JEADV
LETTER TO THE EDITOR
Pemphigus vulgaris of the epiglottis successfully treated with rituximab Editor Pemphigus lesions on the oral mucosa are the first manifestation of pemphigus vulgaris in 75%–80% of the cases.1 The nasal, pharyngeal, laryngeal and oesophageal mucosae may also be affected. Pemphigus on the epiglottis is of unknown frequency, but of high severity, as obstruction of the upper airway can occur due to oedema.2 A 55-year-old woman with hoarseness, haemoptisis, and stuffiness presented to our outpatient clinic. Clinical examination of the oral cavity revealed no lesions, whereas laryngoscopy revealed extensive lesions on the laryngeal surface of the epiglottis (Fig. 1). There were no skin lesions. The patient reported a history of pemphigus vulgaris with occasional flares of oral ulcers, but no cutaneous involvement for the last 5 years. A new biopsy specimen from an epiglottis lesion showed mucosal tissues with acantholysis of the epidermis, suprabasal blister formation and inflammatory cellular infiltration in the dermis (Fig. 2). Direct immunofluorescence showed granular deposition of IgG in the intercellular space of keratinocytes of the epidermis. Indirect immunofluorescence (IIF) using monkey oesophagus substrate detected anticell surface antibodies at a titre of 1 : 160. Anti-Dsg3 antibody index was positive by enzyme-linked immunosorbent assay. The diagnosis of pemphigus vulgaris was confirmed based on these data.
Figure 1 Direct laryngoscopy revealed multiple erosions on the epiglottis.
JEADV 2014
Figure 2 Pathology revealed mucosal tissues with acantholysis of the epidermis, suprabasal blister formation and inflammatory cellular infiltration in the dermis (Haematoxylin and Eosin 955).
The patient had been treated with prednizolone for 1 year in the past, starting with a dose of 50 mg per day that was tapered off to 5 mg per day. However, corticosteroids had caused osteoporosis, proximal motor weakness and hyperlipidaemia. Treatment with azathioprine 100 mg per day for 3 months was discontinued due to aseptic meningitis, and cyclophosphamide 50 mg per day for 2 weeks was discontinued due to a drug eruption. We decided to administer rituximab monotherapy 375 mg/ m2 per week i.v. for 4 weeks because the refractory lesions on the epiglottis could result in life-threatening obstruction of the airway due to oedema and conventional therapy administered in the past was either ineffective or contraindicated. She received one additional dose 6 months later. Improvement of the lesions was observed 2 weeks after the first infusion. Complete healing of epiglottis lesions was observed using laryngoscopy, 2 weeks after the fourth infusion and the patient reported no more discomfort. Antibodies titre was decreased to 1 : 80 at 4 weeks and was undetectable after 8 weeks using IIF. There were no adverse events including no infections during the next 6 months. Remission still persists 1 year after the last infusion.
© 2014 European Academy of Dermatology and Venereology
Letter to the Editor
2
Laryngeal involvement in pemphigus is common.3–7 Highest prevalence reported in medical literature has been estimated to 85%.4 References of localization of pemphigus solely on the epiglottis are rare.2 Rituximab is a human-mouse chimeric monoclonal antibody that targets the B-cell antigen CD20, and has been used in the treatment of pemphigus vulgaris.8,9 In 95% of patients treated at least partial remission is achieved.10 Experience in treating laryngeal lesions has yet to be gained. Pemphigus presenting with solely laryngeal, including epiglottis, lesions can be a reason of diagnostic and therapeutic delay and could occasionally be complicated with oedema and obstruction of the upper airway. Patients with pemphigus should be evaluated for laryngeal involvement using ear, nose and throat (ENT) endoscopy. Experts suggest that information related to traumatic physiological mechanisms on ENT areas (mainly chewing, nose blowing, swallowing, phonation) must be offered to patients to avoid the appearance of new active PV lesions.4 Rituximab provided an excellent outcome in our patient who presented with pemphigus refractory to conventional agents with lesions solely in an area with scarce evidence based therapeutic data. We suggest that rituximab could be considered as an effective and well-tolerated treatment of pemphigus vulgaris of the epiglottis in cases where conventional therapy fails.
