Introduction:
The term pemphigus originates from the Greek word ‘pemphix,’ which means blister or bubble. Therefore, this may be definable as a group of chronic blistering diseases of the skin or the epithelial layers. Pemphigus disease mainly occurs due to the production of IgG autoantibodies against the domains of cell membrane proteins, especially cells called keratinocytes resulting in the loss of cellular adhesion (the phenomenon of acantholysis).
What Are the Types of Pemphigus?
Pemphigus has three major subtypes:
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Pemphigus Vulgaris.
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Pemphigus foliaceus.
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Paraneoplastic pemphigus.
A. Pemphigus Vulgaris: in this subtype, the blisters develop deep in the epidermal or oral epithelium above the basal layer when observed histologically. Pemphigus Vulgaris clinically manifests as a mucosally dominant variety with multiple mucocutaneous lesions that start in the oral mucosa classically. These lesions further extend to the skin. In the oral mucosa, the manifestation of flaccid blisters and prone to rupture are characteristic signs of this disease. These lesions can be painful, erosive, and occur more frequently in the buccal mucosal region. Weight loss and malnutrition are other physical features seen with the onset of the disease. Apart from the oropharyngeal mucosal disease, other mucous membranes are involved, including the lining of the larynx, esophagus, conjunctiva, nose, genitalia, anus, etc. Lesions of the skin may extend to or involve the head, upper trunk, and groin regions accompanied by crusted erosive lesions or erythematous skin, or both.
B. Pemphigus Foliaceus: In this subtype, the pemphigus foliaceus blisters occur in the superficial layers of the epidermis. In pemphigus foliaceus, it not only affects mucosal areas. Patients may clinically present with multiple scaly and crusted erosive lesions that are flaky or seen as circumscribed patches on the skin.
C. Paraneoplastic Pemphigus is different from the previous two subtypes by the presence of underlying or associated neoplasms. Mostly these neoplasms may be of lymphoid tissue origin.
What Are the Etiology and Pathogenesis of Pemphigus?
The onset and etiology of this disease are linked to the age group, usually in the fifth to sixth decade of life. Women are more affected than men comparatively in the incidence groups observed generally. Most patients who manifest clinical symptoms are usually between 50 to 60 years of age. Increased prevalence of low titers of disease-associated serum autoantibodies can be traced according to research and documented evidence in first-degree relatives of some patients suffering from pemphigus. This proves that there is a possibility of definite genetic transmission or linkage. HLA alleles are also identified as risk factors for genetic transmission, but the correlation between specific HLA genes and the patient’s clinical features remains elusive.
However, other factors apart from genetics that would trigger the potential onset of pemphigus like environmental determinants, drugs containing a thiol group or metal chelating agents like Penicillamine, other medications like Captopril, etc., have been hypothesized to interfere with the biochemistry of the keratinocyte membrane mechanism causing a disturbance of immune balance. This phenomenon, in turn, leads to the promotion of acantholysis that causes pemphigus.
Other environmental factors researched as triggers for disease onset are viral infections due to herpes simplex virus, dietary factors, physiological or psychological stressor mechanisms.
How to Diagnose Pemphigus Vulgaris?
On physical examination, apart from the clinical features, patients manifest positive Nikolsky signs in the active phase of the disease. Therefore, the lesional biopsy is a reliable method to detect pemphigus Vulgaris.
Histopathologically a ‘tombstone effect’ can be observed microscopically, which is the presence of residual basal keratinocytes at the basement membrane zone, which might be seen on the floor of the blister.
Direct immunofluorescence microscopy of lesional biopsy specimens obtained would prove a reliable and sensitive diagnostic test for detecting any three forms of pemphigus.
The desmoglein ELISA test is particular in sensitivity and specificity for detecting pemphigus. Patients suffering from pemphigus have circulating anti-desmoglein antibodies that do not occur otherwise in typically healthy individuals. Western blotting or immunoprecipitation of epithelial cells and other methods like obtaining keratinocyte extracts may not be practical in diagnosing pemphigus vulgaris and pemphigus foliaceus but are often used to identify non-desmoglein target proteins in patients suffering from the third subtype, i.e., the paraneoplastic pemphigus lesions.
What Are the Differential Diagnoses of Pemphigus?
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Autoimmune Diseases: bullous pemphigoid, mucous membrane pemphigoid, lichen planus, epidermolysis bullosa, bullous dermatosis, bullous lupus erythematosus, etc.
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Underlying Disease or Syndrome: aphthous stomatitis, erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis /TENS syndrome, lichen planus, Grover disease, seborrheic dermatitis, pustular dermatosis.
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Infectious Diseases: staphylococcal infections, bullous impetigo, acute herpetic stomatitis, etc.
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Certain Genetic Diseases.
How to Manage Pemphigus?
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The first-line treatment or gold standard for initial reduction of the disease and reducing mortality risk is systemic corticosteroid therapy owing to its rapid effects.
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In addition, topical and intralesional corticosteroids can be used as adjunctive therapy or monotherapy in localized mild diseases.
The following are all other adjuvant or accessory medications, techniques, and therapies that would be instituted by the physician based upon the mortality risk and extent of pemphigus infection in the affected individual. It includes:
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Osteoporosis counseling is also provided if the corticosteroid treatment lasts for the patient for more than three months to counteract the issue of bone resorption and fragility.
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Intravenous immunoglobulin therapy,
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Rituximab therapy,
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The use of steroid-sparing agents or immunosuppressive agents like Cyclosporine,
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New age techniques like plasmapheresis (that involves the plasma exchange with albumin or the fresh frozen plasma forms), immunoadsorption method to remove serum antibodies in case of severe or refractory pemphigus.
Osteoporosis counseling is also provided if the corticosteroid treatment lasts for the patient for more than three months to counteract the issue of bone resorption and fragility.
The reported mortality risk due to the side effects of long-term pemphigus treatment includes respiratory tract infections, life-threatening sepsis or septicemia, cardiovascular disease, and peptic ulcer disease.
Conclusion:
To conclude, pemphigus vulgaris and pemphigus foliaceus are more associated with risks of morbidity and mortality. However, mortality has now, in recent decades, decreased due to the advancements in therapeutic and regular use of corticosteroids and adjuvant immunosuppressants based on timely diagnosis and treatment planning by the physician.
