What are the other Names for this Condition? (Also known as/Synonyms)

• PNP (Paraneoplastic Pemphigus)

What is Paraneoplastic Pemphigus? (Definition/Background Information)

• Paraneoplastic Pemphigus (PNP) is an uncommon but severe form of pemphigus, a blistering skin disorder, which develops in the setting of a malignancy, mostly lymphoproliferative diseases, such as chronic lymphocytic leukemia, among others. The condition is mainly observed in middle-aged and older adults
• Pemphigus is a benign and chronic skin disorder commonly affecting mid-to-elderly adults. It is characterized by the formation of painful blisters on the surface of the skin and mucous membranes, and is caused by immune system dysregulation
• Since Paraneoplastic Pemphigus develops against a backdrop of various cancers, a wide ranging presentation of cutaneous signs and symptoms with mucus surface involvement is noted. These include fluid-filled blisters, lichen planus-like lesions, erythema multiforme-like lesions, and erosive lesions. In many cases, a diagnosis of cancer may be made after the appearance of the skin lesions characteristic of PNP
• The management of Paraneoplastic Pemphigus includes promptly treating the underlying benign/malignant neoplasm. The skin lesions may be treated using topical and oral corticosteroids. Nevertheless, the overall prognosis of the condition is extremely poor due to severe complications noted, which include lung insufficiency, sepsis, and multiorgan failure

Who gets Paraneoplastic Pemphigus? (Age and Sex Distribution)

• Paraneoplastic Pemphigus (PNP) may be observed in individuals of all age groups. However, they are most common in the age group 45-70 years
• Both males and females are affected, and no gender predilection is seen
• Worldwide, the condition may affect individuals of all racial and ethnic groups. However, PNP is a rare form of pemphigus

What are the Risk Factors for Paraneoplastic Pemphigus? (Predisposing Factors)

The primary risk factor for Paraneoplastic Pemphigus (PNP) is the presence of a benign or malignant tumor. However, an association of PNP with a benign tumor is normally uncommon.

Lymphoproliferative diseases: According to medical literature, nearly 84% of the individuals with PNP present hematological (blood-related) cancers. These include:

• Non-Hodgkin lymphoma (in 38.6% of the cases)
• Chronic lymphocytic leukemia (18.4%)
• Castleman disease (18.4%)
• Carcinoma of the thymus gland or thymoma (5.5%)
• Waldenström's macroglobulinemia

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Paraneoplastic Pemphigus? (Etiology)

The exact cause of development of Paraneoplastic Pemphigus (PNP) is not well-understood. Research experts inform that it may develop due to a combination of genetic and environmental factors.

• PNP is described as an autoimmune (blistering) disorder of skin in which an individual's immune system attacks their own skin components, due to the production of immunoglobulin antibodies. This results in the characteristic signs and symptoms of the disorder
• PNP is generally observed against a background of a malignant neoplasm; however, the cause-effect relationship between the two is not well understood. It is believed that abnormal immune reaction of the body to the tumor cells may assist in the development of this skin condition

Paraneoplastic Pemphigus is not a contagious skin condition. It cannot be transmitted from one individual to another through direct physical contact or sharing of materials.

What are the Signs and Symptoms of Paraneoplastic Pemphigus?

The signs and symptoms of Paraneoplastic Pemphigus may vary vastly from one individual to another. The presentations are dependent on the type of benign or malignant tumor the individual is associated with. The signs and symptoms may include:

• Presence of polymorphous (various forms of) skin lesions that include blisters, vesicles, bullae, plaques, and erosions. Based on the characteristics of the lesions, these are described as:
  • Erythema multiforme-like skin lesions
  • Graft versus host disease-like lichenoid dermatosis or like Stevens-Johnson syndrome
  • Lichen planus-like lesions
  • Pemphigoid-like red skin blisters (larger and more often intact than in Pemphigus)
  • Pemphigus-like skin blisters
• The initial signs noted are swollen lips and ulcers in the mouth
• These progress to severe and painful mouth sores that ulcerate and bleed. Slowly, the esophagus and nasal cavity develop mucosal lesions
• Skin and nail involvement is noted following oral mucosal surfaces being affected. The palms of the hands are generally affected
• Skin involvement may occur after a few days to weeks and months after mucosal involvement
• The entire body may present skin lesions (mainly the trunk, head and neck region, and upper arms and thighs), including the eyes and anogenital surfaces
• Any type of lesions may develop, and these may transform from one type to another depending on the severity of the condition

How is Paraneoplastic Pemphigus Diagnosed?

