Dysphagia (2015) 30:583–585 DOI 10.1007/s00455-015-9636-z
CLINICAL CONUNDRUM
Dysphagia Caused by Chronic Laryngeal Edema Alexander Delides1 • George Sakagiannis1 • Pavlos Maragoudakis1 • Alina-Roxani Gouloumi2 • Pelagia Katsimbri3 • Ioannis Giotakis1 • John G. Panayiotides2
Received: 15 May 2015 / Accepted: 30 June 2015 / Published online: 7 July 2015 Ó Springer Science+Business Media New York 2015
Abstract A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office. Keywords Deglutition Deglutition disorders Laryngeal edema Laryngeal diseases Sarcoidosis
Case Presentation A 39-year-old female living in a small isolated Greek island was admitted in our Department with a 4-month history of intermittent dyspnea, globus sensation, and severe swallowing difficulty affecting predominately solids. She was afebrile and did not complain for pain during swallowing. She had been visiting her family physician and was prescribed with antibiotics and oral steroids with no improvement. Her past medical history included tonsillectomy 8 years ago for recurrent tonsil infection. She was also investigated
& Alexander Delides [email protected] 1
2nd Otolaryngology Department, University of Athens Medical School, ‘‘Attikon’’ University Hospital, 1 Rimini St., Chaidari, 124 62 Athens, Greece
2
2nd Department of Pathology, University of Athens Medical School, ‘‘Attikon’’ University Hospital, Athens, Greece
3
Rheumatology and Clinical Immunology Unit, Fourth Internal Medicine Department, University of Athens Medical School, ‘‘Attikon’’ University Hospital, Athens, Greece
for polyarthritis and nodular erythema 10 years ago, but Rheumatologists had reached no conclusion at that stage despite the thorough investigation. Her symptoms had disappeared a few weeks later with no treatment. Her family history was unremarkable. Endoscopy revealed a diffusely swollen epiglottis, false vocal folds, and arytenoids (Fig. 1). There were no palpable neck masses and the rest of ENT examination was normal. CT scan confirmed the epiglottal edema with no nodal involvement. Her laboratory tests included total blood count, biochemistry, and immunology testing that were all normal with the exception of anti-nuclear antibody that was slightly above normal levels. The patient underwent biopsy of the epiglottis under local anesthesia (Fig. 2).
What is the Diagnosis? Histology showed lymphoid tissue covered by stratified squamous epithelium and containing a few, disseminated, sarcoid-type granulomas (lacking necrosis or central suppuration), whereas special histochemical stains (PAS, Grocott) disclosed no fungi (Fig. 3). Real-time polymerase chain reaction (RT-PCR) of the tissue specimen was negative for DNA of M. tuberculosis. Further radiologic examination failed to confirm the presence of the disease in other organs. Laryngeal sarcoidosis was the diagnosis established. She was placed on oral prednisolone, starting with 60 mg a day for 3 weeks followed by 30 mg a day for 6 weeks. After initial partial improvement, her symptoms deteriorated and methotrexate was added starting from 5 mg, further reducing the dose. 6 months after, she is
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A. Delides et al.: Dysphagia Caused by Chronic Laryngeal Edema
Fig. 1 Fiberoptic laryngoscopy view of the thickened, edematous epiglottis
Fig. 3 Histology: a lymphoid tissue covered by stratified squamous epithelium (left) and containing a few, disseminated, sarcoid-type granulomas. Hematoxylin and eosin stain, 94. b Sarcoid-type granulomas (lacking necrosis or central suppuration) within lymphoid tissue. Hematoxylin and eosin stain, 920. c Epithelioid granulomas outlined with anti-CD68 (PGM-1) immunostain, 920 Fig. 2 Under fiberoptic laryngoscopy, a punch biopsy of the epiglottis is taken
completely free of symptoms, still receiving prednisolone 10 mg per day and oral methotrexate 2.5 mg.
