Lichenoid Dermatitis in Paraneoplastic Pemphigus

Bowen, Glen M.; Peters, Neill T.; Fivenson, David P.; Su, Lyndon D.; Nousari, Hossein C.; Anhalt, Grant J.; Cooper, Kevin D.; Stevens, Seth R.

doi:10.1001/archderm.136.5.652

Cited by 85 publications

(24 citation statements)

References 33 publications

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“…However, despite their ubiquitous expression, their role in disease initiation is unlikely, since they are cytoplasmic proteins [8], [11]. Furthermore, though the majority of PNP sera also immunoprecipitate the p170 autoantigen, the search for the identity of this protein has proved to be technically challenging [9], [12], [13]. Finally, CD8+ cytotoxic T lymphocytes and other mononuclear cells are likely to contribute to tissue damage resulting in keratinocyte necrosis and apoptosis with a graft-versus-host disease-like phenotype in the skin [6], [14].…”

Section: Introductionmentioning

confidence: 99%

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

et al. 2010

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BackgroundParaneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown.Methodology/Principal FindingsUsing an immunoprecipitation and mass spectrometry based approach, we identified p170 as alpha-2-macroglobuline-like-1, a broad range protease inhibitor expressed in stratified epithelia and other tissues damaged in the PNP disease course. We demonstrate that 10 PNP sera recognize alpha-2-macroglobuline-like-1 (A2ML1), while none of the control sera obtained from patients with bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus and normal subjects does.Conclusions/SignificanceOur study unravels a broad range protease inhibitor as a new class of target antigens in a paraneoplastic autoimmune multiorgan syndrome and opens a new challenging investigation avenue for a better understanding of PNP pathogenesis.

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Section: Introductionmentioning

confidence: 99%

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

et al. 2010

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“…Other authors have postulated that paraneoplastic skin eruptions promote exposure of self-antigens and subsequent development of auto-antibodies. 15 Epitope spreading may then occur, where tissue damage exposes additional self-antigens, thereby diversifying the auto-antibodies to recognize additional proteins. 16 Criteria for diagnosis were devised by Anhalt and colleagues in their original article.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, response to treatment is generally poor, and PNP frequently results in premature death compared to the average life expectancy associated with the underlying malignancy. 3,15 The prognosis is generally more favorable in patients with benign neoplasms, such as Castleman's syndrome or thymoma 3 . In summary, paraneoplastic pemphigus is a rare, polymorphous blistering disease with a predilection for the mucosal surfaces in the setting of an associated neoplasm.…”

Section: Discussionmentioning

confidence: 99%

Paraneoplastic Pemphigus in a Patient with Carcinosarcoma of the Uterus

Giebel¹,

Shah²

2010

TMF

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The patient is a 68-year-old female with hypertension, chronic obstructive pulmonary disease, without medical follow-up for several years, who initially presented with skin blisters and oral lesions, which were biopsied by her dermatologist and found to be bullous pemphigoid. She was treated with a course of oral prednisone and had resolution of her skin and oral lesions. Three months later, she presented with a swollen leg and was diagnosed with a deep venous thrombosis, for which she was started on coumadin and had an inferior vena cava filter placed. She then had hemoptysis a few days later, after which the coumadin was held. A chest computed tomography (CT) done at that time found a right middle lobe consolidation consistent with aspiration pneumonia and a cavitary lesion in the left upper lobe of her lung, which was biopsied and found to be a necrotizing cavitary lung lesion. After being ruled out for tuberculosis, she had an outpatient positron emission tomography (PET) scan which was positive for a 2.7cm left lower lobe cavitary lesion and a 9 cm pelvic mass with hypermetabolic activity, as well as small liver lesions. Concurrently, she complained of dysphagia and 30-lbs of weight loss over the prior six months, so the decision was made to undergo an outpatient esophagogastroduodenoscopy (EGD). The EGD could not be completed secondary to a stricture in the distal esophagus; however, pemphigus ulcers were seen in the mouth and esophagus. Given the patient's degree of malnourishment and dehydration, she was admitted to the outside hospital. On admission, she was found to have leukocytosis with a white blood cell count of 37,000/L, hypercalcemia with a calcium of 13mg/dL, hypotension, and acute renal failure with a creatinine of 4.4mg/dL. Her parathyroid hormone-related protein (PTHrP) was 105 pmol/L (normal <1.3 pmol/L), while her intact parathyroid hormone (PTH) was <3pg/mL (10-55 pg/ml). A serum protein electrophoresis with immunoelectrophoreis was positive for an IgG lambda paraprotein. On bone marrow biopsy, there were 25% plasma cells consistent with multiple myeloma, though this diagnosis was questioned after transfer. For treatment of her hypercalcemia, she was given intravenous fluids and calcitonin with minimal improvement, but with resolution of her renal failure.The esophageal biopsy showed squamous mucosa with necrotic ulcer and chronic inflammation with fibrinous exudate. The pelvic mass was also biopsied which was consistent with carcinosarcoma with massive necrosis. The pathology revealed myxoid high-grade spindle cell sarcoma with pleomorphosis and extensive mitosis and poorly differentiated adenocarcinoma with papillary serous differentiation, as well as some smooth muscle differentiation. During her hospitalization, the skin blisters reappeared and were biopsied. The biopsy was consistent with paraneoplastic pemphigus. She was treated with three days of intravenous immunoglobulin (IVIg). She had an open jejunostomy tube placed for nutrition. At this point, she was transferred to Thomas Jef...

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“…Presumably the antibodies are induced as an antitumor response and then cross- react with the protein expressed in normal cells. Bowen et al [13]proposed that lichen planus may induce paraneoplastic pemphigus by epitope spreading, i.e. by demasking of the aforementioned desmosomal antigens.…”

Section: Discussionmentioning

confidence: 99%

Progressive Respiratory Failure in Paraneoplastic Pemphigus Associated with Chronic Lymphocytic Leukemia

Brönnimann¹,

Felbert²,

Streit³

et al. 2004

Dermatology

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A 70-year-old Caucasian man with chronic lymphocytic leukemia suffered from widespread, histologically proven cutaneous lichen planus responding to topical corticosteroids. 2 years later, he presented with painful erosive stomatitis and increasing dyspnea. Histology, direct and indirect immunofluorescence were diagnostic for paraneoplastic pemphigus. A full diagnostic workup could not disclose the cause of the progressive respiratory insufficiency. Despite aggressive treatment of the lymphocytic leukemia and the paraneoplastic pemphigus, the patient died 3 months after diagnosis. Paraneoplastic pemphigus may lead to pulmonary failure which is refractory to treatment and has a fatal outcome.

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Lichenoid Dermatitis in Paraneoplastic Pemphigus

Cited by 85 publications

References 33 publications

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

Paraneoplastic Pemphigus in a Patient with Carcinosarcoma of the Uterus

Progressive Respiratory Failure in Paraneoplastic Pemphigus Associated with Chronic Lymphocytic Leukemia

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