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Pemphigus Vulgaris is a Rare Autoimmune Skin Disease

Siniša Franjić
Independent Researcher

Article Info

Received Date: 18 January 2025, Accepted Date: 24 January 2025, Published Date: 29 January 2025

*Corresponding author: Siniša Franjić, Independent Researcher.

Citation: Siniša Franjić. (2025). Pemphigus Vulgaris is a Rare Autoimmune Skin Disease. Biomedical and Clinical Research Journal, 1(1); DOI: http;/01.2025/BCRJ/001.

Copyright: © 2025 Siniša Franjić. This is an open-access article distributed under the terms of the Creative Commons Attribution 4. 0 international License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pemphigus vulgaris is a rare autoimmune skin disease. It is a severe chronic, relapsing dermatosis whose lesions may be localized to the skin and/or mucous membranes. Pemphigus vulgaris affects the mucous membranes, which are located in the mouth, throat, nose, eyes, genitals, and lungs. It usually begins with the formation of painful blisters in the mouth and then on the skin. It can occur in people of all races, genders, and age groups. The exact cause of its occurrence is unknown.

Keywords: pemphigus; pemphigus vulgars; blisters; lesions; health

Introduction

There are five main variations of pemphigus: pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus, drug-induced pemphigus, and paraneoplastic pemphigus [1]. Pemphigus (from the Greek pemphix, meaning bubble or rankle) is a uncommon group of immune system, intraepidermal rankling illnesses including the skin and mucous membranes. The gather incorporates pemphigus vulgaris and pemphigus foliaceus. Both were as a rule fatal some time recently glucocorticoid treatment was utilized for their treatment. The contrast between the two disarranges is the level of the epidermis at which acantholysis (misfortune of cohesion of epithelium) happens: the suprabasilar level in pemphigus vulgaris and the subcorneal level in pemphigus foliaceus. Other individuals of the pemphigus bunch are paraneoplastic pemphigus, which for the most part happens in patients with lymphoma, and drug-induced pemphigus, which more often than not creates after taking penicillamine and other drugs.

Pemphigus

Pemphigus is a persistent skin disease which can be quickly lethal if not Rx (mortality 10%) [2]. Oral mucosa is influenced in 95% of patients with pemphigus vulgaris (most common sort) and may be the beginning introduction of pemphigus in 50%. Immune system in aetiology, there are circulating autoantibodies to epithelial desmosome tonofilament. Acantholysis and intercellular IgG &/or C3 are ordinary and cause partition of epithelium over the basal cell layer, and oedema into this potential space produces a shallow, effectively burst, fluid-filled bulla. Burst clears out a huge shallow, effectively contaminated ulcer. The to begin with identifiable injuries are very frequently found in the mouth, particularly on the sense of taste, in spite of the fact that these are more often than not seen as ulcers since the bullae break down quickly. It is basically a infection of center age (F > M). Rarely, it may be drug-induced or paraneoplastic. Other strategies are by histology and coordinate or circuitous immunofluorescent methods (biopsy tests require to be new). Rx: systemic steroids &/or azathioprine, dapsone, mycophenolate mofetil, or gold; also cyclophosphamide, particularly in hard-headed and serious cases. More up to date treatments incorporate biologic specialists (rituximab) and calcineurin inhibitors show up promising.

PV

Pemphigus vulgaris (PV) is a constant immune system rankling disease of the skin and mucous membranes which may be lethal unless treated forcefully [3]. PV is caused by circulating immunoglobulin (Ig)G autoantibodies coordinated against the keratinocyte desmosomal proteins, desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). Dsg1 and 3 play an vital part in cell–cell grip. Official of the autoantibodies to Dsg1 and 3 actuates the misfortune of ordinary cell attachment in the epidermis, and ensuing rankle arrangement. In the mucosal variation, autoantibodies only respond with Dsg3, while patients with the mucocutaneous variation have antibodies against both Dsg1 and 3.

PV influences all races but is more common in people of Jewish and Mediterranean plunge. Hereditary inclination is suspected, since PV happens more regularly with certain major histocompatibility complex (MHC) course II particles, such as DR4 and DRw6. Men and ladies are similarly affected.