It is reported that in about 33% of the cases, a diagnosis of the underlying neoplasm (benign/malignant tumor) is made following occurrence of the skin lesions. Hence, if a diagnosis of Paraneoplastic Pemphigus is suspected, it is important to undertake comprehensive investigations and scanning procedures to detect the associated tumor.

A diagnosis of Paraneoplastic Pemphigus may involve the following exams and procedures:

• Physical examination of the individual and medical history evaluation
• Nikolsky sign: The physician may rub the skin near the blister to check if the skin peels-off. If it does, it indicates a possibility of pemphigus. A positive Nikolsky sign is seen in other severe skin conditions
• Blood tests: Blood tests are conducted to check the level of desmoglein antibodies in blood. An elevated level of this antibody can help confirm the presence of pemphigus
• Blood tests, analysis of pus, and culture of the fluid being drained may be undertaken, as needed, to check for any infections
• Dermoscopy: Dermoscopy is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Imaging studies of the affected regions, which may include CT and MRI scans
• Skin biopsy: A skin biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Direct and indirect immunofluorescence studies on the skin biopsy specimen: A biopsy positive for antibodies directed against the outer surface of keratinocytes on the surface layer of the skin is the gold standard for the diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Paraneoplastic Pemphigus?

The complications due to Paraneoplastic Pemphigus are usually severe and may include:

• Severe emotional stress and cosmetic issues
• Superimposed bacterial and fungal skin infections
• 1 in 3 individuals are known to have bronchiolitis obliterans syndrome, a lung condition that causes severe respiratory issues, including asphyxiation
• Malnutrition due to difficulty in eating
• Blood disorders:
  • Autoimmune cytopenia - resulting in decreased number of red blood cells, white blood cells, and platelets causing a variety of signs and symptoms
  • Severe anemia resulting in signs and symptoms such as fatigue, pale skin, shortness of breath, and dizziness
  • Severe reduction in white blood cells causing frequent infections
  • Severe reduction in platelet count (thrombocytopenia) resulting in signs and symptoms such as severe headaches, easy bruising, blood in stool/vomit, and heavy menstruation
• Sepsis or blood infection
• Severe involvement of various organs such as the thyroid gland, kidney, and gastrointestinal tract
• Multi-organ damage and failure
• Overall decreased quality of life
• Treatment complications and medication side effects

Additionally, severe complications from the underlying malignancy may be noted, which may include the spread of cancer to other sites (metastasis).

How is Paraneoplastic Pemphigus Treated?

Undertaking prompt and adequate treatment of the underlying malignancy/cancer is crucial in managing Paraneoplastic Pemphigus. This may include radiation therapy, chemotherapy, and surgery, depending on the nature of the diagnosed malignant tumor.

The treatment measures available for the skin lesions include:

• Topical and systemic corticosteroids
• Systemic immunosuppressant medications
• Undertaking treatment of any secondary infections through administration of antibiotic or antifungal agents
• Good skin care and general body hygiene is important

Regular follow up visits with the healthcare provider is important and highly recommended.

How can Paraneoplastic Pemphigus be Prevented?

It may not be possible to currently prevent Paraneoplastic Pemphigus. A prevention of the condition involves an early diagnosis and appropriate treatment of the underlying benign/malignant tumor.

What is the Prognosis of Paraneoplastic Pemphigus? (Outcomes/Resolutions)

The prognosis of Paraneoplastic Pemphigus (PNP) is generally poor due to association with the underlying malignancy.

• PNP is associated with high mortality rates (nearly 90%) due to severe complications and multi-organ involvement
• Deaths are known to occur from lung failure (severe respiratory distress), sepsis, or multiorgan failure

Additional and Relevant Useful Information for Paraneoplastic Pemphigus:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/