Bay Biosciences provides high-quality, fresh frozen biopsy tissue samples. Formalin fixed paraffin embedded (FFPE) tissue blocks with matched fresh frozen sera (serum), plasma, and peripheral blood mononuclear cells (PBMC) bio-fluids, from patients diagnosed with paraneoplastic pemphigus (PNP).
The sera (serum), plasma and PBMC biofluid specimens are processed from patient’s peripheral whole-blood using customized collection and processing protocols from paraneoplastic pemphigus (PNP) patients.
Fresh frozen tissue and matched biofluid samples are collected from unique patients diagnosed with paraneoplastic pemphigus (PNP).
Bio-samples are provided to a valued pharmaceutical customer for research, diagnostics, discovery and drug development.
Pemphigus
Pemphigus is a group of skin disorders that cause blisters or pus-filled bumps. Lesions usually develop on the skin, but they can also form in the mucous membranes (soft linings of the eyes, nose, mouth, throat, and genitals).
The blisters are soft and break open easily to form painful sores. Without treatment, they can spread over large areas of the body and have a high risk of infection.
Pemphigus is an autoimmune disorder that can occur in otherwise healthy people. It is sometimes confused with other autoimmune blistering skin diseases such as bullous pemphigoid, systemic lupus erythematosus (SLE), and Hailey-Hailey disease.
Pemphigus is not contagious. It is a lifelong condition that can be managed with ongoing medical treatment.
Types of Pemphigus
Pemphigus is classified into different types based on the location where and the reason why blisters develop. In most cases, patients only get one type of pemphigus.
Types of pemphigus include:
- Pemphigus Vulgaris (PV): This type of pemphigus is the most common in the United States. Blisters essentially always affect the mouth. Some affected patients may also form blisters on the skin and in other mucous membranes. These lesions develop in deep layers of the skin. They can be painful and slow to heal.
- Pemphigus Vegetans: This type of pemphigus is related to pemphigus vulgaris. It involves lesions that are thicker and wart-like. These lesions usually form in the areas of the body with skin folds such as the groin area and armpits.
- Drug-induced Pemphigus: Medications cause blistering with this type of pemphigus. Some drugs that may cause this condition include penicillin and piroxicam. Blisters can develop up to six months after taking the offending drugs.
- Pemphigus Erythematosus: : This type of pemphigus also known as as Senear-Usher syndrome, involves blisters that develop on the upper back, chest, cheeks, and scalp. When lesions form, they are usually red and crusty.
- Pemphigus Foliaceus (PF) : In PF, blisters develop on the scalp and often the face, neck, and back. Lesions rarely appear in the mouth with pemphigus foliaceus. This type of pemphigus affects the outermost skin layer only. Small blisters may break easily to form crusted lesions that spread to cover large areas of skin.
- Endemic pemphigus (fogo selvagem): Endemic pemphigus is a form of pemphigus foliaceus that occurs more often in South and Central America, particularly Brazil. This form of the disease often affects multiple family members.
- Paraneoplastic pemphigus: This rarest type of pemphigus develops in patients with cancer. Blisters in the mouth that resist treatment may be the first sign. If your doctors diagnose paraneoplastic pemphigus, they will look for signs of a tumor somewhere in your body. Removing the tumor often improves the symptoms of paraneoplastic pemphigus.
Paraneoplastic Pemphigus (PNP) Overview
Paraneoplastic pemphigus (PNP) is a fatal rare autoimmune blistering disease associated with an underlying malignancy. PNP most frequently occurs in patients between 45 and 70 years old, but it also occurs in children and adolescents.
PNP mostly develops in cancer patients and in association with other malignancies. Usually it is triggered by neoplasias, mainly of lymphoproliferative origin such as chronic lymphocytic leukemia, multiple myeloma (MM), non-Hodgkin’s lymphoma, Castleman disease, and thymoma.
This disorder is characterized by the presence of autoantibodies that react against proteins, such as desmoplakins, desmocollins, and others existing in cell junctions.
The prognosis is reserved, and the mortality rate of the disease is very high, thus proving to be an additional challenge in the therapeutic management of onco-hematological diseases. Since it is a systemic disease that can affect the kidneys, bladder, and smooth and striated muscles.
PNP is a disease triggered mainly by B-cell lymphomas and malignant hematological diseases. Other neoplasms also demonstrate the onset of this disease, as well as carcinoma of the stomach, lung, and colon.
The patients with PNP present high mortality rates, being around 90% of the cases, besides presenting an extremely complex and difficult diagnosis, since it resembles several other diseases.
The treatment and management of this disease are often ineffective, as it is an extremely aggressive and lethal disease.
PNP representing 3–5% of all cases of pemphigus in the population. The vast majority of affected patients demonstrate lymphoproliferative disorders (LPD).
A wide variety of lesions (florid oral mucosal lesions, a generalized polymorphous cutaneous eruption, and pulmonary involvement) may occur in patients with PNP.
Many paraneoplastic pemphigus (PNP) patients have devastating bronchiolitis obliterans as a manifestation of their disease. In this condition bronchioles can become injured as a result of inhaling a harmful substance or due to an infection.
The thick scar tissue blocks the bronchioles and prevents air from passing through to the alveoli, or air sacs. This impairs the body’s ability to absorb oxygen. The scarring and narrowing of the bronchioles may continue to worsen over time, eventually resulting in respiratory failure.
