Paraneoplastic pemphigus (PNP) is an uncommon autoimmune blistering mucocutaneous illness that is nearly invariably linked to an undetected or diagnosed tumor. In 3–5% of cases, it is the most severe but least common form of pemphigus. PNP can affect toddlers as well, even though it often affects adults between the ages of 45 and 70 who have an equal preference for male and female sexes. Nearly all PNP instances have a malignant condition beneath them.

Causes:

Although the exact origin of PNP is unknown, it seems that an underlying malignancy, most frequently a lymphoproliferative tumor, triggers an immunological reaction. The primary autoantigenic target in PNP is desmosomes. Possible causes and their underlying mechanisms a generated autoreactive T-cell induced humoral and cell-mediated immunity, IgG1 autoantibodies against desmosome and hemidesmosome, and specific gene variants, or alleles, such as the HLA-Cw*14 allele and the HLA Class II DRB1*03 allele.

Clinical features:

Often the only presenting feature of PNP is extensive refractory painful mucous membrane blisters, and hemorrhagic crusting involving the mucous membrane of various organs including the oropharynx, conjunctiva, lips, and genitals to name a few. A pruritic diffuse polymorphic rash can be seen following mucous membrane involvement. Systemic affection includes muscle weakness, and internal organs can be affected as well, with signs and symptoms of hidden malignancy.

Diagnosis:

A combination of clinical and histological findings, immunological serology, direct and indirect immunofluorescence, and other methods are used to diagnose PNP while keeping in mind that a search for underlying malignancy is important.

Histology findings depend on the clinical phenotype, the findings vary from suprabasal acantholysis, and lichenoid interface changes with a dense mononuclear immune cell infiltrate in the dermo-epidermal junction.

Direct immunofluorescence reveals granular or linear IgG and C3 deposits along the basement membrane zone at the dermo-epidermal junction. While indirect immunofluorescence reveals circulating antibodies targeting the intercellular proteins of cells within stratified squamous or transitional epithelium are characteristic of PNP. To diagnose PNP, autoantibodies against the 190-kD band of periplakin and the 210-kD band of envoplakin can be found. This method is both specific and sensitive.

Management:

The treatment of PNP is difficult and requires a multidisciplinary approach. General measures for PNP include an identification of infection, dehydration, extensive wound care, and analgesic mouthwashes. The best course of treatment for PNP is debatable, and response to therapy varies. Possible courses of treatment include topical corticosteroids or topical calcineurin inhibitors, Systemic immunosuppression agents, IVIG, and plasmapheresis. It will be necessary to treat the underlying malignancy with appropriate chemotherapy, radiation, or immunotherapy, or by surgical excision. It may take 6-18 months to observe complete resolution of the lesions after benign neoplasm excision.

Complications:

The complications of PNP include secondary bacterial infection, dehydration, ocular complications (pseudomembranous conjunctivitis, and, progressive scarring), and lung complications (bronchiolitis obliterans, and respiratory failure).

Prevention:

Prevention is difficult because PNP is usually always linked to underlying disease, especially hematopoietic cancers like leukemia and lymphoma. For PNP patients, surgical removal of solid tumors combined with high-dose IVIG used both before and after surgery can reduce the incidence of bronchiolitis obliterans.

Outcome:

PNP has a fatality rate that can range from 70% to 90%. The prognosis appears to be poorer for PNP patients with the erythema multiforme-like subtype. Widespread infections, the advancement of cancer, or bronchiolitis obliterans are among the causes of death. The prognosis for PNP may be improved by treatment using a range of medications.

Written by:

Mohammed Alahmadi, Medical Student.

Revised by:

Maee Barakeh, Medical Student.

References:

DermNet

Dermatology by Bolognia

Medscape