PV is the most common variation of pemphigus with an rate of 0.1–0.5 per 100,000 populace [4]. The conclusion of PV is made utilizing four major criteria. These comprise of:

  • Clinical findings
  • Light microscopic findings
  • Direct immunofluorescence findings
  • Indirect immunofluorescence findings

PV is the most common subtype of pemphigus. It is a possibly life-threatening autoimmune

vesiculobullous disorder characterized by nonscarring, delicate vesicles and bullae including the mucosae with shifting cutaneous inclusion. PV ordinarily presents in grown-ups and can influence anyplace in the body but overwhelmingly influences the buccal and labial mucosa. This condition is characterized by Nikolsky’s sign: the application of slight weight on the rankles coming about in their spread to neighboring regions. Histological considers of PV injuries ordinarily illustrate acantholysis in the suprabasilar portion of the epidermis. Commonplace discoveries incorporate IgG and/or C3 official to the intracellular cement substance (ICS) in the mid-lower or whole epidermis of perilesional skin or mucosa on DIF. PV is related with autoantibodies to 130-kDa glycoprotein Dsg3 and auxiliary improvement of antibodies to 160-kDa glycoprotein Dsg1 antigens, when the skin is included. Acetylcholine receptors on keratinocytes have moreover been detailed as a conceivable advance target antigen in PV.

Pemphigus Group

The fundamental pathophysiology of pemphigus is that the circulating IgG autoantibodies repress the cement work of desmogleins (Dsg1 and Dsg3) and cause the misfortune of keratinocyte cell-to-cell attachment (acantholysis in histology), with resultant rankle arrangement [5]. Dsg1 and Dsg3 are cadherin-type cell-to-cell attachment atoms that are communicated in the skin and mucous layers where rankles and disintegrations are found in patients. IgG autoantibodies in pemphigus are recognized in basically all patients with dynamic infection, as decided by coordinate immunofluorescence for in vivo-bound antibodies and by roundabout immunofluorescence or enzyme-linked immunosorbent assay (ELISA) for circulating antibodies. The titers of circulating IgG autoantibodies are ordinarily related with illness activity.

IgG autoantibodies against Dsg1 and Dsg3 are pathogenic and play a essential part in actuating rankle arrangement in pemphigus. Basically, all patients with pemphigus have IgG autoantibodies against Dsg1 and/or Dsg3, depending on the subtype of pemphigus. When antidesmoglein IgG autoantibodies are expelled from the patient’s sera in pemphigus vulgaris,

pemphigus foliaceus, or paraneoplastic pemphigus (PNP) by immunoadsorption with recombinant desmoglein proteins, the sera are no longer pathogenic in the rankle. Besides, antidesmoglein IgG autoantibodies affinity-purified from pemphigus sera on the desmoglein recombinant proteins can cause rankles when infused into neonatal mice. IgG autoantibodies against acetylcholine receptors or annexin-like particles have been detailed, but their pathogenic pertinence in pemphigus remains to be determined.

The net, as well as histological, locales of rankles in pemphigus vulgaris and foliaceus are consistently clarified by desmoglein remuneration hypothesis. For illustration, when sera contain as it were anti-Dsg1 IgG, which meddling with the work of Dsg1, the nearness of Dsg3 compensates for the misfortune of work of Dsg1 in the lower epidermis. In differentiate, in the upper epidermis, there is no recompense by Dsg3; subsequently, rankles as it were show up in the shallow epidermis of the skin. In spite of the fact that the anti-Dsg1 IgG ties to the mucosa, no rankles are shaped since of the co-expression of Dsg 3. Hence, sera containing as it were anti-Dsg1 IgG causes shallow rankles in the skin without mucosal inclusion, as watched in patients with pemphigus foliaceus.

Patients with PNP create characteristic IgG autoantibodies against the different plakin particles that are thought to play a part in tying down keratin fibers to cell membranes, e.g., desmoplakin I, II, BP230, envoplakin, periplakin, and plectin, in expansion to IgG autoantibodies against Dsg3 and/or Dsg1. It is too imperative to bear in intellect that not as it were humoral resistance, but also cell-mediated cytotoxicity, is included in the pathogenesis of PNP, in which more extreme and headstrong verbal disintegrations and stomatitis, as well as more polymorphic skin ejections, are watched compared with classic shapes of pemphigus.

