2009)
      • macrophages in patients with sarcoidosis are capable of the hydroxylation that produces the active metabolite of vitamin D which is the likely causative factor for hypercalcemia (Sharma 1996)
    • urinalysis
    • liver enzymes
    • CBC
    • SACE (serum angiotensin converting enzyme) (ref Parrish 2009)
      • At one point thought to be diagnostic of sarcoidosis
      • Epithelioid cells of sarcoid granulomas produce serum angiotensin converting enzyme
      • Not thought to be sensitive/specific enough to be used as diagnostic tool
      • SACE also elevated:  diabetes mellitus, cirrhosis, acute hepatitis, chronic renal disease, silicosis, Gaucher's disease, leprosy, asbestosis, and berylliosis

Treatment

1. Treatment for LS includes intralesional injections, corticosteroids, and surgical excision with instruments or CO2 laser.
   • Can be performed in the operating room or office.
2. Targeted procedural treatment for laryngeal sarcoidosis
   • Intralesional injections and corticosteroids are reported as treatment regimens.
     • Hydroxychloroquine and methotrexate or azathioprine may be used (Edriss 2019).
     • Injections can be performed in the OR: Butler et al used varying doses of 40 to 120 mg of methylprednisolone acetate at a concentration of 40mg/ml to treat patients with LS.
       • The amount administered and exact dose per patient was determined based on the mucosal volume and lesion’s size, respectively.
       • Prior to OR treatment, the patients had been given 40 mg/d of prednisone.
     • Injections can be given in office: Farlow et al used 3.5 ml triamcinolone at a concentration of 40 mg/ml on a female patient with LS.
       • Injection site was locally anesthetized with 4% lidocaine spray.
       • Initial injection was followed with 5 monthly treatments until there was a significant reduction in granuloma size.
       • Patient followed up for additional bimonthly injections one year later due to recurrence.
3. Surgical interventions for Laryngeal sarcoidosis
   • Well circumscribed lesions can be excised using cold instruments (Edriss 2019).
   • Laser reduction: Butler et al followed intralesional injections with laser photoreduction using CO2 laser at continuous settings of 8 to 10W.
     1. This created a “Peper Pot” effect. (Butler 2010[HMR1] ).
4. Tracheostomy: About 15% of cases have complications that lead to the need for a tracheostomy (Duchemann 2014).

Collaboration

1. Consultation with other specialists is required
   • Chest x-ray and chest CT should be obtained and patient should be referred to pulmonology for further evaluation (Farlow 2021).
   • Sarcoidosis experts (may be Rheumatology or Pulmonary Medicine) should be consulted to evaluate for multi-system disease (Farlow 2021).
   • In case of involvement of the eyes, nervous system or other organ system, the physician should refer the patient to the appropriate specialist. 

References

Ahmadi, A., Dehghani Firouzabadi, F., Dehghani Firouzabadi, M., & Roomiani, M. (2019). Isolated laryngeal sarcoidosis. Respirology Case Reports, 8(1). https://doi.org/10.1002/rcr2.502

Bargagli, E., Prasse, A. Sarcoidosis: a review for the internist. Intern Emerg Med13, 325–331 (2018). https://doi-org.proxy.lib.uiowa.edu/10.1007/s11739-017-1778-6

Burke RR, Rybicki BA, Rao DS. Calcium and vitamin D in sarcoidosis: how to assess and manage. Semin Respir Crit Care Med. 2010 Aug;31(4):474-84. doi: 10.1055/s-0030-1262215. Epub 2010 Jul 27. PMID: 20665397; PMCID: PMC4876288.

Butler CR, Nouraei SA, Mace AD, Khalil S, Sandhu SK, Sandhu GS. Endoscopic airway management of laryngeal sarcoidosis. Arch Otolaryngol Head Neck Surg. 2010 Mar;136(3):251-5. doi: 10.1001/archoto.2010.16. PMID: 20231642.

Cereceda-Monteoliva N, Rouhani MJ, Maughan EF, Rotman A, Orban N, Al Yaghchi C, Sandhu G. Sarcoidosis of the ear, nose and throat: A review of the literature. Clin Otolaryngol. 2021 Sep;46(5):935-940. doi: 10.1111/coa.13814. Epub 2021 Jun 8. PMID: 34051056.

Duchemann B, Lavolé A, Naccache JM, Nunes H, Benzakin S, Lefevre M, Kambouchner M, Périé S, Valeyre D, Cadranel J. Laryngeal sarcoidosis: a case-control study. Sarcoidosis Vasc Diffuse Lung Dis. 2014 Oct 20;31(3):227-34. PMID: 25363223.

Edriss, John S Kelley, Joshua Demke, Kenneth Nugent, Sinonasal and Laryngeal Sarcoidosis—An Uncommon Presentation and Management Challenge. The American Journal of the Medical Sciences, Volume 357, Issue 2, 2019, Pages 93-102, ISSN 0002-9629, https://doi.org/10.1016/j.amjms.2018.11.007.

Farlow JL, Park JV, Morrison RJ, Kupfer RA. Office-Based Intralesional Steroid Injection for Treatment of Laryngeal Sarcoidosis. Ann Otol Rhinol Laryngol. 2021 Aug;130(8):976-979. doi: 10.1177/0003489421995287. Epub 2021 Feb 15. PMID: 33583192.

Kleiner R, Brutsche M. Sarkoidose--klinische Aspekte [Sarcoidosis--a multisystem disorder with variable prognosis]. Ther Umsch. 2016;73(1):31-5. German. doi: 10.1024/0040-5930/a000752. PMID: 26884218.

Sève, P.; Pacheco, Y.; Durupt, F.; Jamilloux, Y.; Gerfaud-Valentin, M.; Isaac, S.; Boussel, L.; Calender, A.; Androdias, G.; Valeyre, D.; El Jammal, T. Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis. Cells 2021, 10, 766. https://doi.org/10.3390/cells10040766

Strychowsky JE, Vargas SO, Cohen E, Vielman R, Son MB, Rahbar R. Laryngeal sarcoidosis: presentation and management in the pediatric population. Int J Pediatr Otorhinolaryngol. 2015 Sep;79(9):1382-7. doi: 10.1016/j.ijporl.2015.06.017. Epub 2015 Jun 25. PMID: 26148428.

Wiegand JA, Brutsche MH. Sarcoidosis is a multisystem disorder with variable prognosis--information for treating physicians. Swiss Med Wkly. 2006 Apr 1;136(13-14):203-9. PMID: 16633969.

Parrish S and Turner JF: "Diagnosis of Sarcoidosis"  Disease a Month Vol 55 Issue 11  2009

Sharma O.P.:  Vitamin D, calcium, and sarcoidosis.  Chest 109. 535-539.1996; 

Muller-Quernheim J, Schurmann M, Hoffmann S, Gaede KI, Fischer A, Prasse A, Zissel G, and Schreiber S: Genetics of Sarcoidosis. Clinics in Chest Medicine Vol 29, Issue 3 (Sept 2008)

Rybicki B.A., Major M., Popovich , Jr , JrJ., et al:  Racial differences in sarcoidosis incidence: a 5-year study in health maintenance organization.  Am J Epidemiol 145. 234-241.1997

Kobak S. Sarcoidosis: a rheumatologist's perspective. Ther Adv Musculoskelet Dis. 2015 Oct;7(5):196-205. doi: 10.1177/1759720X15591310. PMID: 26425148; PMCID: PMC4572362.

Katwala, Aditi et al. “Sarcoidosis manifesting as isolated nasal crusting and dysphonia.” Otolaryngology Case Reports (2023): n. pag.