Molecular Basis for Global Incidence of Pemphigoid Diseases and Differences in Phenotypes
A. Razzaque Ahmed a,*, Merve Aksoy a, T. Bernard Kinane b
a Center for Blistering Diseases, Department of Dermatology, Tufts University School of Medicine, Boston, MA, USA
b Chief Pediatric Pulmonary Medicine, Mass General Hospital, Harvard Medical School, Boston, MA, USA
Abstract
This review of Pemphigoid of the Pulmonary System (POPS) is a comprehensive description of pulmonary involvement in patients with mucous membrane pemphigoid (MMP), which is an orphan autoimmune blistering disease. The objective of the review was to analyze clinical features of pulmonary involvement in MMP. This POPS review is a case series in which multiple search engines were utilized from inception to June 2022 for cases of MMP with biopsy and immunopathology proven tracheal and bronchial pemphigoid. Clinical profiles prior to pulmonary involvement, bronchoscopy findings, clinical course and therapy were recorded and cause of death was analyzed.
Patients with documented MMP who developed tracheal, bronchial and pulmonary involvement were included in the POPS review. Histology and immunopathology documentation were essential diagnostic criteria. Comparison groups were not possible. Patients were treated with immunosuppressive therapy. Some required surgical interventions. Six of the 11 patients attained complete or partial remission on or off therapy. Five pa-tients died from pulmonary complications.
The POPS review had six females and five males. The mean age at onset was 20 years (range 4–76), while 80% of the patients were under 40 years. All had severe widespread MMP involving three to five mucosal tissues. 100% had oral, 82% had ocular and cutaneous involvement. Pulmonary involvement occurred at 24 mo (range 2–372) after the onset of MMP. Bronchoscopy revealed acute inflammation during active disease and scarring of the trachea and bronchi in the later stages. Systemic infections occurred in 45%, while pulmonary infection occurred in 36%. Mortality due to respiratory failure, at the median age of 20 years (range 18–76), occurred in 45% of the patients, and was considered disease related.
In spite of the young age, while there are some similarities in the clinical profile and response to systemic therapy, there are definitive differences from other patients with MMP. Early diagnosis with appropriate man-agement could produce better clinical outcomes and prevent mortality in this orphan disease. Consequently, there is a critical need for early identification and diagnosis of POPS.
Introduction
Mucous membrane Pemphigoid (MMP) is an orphan autoimmune mucocutaneous blistering disease, which may be potentially fatal [1]. It is exceedingly rare. The reported incidence is one to two patients per million population per year [2]. It is predominantly a mucosal disease affecting the ocular, nasal, oral, oropharyngeal, pharyngeal, laryngeal, tracheal, upper third of the esophagus, genital, and anal canal mucosa and the skin [1–4]. The distribution reported was oral mucosa (80–90%), ocular mucosa (50%), the skin (20%), genitalia (15%), anal mucosae (10%), pharynx (<10%), larynx (<10%) and esophagus (<10%), described in several reviews, [5–10]. Neither of them mention lower airway or pulmonary involvement.
The disease presents as intact bullae, vesicles, or erosions. A distinctive feature of this orphan disease is that, as the blisters or ero-sions heal, they result in scarring, except in the oral cavity [1]. The sequelae of this scarring process are consequential and devastating [1]. Ocular involvement can cause visual impairment in 30% and lead to bilateral blindness in 20–25% [11]. Nasal scarring reduces airway access [12]. Laryngeal involvement causes laryngeal stenosis, sudden asphyxiation, and death [12]. Esophageal stenosis causes dysphagia and, when severe, may require gastric tube feeding. Esophageal rupture causes fatal mediastinitis [13]. Vaginal stenosis excludes sexual activity and Pap smears are no longer possible [14]. Anal stenosis results in constant fecal leakage and a lifelong need for adult diapers [15].
The objective of this review of POPS was to examine clinical features, diagnosis, treatment, consequences and sequelae of such involvement, and associated high mortality rate. In so doing, the clinical entity of “pulmonary pemphigoid” (PPg) or POPS was described. There are many distinguishing features of POPS. Therefore, it may be considered an important late subset of MMP.
See full article at: Pemphigoid of the Pulmonary System (POPS): A Review of a Less Recognized Feature