Blisters

Pemphigus vulgaris is the most common frame of pemphigus [3]. Agonizing verbal disintegrations as a rule go before the onset of skin rankles by weeks or months. Association of other mucosal surfaces happens in patients with far reaching infection. The delicate sense of taste was included in 80% of cases at introductory introduction. Nonpruritic flaccid rankles shifting in estimate from 1 cm to a few centimeters show up continuously on ordinary or erythematous skin and may be localized for a significant time. The most common locales are the scalp, confront, axillae, and verbal depth. Rankles perpetually gotten to be generalized if cleared out untreated. The rankles crack effectively since the vesicle roof, which comprises of as it were a lean parcel of the upper epidermis, is delicate. Application of weight to little intaglio bullae causes the liquid to dismember along the side into the midepidermal ranges changed by bound IgG (Nikolsky’s sign).

Exposed disintegrations final for weeks some time recently recuperating with brown hyperpigmentation, but without scarring. Rankles, disintegrations, and lines of erythema may show up in the esophageal mucosa. Death once in the past happened in all cases, more often than not from cutaneous contamination, but presently happens in as it were 10% of cases, as a rule from complications of steroid treatment. Daylight introduction is harmful.

Pemphigus vegetans is a variation of pemphigus vulgaris that presents with expansive verrucous intersecting plaques and pustules localized to flexural zones in the axillae and groin.

Lesions

Typical injuries of PV are flaccid bullae which break effectively and take off stripped, difficult shallow disintegrations that recuperate gradually without scarring [3]. Intaglio bullae are occasionally seen. Commonly, the disease starts in the verbal mucosa with ill-defined, unpredictable, gingival (desquamative gingivitis), buccal, and palatal disintegrations. Other mucosal surfaces may be influenced, counting the conjunctiva, esophagus, vagina, cervix, urethra, and anus. Most patients create cutaneous injuries a few months afterward. Locales of inclination incorporate the scalp, confront, chest, axillae, crotch, and umbilicus. The Nikolsky sign portrays the clinical finding that physical injury can shear the epidermis from normal-appearing skin, coming about in clinical injuries. It is a tolerably delicate but exceedingly particular bedside apparatus for the determination of intraepidermal rankling disarranges, especially pemphigus.

PV includes the female genital tract in up to 50% of patients. Rarely, PV may be localized exclusively to the genital tract. Labia minora are the most as often as possible included location, taken after by the vaginal mucosa, labia majora, and cervix. Genital injuries as a rule hold on indeed when something else fruitful control of generalized pemphigus is accomplished. The resistance to treatment may be clarified by the consistent presentation of the genital tract to nearby injury and grinding from body developments, prophylactic gadgets, tampons, and coitus. Patients with genital illness complain of burning on micturition, distress amid intercut, adherence of underpants to injuries, and foul odor. Interests, a case of PV localized solely to the vaginal mucosa displaying as persistent vaginal release has been reported.

PV of the male genital tract has moreover been depicted, with the glans penis being the most common location of inclusion. The urethral mucosa, with the exemption of the distal parcel, is saved since it is determined from endoderm and needs Dsg1 and 3. Anal and perianal infection is exceptional, but may be experienced in patients with extreme PV.

Neonatal PV

Neonatal PV is an autoimmune infection auxiliary to transplacental transferrance of IgG antibodies [4]. The to begin with neonatal PV case was detailed in 1975 after a woman with PV gave birth to a infant who shown a positive coordinate immunofluorescence recoloring to epidermal acantholytic cells in a Tzanck preparation. Pemphigus antibodies have been recognized in fetal cardiac blood and rope blood in other stillborns.

Pregnancy may accelerate PV or exasperate PV which has been in abatement. The timing of conception ought to likely be focused on to a period of clinical abatement, with moo IF titers and the choice and measurement of maternal medicines ought to take into account conceivable fetal effects.

Patients with PV tend to create their skin injuries amid the to begin with or moment trimester or promptly postpartum. The change of PV amid the third trimester may be due to rising endogenous corticosteroid generation by the chorion and resulting immunosuppression.

