Necrotizing Tracheobronchitis With Progressive Airflow Obstruction Associated With Paraneoplastic Pemphigus

Osmanski, James P.; Fraire, Armando E.; Schaefer, Oren P.

doi:10.1378/chest.112.6.1704

Cited by 28 publications

(12 citation statements)

References 16 publications

(7 reference statements)

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“…Conjunctival involvement may lead to cicatrization, visual impairment, and even corneal perforation 5,6 . Involvement of the respiratory tract results in bronchiolitis obliterans, obstructive respiratory failure, and is almost universally fatal 7,8 …”

Section: Discussionmentioning

confidence: 99%

Paraneoplastic pemphigus resembling linear IgA bullous dermatosis

Lee

Tao

et al. 2006

Int J Dermatology

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A 69-year-old Chinese man presented in 2001 with a blistering eruption over the upper and lower limbs associated with oral ulceration for 1 month. He had stage IIIA follicular small cell cleaved non-Hodgkin's lymphoma diagnosed 5 years previously, and had received several lines of palliative chemotherapy, including two courses of chlorambucil, six cycles of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), and two four-cycle courses of rituximab, with disease stabilization at the time of presentation. Examination revealed erythematous, annular plaques with raised, urticarial borders studded with tense bullae and vesicles over the thighs. Some lesions were arciform and annular, with vesicles arranged in a ring at the border (Fig. 1). There was involvement of the feet with desquamation at the tips of the toes (Fig. 2). Severe erosions with hemorrhagic crusts on the lips, tongue, and buccal mucosa were seen. Herpes simplex virus serology was negative. A biopsy specimen from a vesicle on the left thigh showed suprabasal acantholysis (Fig. 3), some apoptotic keratinocytes (Fig. 4), satellite cell necrosis in the epidermis, and a superficial perivascular infiltrate of lymphocytes and eosinophils. Direct immunofluorescence showed intercellular immunoglobulin G (IgG) and C3 within the epidermis and along the basement membrane zone. Indirect immunofluorescence on monkey esophagus was positive for anti-intercellular antibody at a titre of 1/160 and positive on rat bladder at a titre of 1/80. A presumptive diagnosis of paraneoplastic pemphigus was made. This was later confirmed by the presence of antibodies against envoplakin (210 kDa), periplakin (190 kDa), and desmoglein 1 on immunoprecipitation studies. He was started on prednisolone 60 mg/day (1 mg/kg/day), with complete resolution of skin lesions within 1 week, but persistence of oral ulcers. Cyclophosphamide was added at a low dose of 1 mg/kg/day as he had baseline leukopenia. Cyclosporine was later added to a maximum of 4 mg/kg/day with only mild improvement of the oral lesions. He declined rituximab therapy. He died 2 months later from fulminant pneumonia.

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Section: Discussionmentioning

confidence: 99%

Paraneoplastic pemphigus resembling linear IgA bullous dermatosis

Lee

Tao

et al. 2006

Int J Dermatology

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“…Possible causes of the respiratory failure include infection, toxic effects induced by chemotherapy, neoplasia, and autoantibody-mediated pulmonary injury. [7][8][9][10][11][12][13][14][15][16] Deposits of IgG in the bronchial epithelium, which have sometimes been observed, 17 suggest that autoantibody-mediated injury has a role in this process.…”

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confidence: 99%

The Mechanism of Respiratory Failure in Paraneoplastic Pemphigus

et al. 1999

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“…However, the lungs of patients with PNP frequently show squamous metaplasia at autopsy or in bronchial biopsy specimens, which is often accompanied by CD4 + and CD8 + T cell infiltration (Fig. 5A) (8,10,31). Squamous metaplasia develops in response to acute or chronic inflammation caused by smoking (32) or viral infection (33)(34)(35), and it shows striking similarities to the skin and mucosa not only in terms of morphology, but also gene expression (36).…”

Section: Squamous Metaplasia Is Frequently Found In the Lungs Of Patimentioning

confidence: 99%

Ectopic Expression of Epidermal Antigens Renders the Lung a Target Organ in Paraneoplastic Pemphigus

Hata

Nishimoto

Nagao

et al. 2013

The Journal of Immunology

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Paraneoplastic pemphigus (PNP) is an autoimmune disease of the skin and mucous membranes that can involve fatal lung complications. IgG autoantibodies target the cell adhesion molecules desmoglein (Dsg)3 and plakins, but the nature and targets of infiltrating T cells are poorly characterized. Moreover, the lung involvement in this skin Ag-specific autoimmune condition represents a paradox. To mimic autoimmunity in PNP, we grafted wild-type skin onto Dsg3−/− mice, which resulted in graft rejection and generation of anti-Dsg3 IgG and Dsg3-specific T cells. Transfer of splenocytes from these mice into Rag2−/− mice induced a combination of suprabasilar acantholysis and interface dermatitis, a histology unique to PNP. Furthermore, the recipient mice showed prominent bronchial inflammation of CD4+ and CD8+ T cells with high mortality. Intriguingly, ectopic Dsg3 expression was observed in the lungs of PNP mice, mirroring the observation that squamous metaplasia is often found in the lungs of PNP patients. Dsg3 and other epidermal Ags were ectopically expressed in the lungs after pulmonary injuries by naphthalene, which was sufficient for recruitment of Dsg3-specific CD4+ T cells. These findings demonstrate that squamous metaplasia after pulmonary epithelial injury may play a crucial role in redirecting the skin-specific autoimmune reaction to the lungs in PNP.

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Necrotizing Tracheobronchitis With Progressive Airflow Obstruction Associated With Paraneoplastic Pemphigus

Cited by 28 publications

References 16 publications

Paraneoplastic pemphigus resembling linear IgA bullous dermatosis

Paraneoplastic pemphigus resembling linear IgA bullous dermatosis

The Mechanism of Respiratory Failure in Paraneoplastic Pemphigus

Ectopic Expression of Epidermal Antigens Renders the Lung a Target Organ in Paraneoplastic Pemphigus

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