Triggers of paraneoplastic pemphigus (PNP)
PNP can be triggered by several types of neoplasias, some of which are the following:
- Non-Hodgkin’s lymphoma
- Castleman disease
- Chronic lymphocytic leukemia
Sarcomas
- Leiomyosarcoma
- Malignant nerve sheath tumor
- Poorly differentiated sarcoma
- Reticular cell sarcoma
- Dendritic cell sarcoma
- Liposarcoma
- Inflammatory myofibroblastoma
Other less common diseases include the following:
- Colon carcinoma
- Lymphoepithelioma-like carcinoma
- Malignant thymoma
- Squamous cell carcinoma of the esophagus
- Retroperitoneal Kaposi’s sarcoma
- T-cell lymphoma
Although the PNP is triggered by several neoplasias, the manifestations of this disease may precede the hematological disorders and other malignancies, thus requiring the frequent and continuous follow-up of these patients.
Clinical Features of Paraneoplastic Pemphigus (PNP)
PNP presents several symptoms and clinical evolutions. The first symptoms as well as the progression of the disease are very varied from one patient to another. Following are some of the symptoms of PNP:
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Oral Lesions: The oral mucosa is often affected in patients with PNP. Oral symptoms may be the first symptoms in these patients, even before skin lesions. The most common symptoms are oral and labial erosions with bleeding that may be associated with blisters, macules, papules, vesicles, and erythema.
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Secondary Mucosal Lesions: Lesions can also affect regions such as the oropharynx, esophagus, stomach, duodenum, large intestine, conjunctiva, and anogenital region. The involvement of the oropharynx and esophagus commonly triggers painful sensations and dysphagia.
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Skin Lesions: Skin lesions usually appear on the dorsal region head, and neck, in addition to the nearby extremities.
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Pulmonary Manifestations: Over 90% of PNP cases have pulmonary involvement, it is the main cause of death in patients with PNP. The pulmonary clinical signs of PNP are dyspnea, obstructive pulmonary disease, and bronchiolitis obliterans.
Diagnosis of Paraneoplastic Pemphigus (PNP)
Diagnosis of paraneoplastic pemphigus (PNP) are based on the following five criteria:
- Clinical characteristics: Clinical features of severe and protracted mucosal involvement and polymorphic cutaneous eruptions.
- Histopathological analysis: Histologic features of acantholysis or lichenoid or interface dermatitis.
- Direct and indirect immunofluorescence: Demonstration of antiplakin autoantibodies.
- Immunoprecipitation: The presence of an underlying neoplasm, especially lymphoproliferative tumors.
Treatment of Paraneoplastic Pemphigus (PNP)
Effective treatment for PNP is still a major puzzle because of its rarity. Although several drugs are used in the literature, PNP has shown great resistance when compared to other forms of pemphigus.
Currently, the first-line treatment for PNP is still high doses of corticosteroids. This treatment improves the cutaneous lesions, but the mucosal involvement is little altered. The use of other drugs also shows little efficacy in the lesions of the mucosa, this resistance being the characteristic of the disease.
Several studies have shown that the combination of drugs has been effective and safe. These associations were prednisolone used with other therapies, such as mycophenolate mofetil, cyclosporine A, azathioprine, plasmapheresis, and intravenous immunoglobulin.
Even though treatment is more effective, mucosal involvement is still resistant to such combined therapies.
The use of monoclonal antibody has been effective in the treatment of PNP in some cases. Administration of rituximab, an anti-CD20, has shown good PNP therapy due to B-cell lymphoma.
This therapy is based on an infusion of 375 mg weekly for 4 weeks followed by eight weekly infusions for 4 weeks of corticosteroid and administration of other immunosuppressive drugs such as cyclosporine A.
Although there are several treatment alternatives, new therapies that reduce the resistance of PNP to drugs are still fundamental. Daclizumab, a monoclonal antibody against T-cell interleukin-2, has been shown to be a promising therapy.
In addition, the use of intravenous immunoglobulin before and during operations has demonstrated a significant reduction in mortality caused by bronchiolitis obliterans. Even after complete tumor resolution, immunoglobulin administration is required until 2 years to provide remission of autoimmunity triggered by PNP.
there are still no known drugs that reduce the mortality of patients, since the PNP proves highly resistant to more aggressive therapies. However, it is known that management, diagnosis, and early treatment are indispensable methods for a better response of the patients in the prescribed procedures.
Prognosis of Paraneoplastic Pemphigus (PNP)
The prognosis of PNP is extremely poor. Mortality can reach 90% of the cases in the first year, 41% of mortality in the second year, and 38% of death in the third year with the disease.
Commonly, death is triggered by systemic complications such as bronchiolitis obliterans, sepsis, and bleeding in the gastrointestinal tract.
It is known that regardless of the cure or control of the neoplasia, the PNP progresses, demonstrating itself autonomous to the triggering factor.
Patients who exhibit morbilliform erythema and necrosis of skin biopsy keratinocytes demonstrate a worse overall survival.
In some cases, the removal of Castleman disease and benign thymoma has shown better results than other underlying diseases.
Even with a high mortality rate, the prognosis depends very much on the proper management of the patient, such as monitoring of vital signs, control of oral and skin lesions, treatment of the triggering disease, and prevention of sepsis and bronchitis obliterans.
For this, it is essential to follow the patient closely and treat the disease aggressively.
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