References 1 Avgerinou G, Papafragkaki DK, Nasiopoulou A et al. Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris. J Eur Acad Dermatol Venereol 2013; 27: 430–435. 2 Vasiliou A, Nikolopoulos TP, Manolopoulos L et al. Laryngeal pemphigus without skin manifestations and review of the literature. Eur Arch Otorhinolaryngol 2007; 264: 509–512. 3 Espa~ na A, Fernandez S, del Olmo J et al. Ear, nose and throat manifestations in pemphigus vulgaris. Br J Dermatol 2007; 156: 733–737. 4 Fernandez S, Espa~ na A, Navedo M et al. Study of oral, ear, nose and throat involvement in pemphigus vulgaris by endoscopic examination. Br J Dermatol 2012; 167: 1011–1016. 5 Robati RM, Rahmati-Roodsari M, Dabir-Moghaddam P et al. Mucosal manifestations of pemphigus vulgaris in ear, nose, and throat; before and after treatment. J Am Acad Dermatol 2012; 67: e249–e252. 6 Kavala M, Altıntasß S, Kocat€ urk E et al. Ear, nose and throat involvement in patients with pemphigus vulgaris: correlation with severity, phenotype and disease activity. J Eur Acad Dermatol Venereol 2011; 25: 1324–1327. 7 Su O, Onsun N, Meric Teker A et al. Upper airway tract and upper gastrointestinal tract involvement in patients with pemphigus vulgaris. Eur J Dermatol 2010; 20: 792–796. 8 Kanwar AJ, Tsuruta D, Vinay K et al. Efficacy and safety of rituximab treatment in Indian pemphigus patients. J Eur Acad Dermatol Venereol 2013; 27: e17–e23. 9 Cho HH, Jin SP, Chung JH. Clinical experiences of different dosing schedules of rituximab in pemphigus with various disease severities. J Eur Acad Dermatol Venereol 2013; 28: 186–191. 10 Schmidt E, Goebeler M, Zillikens D. Rituximab in severe pemphigus. Ann N Y Acad Sci 2009; 1173: 683–691. DOI: 10.1111/jdv.12536
S. Gregoriou,1,* X.-A. Koutsoukou,1 I. Panayotides,2 K. Theodoropoulos,1 P. Loumou,1 K. Prikas,3 A. Katoulis,1 D. Rigopoulos1 1 2nd Department of Dermatology and Venereology, 2Department of Pathology, 3Department of Head and Neck Surgery, Attikon Hospital, University of Athens Medical School, Athens, Greece *Correspondence: S. Gregoriou. E-mail: [email protected]
JEADV 2014
© 2014 European Academy of Dermatology and Venereology
LETTER TO THE EDITOR
Pemphigus vulgaris of the epiglottis successfully treated with rituximab Editor Pemphigus lesions on the oral mucosa are the first manifestation of pemphigus vulgaris in 75%–80% of the cases.1 The nasal, pharyngeal, laryngeal and oesophageal mucosae may also be affected. Pemphigus on the epiglottis is of unknown frequency, but of high severity, as obstruction of the upper airway can occur due to oedema.2 A 55-year-old woman with hoarseness, haemoptisis, and stuffiness presented to our outpatient clinic. Clinical examination of the oral cavity revealed no lesions, whereas laryngoscopy revealed extensive lesions on the laryngeal surface of the epiglottis (Fig. 1). There were no skin lesions. The patient reported a history of pemphigus vulgaris with occasional flares of oral ulcers, but no cutaneous involvement for the last 5 years. A new biopsy specimen from an epiglottis lesion showed mucosal tissues with acantholysis of the epidermis, suprabasal blister formation and inflammatory cellular infiltration in the dermis (Fig. 2). Direct immunofluorescence showed granular deposition of IgG in the intercellular space of keratinocytes of the epidermis. Indirect immunofluorescence (IIF) using monkey oesophagus substrate detected anticell surface antibodies at a titre of 1 : 160. Anti-Dsg3 antibody index was positive by enzyme-linked immunosorbent assay. The diagnosis of pemphigus vulgaris was confirmed based on these data.
Figure 1 Direct laryngoscopy revealed multiple erosions on the epiglottis.
JEADV 2014
Figure 2 Pathology revealed mucosal tissues with acantholysis of the epidermis, suprabasal blister formation and inflammatory cellular infiltration in the dermis (Haematoxylin and Eosin 955).