Discussion Sarcoidosis is a chronic granulomatous disease that can affect any organ system but predominately the lungs, hilar and mediastinal lymph nodes, liver, eyes, skin, bones, and nervous system [1]. Head and neck involvement is rare and isolated laryngeal involvement is even more exceptional. The disease is characterized by tissue infiltration by mononuclear phagocytes and lymphocytes with associated non-caseating granuloma formation. In spite of the advances in etiology of sarcoidosis, which seems to involve the human leukocyte antigen genes, its etiology remains
123
undetermined. It was initially described in 1869 by Hutchinson and it usually affects young adults [1]. The signs and symptoms of sarcoidosis in the area of head and neck are not specific and can mimic much more common disorders. Biopsy is usually necessary to make the diagnosis [2], but sometimes can be non-diagnostic and needs to be repeated. Laryngeal sarcoidosis is rare and counts for approximately 0.5–0.9 % of patients with sarcoidosis [3]. Even more rare is the incidence of isolated laryngeal sarcoidosis with, to the best of our knowledge, 58 possible cases described in the literature, although it is not clear for many of them if they represent solely laryngeal isolated cases. For almost all the above cases diagnosis was confirmed with biopsy from the affected area. Angiotensin-converting enzyme (ACE) sensitivity and specificity for sarcoidosis is not perfect [4]. In our case, ACE testing was negative as it may be in 40 % of patients depending on the granuloma load.
A. Delides et al.: Dysphagia Caused by Chronic Laryngeal Edema
The mainstay of treatment is steroids (mainly oral, inhaled, intra-lesional). In some of the published cases, surgical excision of edematous areas [3, 5] was undertaken, while isolated cases were managed with azathioprine [6], clofazimine [7], and radiotherapy [8] when steroid treatment proved to be ineffective. In one case, the disease improved without specific treatment [9]. In our case, steroid treatment was ineffective especially when an attempt was made to taper the dosage and methotrexate was added. Duration of treatment depends on symptoms. Sarcoidosis should be suspected in every diffuse, infection resembling, edema of the larynx, especially if there is an immunology-related past medical history despite the absence of lower respiratory system symptoms and negative ACE. The absence of pain and fever is characteristic in order to differentiate from epiglottitis and the disease might remain undiagnosed for long unless a biopsy is taken. A punch biopsy, as in our case under local anesthesia, provides adequate specimen to establish the diagnosis. Swallowing difficulty and globus sensation might be the only symptom.
585
References 1. Spagnolo P. Sarcoidosis: a critical review of history and milestones. Clin Rev Allergy Immunol. 2015. doi:10.1007/ s12016-015-8480-0. 2. Schwartzbauer HR, Tami TA. Ear, nose, and throat manifestations of sarcoidosis. Otolaryngol Clin N Am. 2003;36:673–84. 3. Plaschke CC, Owen HH, Rasmussen N. Clinically isolated laryngeal sarcoidosis. Eur Arch Otorhinolaryngol. 2011;268: 575–80. 4. Baudin B. Angiotensin I-converting enzyme (ACE) for sarcoidosis diagnosis. Pathol Biol (Paris). 2005;53:183–8. 5. Kenny TJ, Werkhaven J, Netterville JL. Sarcoidosis of the pediatric larynx. Arch Otolaryngol Head Neck Surg. 2000;126:536–9. 6. Agrawal Y, Godin DA, Belafsky PC. Cytotoxic agents in the treatment of laryngeal sarcoidosis: a case report and review of the literature. J Voice. 2006;20:481–4. 7. Sakamoto M, Ishizawa M, Kitahara N. Polypoid type of laryngeal sarcoidosis—case report and review of the literature. Eur Arch Otorhinolaryngol. 2000;257:436–8. 8. Fogel TD, Weissberg JB, Dobular K, Kirchner JA. Radiotherapy in sarcoidosis of the larynx: case report and review of the literature. Laryngoscope. 1984;94:1223–5. 9. Genard F, Desuter G, Weynand B, Lambert M. Laryngeal sarcoidosis: case report. Rev Laryngol Otol Rhinol (Bord). 2009;130:133–6.