Transplacental transmission of maternally determined intercellular substance responsive IgG antibodies to the hatchling, may result in clinical sign of PV in the neonate. This is backed by discoveries of circulating pemphigus antibodies in fetal plasma and its statement in fetal skin, having the characteristic skin injuries of PV.

The serum titer of pemphigus antibodies does not show up to impact neonatal result and there is no positive relationship between seriousness of the maternal illness and the neonatal result. The treatment of choice is verbal corticosteroids and plasmapheresis ought to be saved for extreme cases safe to tall measurements corticosteroid treatment. Since of the noteworthy chance of fetal misfortune, normal fetal checking, along with ultrasonography, is recommended.

Vaginal conveyance is the strategy of choice. In spite of the fact that neighborhood injury supported amid a common conveyance can expand and impede recuperation, Caesarean areas are for the most part disheartened since both the infection handle and corticosteroid treatment can impede wound mending. Breast-feeding is not contraindicated but neighborhood injuries can happen and there is the hypothetical plausibility of inactive exchange of PV IgG antibodies from mother to baby.

Diagnosis

The determination is based on pathologic discoveries, counting skin biopsy appearing a characteristic intraepidermal cleft fair over the basal cell layer, with partition of keratinocytes from one another (acantholysis) [6]. The acantholytic cells line the vesicle and moreover lie free inside the depth. A Tzanck spread from the base of a bulla may appear acantholytic epidermal cells. Coordinate immunofluorescence of normal-appearing skin close a injury appears intercellular IgG and complement statement all through the epithelium. Circuitous immunofluorescence of the patient’s serum illustrates circulating intercellular autoantibodies in approximately 80–90% of patients particular for desmoglein-3 alone when injuries are restricted to the mouth and for both desmoglein-3 and -1 when skin injuries are display in expansion to verbal injuries. Be that as it may, titers of the circulating autoantibodies do not relate with illness seriousness but regularly parallel infection activity.

Fluid, electrolyte, and wholesome unsettling influences may happen but are less articulated than in disarranges including misfortune of the whole thickness of the epidermis (eg, TEN).

Treatment

Standard treatment comprises of high-dose corticosteroids, ideally in combination with a steroid-sparing immunosuppressive operator such as azathioprine, mycophenolate mofetil, or cyclophosphamide [3]. These drugs are as a rule begun at the same time, taken after by a slow decreasing of the corticosteroid and continuation of the steroid-sparing specialist until clinical reduction is gotten. Plasmapheresis is valuable for rapidly diminishing the titers of circulating antibodies and ought to be considered for serious pemphigus that is inert to a combination of systemic corticosteroids and immunosuppressives. Rituximab and high-dose intravenous immunoglobulin (IVIG) are extra viable treatment choices for safe illness. Patients ought to minimize exercises that may cause the rankles to crack, counting contact sports and utilization of nourishments that may bother the verbal mucosa. Patients with genital injuries ought to dodge sexual movement since injury can actuate unused injuries and avoid existing injuries from mending. Day by day topical care is imperative for anogenital malady. Patients are energized to splash in a shower tub with tepid water to which aluminum acetic acid derivation powder and chlorhexidine gluconate have been included. These added substances dry the sobbing injuries and avoid infection.

Systemic Therapy

During a course of systemic medicate treatment, alterations to the treatment regimen to either diminish poisonous quality or increment the clinical reaction to treatment can be made [7]. Combination treatment is a valuable method to offer assistance minimize the hazard of sedate poisonous quality and/or maximize clinical efficacy. When a systemic treatment is started, concomitant topical treatment not as it were makes a difference to control the skin condition until the systemic treatment takes impact, but might moreover offer assistance keep the by and large dosage of the systemic treatment lower than it would be something else. Topical treatment can moreover permit treatment of separated zones of obstinate malady (e.g., a adamant plaque of psoriasis) or minor changes in infection control (e.g., a “breakthrough” rankle of bullous pemphigoid) amid systemic treatment and in this way help in maintaining a strategic distance from raising dosages of systemic drugs. Combining one systemic treatment with two or more other systemic treatments that have synergistic impacts or complementary antagonistic impact profiles can minimize the measurements and toxicities of each sedate. For example, treating psoriasis with the combination of low dosage cyclosporine (<3 mg/kg/day) and low-dose methotrexate (<10 mg/week) permits for picking up clinical control of the illness at measurements regularly lower than the conventional monotherapy measurements of either medicate. Combination treatment inside or between medicate classes can also be utilized to accomplish clinical reaction when monotherapy is ineffectual or as it were in part viable. For illustration, patients with dermatomyositis who do not completely react to single specialist antimalarial treatment with hydroxychloroquine or chloroquine may benefi t from the expansion of quinacrine.

