Symptoms of Paraneoplastic Pemphigus PNP

Clinical Presentations and Symptoms of Paraneoplastic Pemphigus (PNP):

Paraneoplastic Pemphigus (PNP) is a rare and complex autoimmune blistering disorder with a strong association with underlying malignancies. Understanding the diverse clinical presentations and symptoms of PNP is paramount for early diagnosis and management. In this article, we embark on an exploration of the multifaceted world of PNP, shedding light on the diverse ways it manifests.

Clinical Subtypes of PNP

PNP reveals itself in various clinical subtypes, each characterized by distinct features. These subtypes include:

1. Pemphigus-like Presentation

Clinical Features:

• Superficial vesicles
• Flaccid blisters
• Crusted erosions

Histopathology:

• Intraepidermal and/or suprabasal acantholysis
• Surrounding mononuclear cells

2. Pemphigoid-like Presentation

Clinical Features:

• Scaling erythematous papules
• Tense blisters

Histopathology:

• Dyskeratosis with subepidermal splitting
• With or without basal cell vacuolization
• Sparse mononuclear infiltrate at the dermal-epidermal junction

3. Erythema Multiforme-like Presentation

Clinical Features:

• Scaling erythematous papules
• Severe, polymorphic cutaneous or mucosal lesions

Histopathology:

• Dyskeratosis with or without accompanying epidermal acantholysis
• Perivascular infiltrates

4. Graft-versus-Host Disease-like Presentation

Clinical Features:

• Diffuse red, scaly, sometimes dusky, papules

Histopathology:

• Hyper-ortho/parakeratosis
• Variable dyskeratosis
• With or without vacuolar interface change

5. Lichen Planus-like Presentation

Clinical Features:

• Small red to violaceous flat-topped scaly papules

Histopathology:

• Hyperkeratosis
• Lichenoid infiltrate at the dermal-epidermal junction

These clinical subtypes illustrate the versatility of PNP, as patients may present with one or multiple forms of coexisting cutaneous lesions. Additionally, the appearance of psoriasiform and pustular lesions is not unheard of in PNP patients.

Polymorphic Skin Lesions: 

Skin lesions in PNP are anything but uniform and may exhibit varying features even within the same patient. These lesions can often be mistaken for those seen in conditions like pemphigus vulgaris, pemphigus foliaceus, or bullous pemphigoid, affecting virtually any area of the body.

1. Blisters and erosions are frequently observed, mirroring the manifestations of other pemphigus disorders.
2. Blisters can range from confluent, akin to toxic epidermal necrolysis, to erythema multiforme-like targetoid lesions.
3. Lichenoid eruptions present as erythematous papules and plaques, reminiscent of lichen planus and graft-vs.-host disease.
4. In some cases, cutaneous lesions may manifest as onychodystrophy and alopecia. This broad spectrum of skin lesions challenges the diagnostic process but highlights the uniqueness of PNP's clinical presentation.

Extracutaneous Manifestations

While PNP primarily affects the skin and mucous membranes, it can extend its reach to other types of epithelia and internal organs. The extracutaneous manifestations of PNP encompass:

1. Mucostomatitis: Extensive refractory mucostomatitis, often the initial sign of PNP, involves painful mucous membrane erosions, blisters, haemorrhagic crusting, and ulceration in regions like the oropharynx, nasopharynx, conjunctiva, lips, tongue, palate, and genitals.
2. Pruritic Skin Lesions: After mucous membrane involvement, patients frequently develop diffuse polymorphic skin lesions, which are intensely itchy (pruritic).
3. Internal Organ Involvement: PNP can extend its grasp to internal organs such as the lungs, gastrointestinal tract, thyroid gland, and kidneys.
4. Myasthenia Gravis: Some PNP patients exhibit muscle weakness and elevated levels of anti-acetylcholine receptor antibodies, indicative of myasthenia gravis.
5. Bronchiolitis Obliterans: A major cause of mortality in PNP, bronchiolitis obliterans affects approximately 30% of patients, with a higher prevalence among those with Castleman disease. It initially presents as dyspnea and obstructive lung disease.