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CLINICAL CONUNDRUM
Dysphagia Caused by Chronic Laryngeal Edema Alexander Delides1 • George Sakagiannis1 • Pavlos Maragoudakis1 • Alina-Roxani Gouloumi2 • Pelagia Katsimbri3 • Ioannis Giotakis1 • John G. Panayiotides2
Received: 15 May 2015 / Accepted: 30 June 2015 / Published online: 7 July 2015 Ó Springer Science+Business Media New York 2015
Abstract A rare case of a young female with chronic diffuse laryngeal edema causing severe swallowing difficulty is presented. The patient was previously treated with antibiotics and steroids with no improvement. Diagnosis was made with biopsy of the epiglottis under local anesthesia in the office. Keywords Deglutition Deglutition disorders Laryngeal edema Laryngeal diseases Sarcoidosis
Case Presentation A 39-year-old female living in a small isolated Greek island was admitted in our Department with a 4-month history of intermittent dyspnea, globus sensation, and severe swallowing difficulty affecting predominately solids. She was afebrile and did not complain for pain during swallowing. She had been visiting her family physician and was prescribed with antibiotics and oral steroids with no improvement. Her past medical history included tonsillectomy 8 years ago for recurrent tonsil infection. She was also investigated
& Alexander Delides [email protected] 1
2nd Otolaryngology Department, University of Athens Medical School, ‘‘Attikon’’ University Hospital, 1 Rimini St., Chaidari, 124 62 Athens, Greece
2
2nd Department of Pathology, University of Athens Medical School, ‘‘Attikon’’ University Hospital, Athens, Greece
3
Rheumatology and Clinical Immunology Unit, Fourth Internal Medicine Department, University of Athens Medical School, ‘‘Attikon’’ University Hospital, Athens, Greece
for polyarthritis and nodular erythema 10 years ago, but Rheumatologists had reached no conclusion at that stage despite the thorough investigation. Her symptoms had disappeared a few weeks later with no treatment. Her family history was unremarkable. Endoscopy revealed a diffusely swollen epiglottis, false vocal folds, and arytenoids (Fig. 1). There were no palpable neck masses and the rest of ENT examination was normal. CT scan confirmed the epiglottal edema with no nodal involvement. Her laboratory tests included total blood count, biochemistry, and immunology testing that were all normal with the exception of anti-nuclear antibody that was slightly above normal levels. The patient underwent biopsy of the epiglottis under local anesthesia (Fig. 2).
What is the Diagnosis? Histology showed lymphoid tissue covered by stratified squamous epithelium and containing a few, disseminated, sarcoid-type granulomas (lacking necrosis or central suppuration), whereas special histochemical stains (PAS, Grocott) disclosed no fungi (Fig. 3). Real-time polymerase chain reaction (RT-PCR) of the tissue specimen was negative for DNA of M. tuberculosis. Further radiologic examination failed to confirm the presence of the disease in other organs. Laryngeal sarcoidosis was the diagnosis established. She was placed on oral prednisolone, starting with 60 mg a day for 3 weeks followed by 30 mg a day for 6 weeks. After initial partial improvement, her symptoms deteriorated and methotrexate was added starting from 5 mg, further reducing the dose. 6 months after, she is
123
584
A. Delides et al.: Dysphagia Caused by Chronic Laryngeal Edema
Fig. 1 Fiberoptic laryngoscopy view of the thickened, edematous epiglottis
Fig. 3 Histology: a lymphoid tissue covered by stratified squamous epithelium (left) and containing a few, disseminated, sarcoid-type granulomas. Hematoxylin and eosin stain, 94. b Sarcoid-type granulomas (lacking necrosis or central suppuration) within lymphoid tissue. Hematoxylin and eosin stain, 920. c Epithelioid granulomas outlined with anti-CD68 (PGM-1) immunostain, 920 Fig. 2 Under fiberoptic laryngoscopy, a punch biopsy of the epiglottis is taken
completely free of symptoms, still receiving prednisolone 10 mg per day and oral methotrexate 2.5 mg.
