Skip to main content

Paraneoplastic pemphigus

 Paraneoplastic pemphigus



Overview

Paraneoplastic pemphigus (PNP) is a rare, severe autoimmune blistering disease triggered by an underlying cancer, often a lymphoma, causing painful blisters and erosions on skin and mucous membranes (especially the mouth). It involves autoantibodies attacking proteins that hold skin cells together, leading to widespread tissue breakdown and potentially fatal complications like bronchiolitis obliterans (lung inflammation). Diagnosis requires clinical signs, biopsies, and specific autoantibody tests, with treatment focused on controlling the underlying tumor and immunosuppression, though prognosis remains poor. 

Symptoms

Mucosal (Mouth/Throat): The most prominent symptom, featuring severe, painful, persistent erosions, ulcers, and crusting, especially on the lips (vermilion border) and tongue. 

Skin: A mix of blisters, erosions, crusts, and red/purple, scaly patches (lichenoid eruptions) that can look like other skin conditions (e.g., lichen planus, bullous pemphigoid). 

Eyes: Conjunctivitis (inflammation) and corneal scarring can occur. 

Lungs: Bronchiolitis obliterans (severe lung damage) is a major complication, causing shortness of breath (dyspnea). 

Complications

Respiratory System: Bronchiolitis Obliterans (BO) is a hallmark, damaging small airways, leading to chronic cough, shortness of breath, and respiratory failure, a leading cause of death.

Skin & Mucosa: Painful, extensive erosions (mouth, eyes, genitals, skin) cause extreme fluid/protein loss, dehydration, malnutrition, and increase infection risk.

Infection & Sepsis: Loss of skin barrier function and immunosuppression make patients prone to severe infections (pneumonia, sepsis).

Eyes: Conjunctival/corneal erosions, inflammation, scarring, eyelid thickening, and potential blindness.

Gastrointestinal System: Severe oral/pharyngeal pain hinders eating; GI bleeding can occur. 

Risk Factors

Hematologic Malignancies (Most Common):

Non-Hodgkin Lymphoma (NHL)

Chronic Lymphocytic Leukemia (CLL)

Castleman Disease (especially in children/adolescents)

Waldenstrom's Macroglobulinemia

Non-Hematologic Neoplasms (Less Common):

Thymoma

Sarcomas

Carcinomas (e.g., breast, colon, lung, skin)

Age: Primarily affects adults 45-70 years old.

Genetics (Potential): Certain HLA alleles (like Drb1*03) may increase susceptibility in some populations. 

Causes

Lymphoproliferative Disorders: The most frequent culprits, including Non-Hodgkin Lymphoma (especially follicular lymphoma), CLL, and Waldenström's macroglobulinemia.

Castleman Disease: A rare disorder of lymph nodes, strongly linked, especially in children.

Thymoma: Tumors of the thymus gland, also common.

Other Cancers: Less commonly, carcinomas (e.g., lung, gastrointestinal), sarcomas, and melanomas. 

Diagnosis

Clinical Presentation:

Major: Painful, persistent mouth sores (stomatitis) and polymorphic skin lesions (blisters, erosions).

Major: An underlying, often hidden, internal cancer (neoplasm), typically a lymphoma.

Histopathology (Skin Biopsy):

Shows intraepidermal acantholysis (cells separating) and necrotic keratinocytes (dying skin cells).

Direct Immunofluorescence (DIF) (on skin biopsy):

Confirms intercellular IgG/C3 deposits in the epidermis (net-like pattern) and often basement membrane zone (BMZ) staining.

Indirect Immunofluorescence (IIF) (Blood Test):

Uses substrates like rat bladder (or monkey esophagus) to detect circulating autoantibodies against various epithelial proteins, crucial for differentiating from other pemphigus types.