The patient had been treated with prednizolone for 1 year in the past, starting with a dose of 50 mg per day that was tapered off to 5 mg per day. However, corticosteroids had caused osteoporosis, proximal motor weakness and hyperlipidaemia. Treatment with azathioprine 100 mg per day for 3 months was discontinued due to aseptic meningitis, and cyclophosphamide 50 mg per day for 2 weeks was discontinued due to a drug eruption. We decided to administer rituximab monotherapy 375 mg/ m2 per week i.v. for 4 weeks because the refractory lesions on the epiglottis could result in life-threatening obstruction of the airway due to oedema and conventional therapy administered in the past was either ineffective or contraindicated. She received one additional dose 6 months later. Improvement of the lesions was observed 2 weeks after the first infusion. Complete healing of epiglottis lesions was observed using laryngoscopy, 2 weeks after the fourth infusion and the patient reported no more discomfort. Antibodies titre was decreased to 1 : 80 at 4 weeks and was undetectable after 8 weeks using IIF. There were no adverse events including no infections during the next 6 months. Remission still persists 1 year after the last infusion.
© 2014 European Academy of Dermatology and Venereology
Letter to the Editor
2
Laryngeal involvement in pemphigus is common.3–7 Highest prevalence reported in medical literature has been estimated to 85%.4 References of localization of pemphigus solely on the epiglottis are rare.2 Rituximab is a human-mouse chimeric monoclonal antibody that targets the B-cell antigen CD20, and has been used in the treatment of pemphigus vulgaris.8,9 In 95% of patients treated at least partial remission is achieved.10 Experience in treating laryngeal lesions has yet to be gained. Pemphigus presenting with solely laryngeal, including epiglottis, lesions can be a reason of diagnostic and therapeutic delay and could occasionally be complicated with oedema and obstruction of the upper airway. Patients with pemphigus should be evaluated for laryngeal involvement using ear, nose and throat (ENT) endoscopy. Experts suggest that information related to traumatic physiological mechanisms on ENT areas (mainly chewing, nose blowing, swallowing, phonation) must be offered to patients to avoid the appearance of new active PV lesions.4 Rituximab provided an excellent outcome in our patient who presented with pemphigus refractory to conventional agents with lesions solely in an area with scarce evidence based therapeutic data. We suggest that rituximab could be considered as an effective and well-tolerated treatment of pemphigus vulgaris of the epiglottis in cases where conventional therapy fails.
References 1 Avgerinou G, Papafragkaki DK, Nasiopoulou A et al. Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris. J Eur Acad Dermatol Venereol 2013; 27: 430–435. 2 Vasiliou A, Nikolopoulos TP, Manolopoulos L et al. Laryngeal pemphigus without skin manifestations and review of the literature. Eur Arch Otorhinolaryngol 2007; 264: 509–512. 3 Espa~ na A, Fernandez S, del Olmo J et al. Ear, nose and throat manifestations in pemphigus vulgaris. Br J Dermatol 2007; 156: 733–737. 4 Fernandez S, Espa~ na A, Navedo M et al. Study of oral, ear, nose and throat involvement in pemphigus vulgaris by endoscopic examination. Br J Dermatol 2012; 167: 1011–1016. 5 Robati RM, Rahmati-Roodsari M, Dabir-Moghaddam P et al. Mucosal manifestations of pemphigus vulgaris in ear, nose, and throat; before and after treatment. J Am Acad Dermatol 2012; 67: e249–e252. 6 Kavala M, Altıntasß S, Kocat€ urk E et al. Ear, nose and throat involvement in patients with pemphigus vulgaris: correlation with severity, phenotype and disease activity. J Eur Acad Dermatol Venereol 2011; 25: 1324–1327. 7 Su O, Onsun N, Meric Teker A et al. Upper airway tract and upper gastrointestinal tract involvement in patients with pemphigus vulgaris. Eur J Dermatol 2010; 20: 792–796. 8 Kanwar AJ, Tsuruta D, Vinay K et al. Efficacy and safety of rituximab treatment in Indian pemphigus patients. J Eur Acad Dermatol Venereol 2013; 27: e17–e23. 9 Cho HH, Jin SP, Chung JH. Clinical experiences of different dosing schedules of rituximab in pemphigus with various disease severities. J Eur Acad Dermatol Venereol 2013; 28: 186–191. 10 Schmidt E, Goebeler M, Zillikens D. Rituximab in severe pemphigus. Ann N Y Acad Sci 2009; 1173: 683–691. DOI: 10.1111/jdv.12536
S. Gregoriou,1,* X.-A. Koutsoukou,1 I. Panayotides,2 K. Theodoropoulos,1 P. Loumou,1 K. Prikas,3 A. Katoulis,1 D. Rigopoulos1 1 2nd Department of Dermatology and Venereology, 2Department of Pathology, 3Department of Head and Neck Surgery, Attikon Hospital, University of Athens Medical School, Athens, Greece *Correspondence: S. Gregoriou. E-mail: [email protected]
JEADV 2014
© 2014 European Academy of Dermatology and Venereology