Discussion Sarcoidosis is a chronic granulomatous disease that can affect any organ system but predominately the lungs, hilar and mediastinal lymph nodes, liver, eyes, skin, bones, and nervous system [1]. Head and neck involvement is rare and isolated laryngeal involvement is even more exceptional. The disease is characterized by tissue infiltration by mononuclear phagocytes and lymphocytes with associated non-caseating granuloma formation. In spite of the advances in etiology of sarcoidosis, which seems to involve the human leukocyte antigen genes, its etiology remains
123
undetermined. It was initially described in 1869 by Hutchinson and it usually affects young adults [1]. The signs and symptoms of sarcoidosis in the area of head and neck are not specific and can mimic much more common disorders. Biopsy is usually necessary to make the diagnosis [2], but sometimes can be non-diagnostic and needs to be repeated. Laryngeal sarcoidosis is rare and counts for approximately 0.5–0.9 % of patients with sarcoidosis [3]. Even more rare is the incidence of isolated laryngeal sarcoidosis with, to the best of our knowledge, 58 possible cases described in the literature, although it is not clear for many of them if they represent solely laryngeal isolated cases. For almost all the above cases diagnosis was confirmed with biopsy from the affected area. Angiotensin-converting enzyme (ACE) sensitivity and specificity for sarcoidosis is not perfect [4]. In our case, ACE testing was negative as it may be in 40 % of patients depending on the granuloma load.
A. Delides et al.: Dysphagia Caused by Chronic Laryngeal Edema
The mainstay of treatment is steroids (mainly oral, inhaled, intra-lesional). In some of the published cases, surgical excision of edematous areas [3, 5] was undertaken, while isolated cases were managed with azathioprine [6], clofazimine [7], and radiotherapy [8] when steroid treatment proved to be ineffective. In one case, the disease improved without specific treatment [9]. In our case, steroid treatment was ineffective especially when an attempt was made to taper the dosage and methotrexate was added. Duration of treatment depends on symptoms. Sarcoidosis should be suspected in every diffuse, infection resembling, edema of the larynx, especially if there is an immunology-related past medical history despite the absence of lower respiratory system symptoms and negative ACE. The absence of pain and fever is characteristic in order to differentiate from epiglottitis and the disease might remain undiagnosed for long unless a biopsy is taken. A punch biopsy, as in our case under local anesthesia, provides adequate specimen to establish the diagnosis. Swallowing difficulty and globus sensation might be the only symptom.
585
References 1. Spagnolo P. Sarcoidosis: a critical review of history and milestones. Clin Rev Allergy Immunol. 2015. doi:10.1007/ s12016-015-8480-0. 2. Schwartzbauer HR, Tami TA. Ear, nose, and throat manifestations of sarcoidosis. Otolaryngol Clin N Am. 2003;36:673–84. 3. Plaschke CC, Owen HH, Rasmussen N. Clinically isolated laryngeal sarcoidosis. Eur Arch Otorhinolaryngol. 2011;268: 575–80. 4. Baudin B. Angiotensin I-converting enzyme (ACE) for sarcoidosis diagnosis. Pathol Biol (Paris). 2005;53:183–8. 5. Kenny TJ, Werkhaven J, Netterville JL. Sarcoidosis of the pediatric larynx. Arch Otolaryngol Head Neck Surg. 2000;126:536–9. 6. Agrawal Y, Godin DA, Belafsky PC. Cytotoxic agents in the treatment of laryngeal sarcoidosis: a case report and review of the literature. J Voice. 2006;20:481–4. 7. Sakamoto M, Ishizawa M, Kitahara N. Polypoid type of laryngeal sarcoidosis—case report and review of the literature. Eur Arch Otorhinolaryngol. 2000;257:436–8. 8. Fogel TD, Weissberg JB, Dobular K, Kirchner JA. Radiotherapy in sarcoidosis of the larynx: case report and review of the literature. Laryngoscope. 1984;94:1223–5. 9. Genard F, Desuter G, Weynand B, Lambert M. Laryngeal sarcoidosis: case report. Rev Laryngol Otol Rhinol (Bord). 2009;130:133–6.
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