Immunoblotting & ELISA (Blood Test - Gold Standard):

Detects specific autoantibodies to desmogleins (Dsg1, Dsg3), desmocollins (Dsc1, Dsc2, Dsc3), and especially plakin family proteins (envoplakin, periplakin, plectin), and A2ML1. 

Treatment

Treat the Underlying Malignancy (Most Crucial):

Surgery: Complete tumor removal is vital, especially for solid tumors, to stop autoantibody production.

Chemotherapy/Radiation: May be needed depending on the cancer type (e.g., lymphomas).

Immunosuppression:

Corticosteroids: High doses (e.g., 1.5 mg/kg/day) are first-line to reduce inflammation.

Rituximab: Effective, especially for lymphomas.

Other Agents: Azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide used with variable success.

Supportive Care (Symptom Management):

Wound Care: Gentle cleaning, hydrating dressings (petroleum jelly gauze), and emollients for blisters and sores.

Pain Control: Topical pain relievers.

IVIG (Intravenous Immunoglobulin): Can help before/after surgery to reduce lung damage risk.

Nutritional Support: Essential due to severe oral involvement.

Type of Doctor Department : A dermatologist and an oncologist/hematologist

Comments

Post a Comment

Popular posts from this blog

Charge Syndrome

Overview CHARGE syndrome is a recognizable genetic syndrome with known pattern of features. It is an extremely complex syndrome, involving extensive medical and physical difficulties that differ from child to child. CHARGE syndrome is correlated with genetic mutation to CHD7 and the prevalence of CHARGE syndrome is 1:10,000-1:15,000 live births. Babies with CHARGE syndrome are often born with life-threatening birth defects. They spend many months in the hospital and undergo many surgeries and other treatments. Swallowing and breathing problems make life difficult even when they come home. Most have hearing two little girls sitting on a carpet, one girl has a trach and is biting her finger.loss, vision loss, and balance problems that delay their development and communication. Despite these seemingly insurmountable obstacles, children with CHARGE syndrome often far surpass their medical, physical, educational, and social expectations. One of the hidden features of CHARGE syndrome is the ...
7 comments
Read more

HMSN Type I

 HMSN Type I Overview Hereditary motor and sensory neuropathy type 1 (HMSN I), also known as Charcot-Marie-Tooth disease type 1 (CMT1), is a group of inherited neurological disorders affecting the peripheral nerves. It is characterized by progressive muscle weakness and wasting, primarily in the feet and legs, as well as sensory loss. HMSN I is the most common form of HMSN and is typically caused by a duplication on chromosome 17p11.2-p12, including the PMP22 gene.  Symptoms Numbness and tingling: Often starting in the feet and potentially extending to the hands, these sensations can mimic poor circulation.  Reduced ability to feel pain and temperature: This can lead to unnoticed injuries and complications.  Motor Symptoms: Muscle weakness and wasting: Primarily affecting the distal muscles (those farthest from the body's core), such as the feet and hands.  Foot deformities: High arches (pes cavus) and hammer toes are frequently observed.  Gait abnormalit...
Post a Comment
Read more

Sjogren's syndrome

Sjogren's syndrome Overview Sjogren's (SHOW-grins) syndrome is a disorder of your immune system identified by its two most common symptoms — dry eyes and a dry mouth. The condition often accompanies other immune system disorders, such as rheumatoid arthritis and lupus. In Sjogren's syndrome, the mucous membranes and moisture-secreting glands of your eyes and mouth are usually affected first — resulting in decreased tears and saliva. Although you can develop Sjogren's syndrome at any age, most people are older than 40 at the time of diagnosis. The condition is much more common in women. Treatment focuses on relieving symptoms. Symptoms The two main symptoms of Sjogren's syndrome are: Dry eyes . Your eyes might burn, itch or feel gritty — as if there's sand in them. Dry mouth. Your mouth might feel like it's full of cotton, making it difficult to swallow or speak. Some people with Sjogren's syndrome also have one or more of the following: Joint pain, swel...
Post a Comment
Read more