As the primary objective of systemic treatment is control of disease, it makes sense that once disease control is accomplished the doctor endeavors to either discover the least measurements of a given medicine that keeps up clinically satisfactory disease control or bridges systemic treatment to a sedate or combination of drugs with a more favorable side impact profile. The quickness with which a medicine can be decreased or treatment can be bridged depends not as it were on the common history of the condition being treated and the medicine being utilized to treat that infection, but moreover on the patient’s capacity to endure that pharmaceutical. The treatment methodology for pemphigus vulgaris is a great case of this hone. Some time recently the coming of corticosteroids, pemphigus vulgaris was a life-threatening malady. As of now, in any case, complications of systemic treatment (regularly systemic corticosteroids), not the essential disease, are the most common causes of dreariness and mortality related with pemphigus vulgaris. In this way, a sensible calculation for the treatment of pemphigus vulgaris is the acceptance of abatement with systemic corticosteroids and the support of illness control with a steroid sparing agent such as mycophenolate mofetil.

Conclusion

The immune system produces proteins called antibodies. Antibodies usually attack foreign substances. Pemphigus vulgaris occurs when the immune system mistakenly makes antibodies against proteins on healthy skin and mucous membranes. The antibodies destroy the connections between cells, and fluid builds up between the layers of the skin. This leads to blisters and erosions on the skin. The autoimmune mechanism can also be triggered by certain medications, exposure to ultraviolet rays and X-rays, and it can occur at the same time as other autoimmune diseases.

References

  1. Habif, T. P. (2016.): „Clinical Dermatology - A Color Guide to Diagnosis and Therapy, Sixth Edition“, Elsevier Inc., Philadelphia, USA, pp. 647. – 649.
  2. Mitchell, D. A.; Mitchell, L.; McCaul, L. (2014.): „Oxford Handbook of Clinical Dentistry, Sixth Edition“, Oxford University Press, Oxford, UK, pp. 418.
  3. Basko-Plluska, J. L.; Song, J.; Petronic-Rosic, V. (2014.): „Bullous Diseases“ in Mroczkowski, T. F.; Millikan, L. E.; Parish, L. C. (eds):: „Genital and Perianal Diseases - A Color Handbook“, CRC Press, Taylor & Francis Group, Informa Business, Boca Raton, USA, pp. 178. – 179.
  4. Venugopal, S. S.; Murrell, D. F. (2010.): „Diagnosis and Prevention of Bullous Diseases“ in Norman, R. A. (ed): „Preventive Dermatology“, Springer-Verlag London Limited, London, UK, pp. 119. – 122.
  5. Tanikawa, A.; Amagai, M. (2010.): „Acquired Bullous Disease“ in Krieg, T.; Bickers, D. R.; Miyachi, Y. (eds): „Therapy of Skin Diseases - A Worldwide Perspective on Therapeutic Approaches and Their Molecular Basis“, Springer-Verlag Berlin Heidelberg, Berlin, Germany, pp. 389. – 390.
  6. Zipperstein, K. J. (2008.): „Dermatologic Problems in the Intensive Care Unit“ in Bongard, F. S.; Sue, D. Y.; Vintch, J. R. E. (eds): „CURRENT Diagnosis and Treatment Critical Care, Third Edition“, The McGraw-Hill Companies, Inc., New York, USA, pp. 623.
  7. Fox, L. P. (2010.): „Principles of Systemic Therapy“ in Krieg, T.; Bickers, D. R.; Miyachi, Y. (eds): „Therapy of Skin Diseases - A Worldwide Perspective on Therapeutic Approaches and Their Molecular Basis“, Springer-Verlag Berlin Heidelberg, Berlin, Germany, pp. 74.