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Drug-Induced Pemphigus

Updated : August 24, 2023





Background

A rare collection of bullous autoimmune illnesses that affect the skin & mucous membranes are collectively referred to as pemphigus. The presence of extensive flaccid lesions & erosions emerging on the skin & oral cavity is the classic pemphigus presentation.

A mixture of biochemical processes, as well as inappropriate activation of host B cells that produce internalized IgG autoantibodies, results in medication-induced pemphigus.

These antibodies damage the desmogleins, leading to acantholysis or the separation of the epidermis cells. Despite the fact that a number of things have been identified as pemphigus triggers, medicines remain the main culprit.

Epidemiology

Pemphigus is a rare condition that affects 1 in 100,000 persons, according to estimates. Despite the possibility of multiple causes, medication-induced pemphigus is the most typical one. The most prevalent variety, pemphigus Vulgaris, with a frequency of 0.1 – 0.5 in 100,000 people. Additionally, the incidence of pemphigus Vulgaris is higher among Jews and people of Mediterranean ancestry.

With an average age between 40 and 60 years, there appears to be an equal occurrence in both females and males. The most often used illicit substances include penicillin, captopril, & D-penicillamine. According to one study, the incidence among people who have taken penicillamine for the past 6 months was as great as 7%.

Anatomy

Pathophysiology

Pemphigus brought on by drugs is probably the result of metabolic and immune processes. It has been discovered that some stimulating substances’ chemical makeup affects how well cells adhere to one another. Medication-induced pemphigus has also been linked to intracellular autoantibodies. The most frequent pemphigus-causing substances, thiol medications, have been found to encourage acantholysis by chemically interacting with the keratinocyte cell wall.

A disulfide bond may form as a result of a drug’s interaction with the thiol subgroup, which would prevent cell-to-cell binding and lead to acantholysis. The induction of plasmin and the stimulation of proteolytic enzymes are two other hypothesized pathways for biochemical acantholysis. It has been demonstrated that the stimulation of plasminogen activator blockers is impaired by both penicillamine & captopril.

Additionally, medications cause pemphigus by causing immunological acantholysis and the development of IgG autoantibodies targeting desmogleins 1 and 3. The primary glycoprotein of cadherins, which contributes to the structural components of desmosomes, is desmoglein. Desmosomes aid in the fusion of nearby keratinocytes.

Etiology

Pemphigus has a number of recognized triggers, although medications are still the most common cause of the condition. Based on their chemical makeup, the inciting pharmaceuticals can be divided into three primary categories: thiols medicines, phenol medicines, & phenol/non-thiol medicines. Thiol medications are recognized to be the most frequent cause of pemphigus because they feature a sulfhydryl (-SH) component in their chemical composition.

Penicillamine, troponin, & captopril are a few of the notable thiols that have been implicated in the development of pemphigus. According to the literature, thiol medicines encourage acantholysis by blocking keratinocyte aggregation-promoting enzymes & activating keratinocyte-disaggregating enzymes like plasminogen activators.

Phenol medications cause keratinocytes to secrete proinflammatory mediators, which compromises the integrity of cell adhesion systems. The activation of complement & proteases, which results in acantholysis, is triggered by the release of tumor necrosis factor-alpha & interleukin-1 from cell lines. The most notable phenols are levodopa, heroin, aspirin, rifampin, and so forth.

Numerous medications that are not thiol- nor phenol-based have also been traditionally described in pemphigus. These substances may also activate autoantibodies or change the structure of the specific protein on keratinocytes in order to produce acantholysis. Calcium-channel inhibitors & non-steroid anti-inflammatory medications are a few examples of these medications.

 

Genetics

Prognostic Factors

Patients with pemphigus caused by thiol medications who don’t have cellular autoantibodies have a fair prognosis. Upon stopping the thiol medication, at minimum, 50 percent of patients will experience improvement. Unfortunately, cellular autoantibodies are present in a large proportion of patients with drug-induced pemphigus, and these people will experience a chronic course resembling pemphigus Vulgaris.

Although drug-induced pemphigus fatality rates are unknown, there have been a few reported isolated deaths. However, chronic pemphigus has a higher mortality rate as well as a poor quality of life when it persists. The majority of patients experience pain and burning skin lesions that are typically quite large. Involvement of the oral cavity might result in a reduction in oral ingestion, dehydration, and severe loss of weight.

Clinical History

Clinical History

Whether thiol and non-thiol medications were used to cause the drug-induced pemphigus will affect the clinical characteristics.

Pemphigus foliaceus is brought on by thiol medications.

  • Plaques that are erythematous, scaly, or crusty are how Pemphigus foliaceus manifests.
  • There may or may not be erosions, bullae, and vesicles.
  • No oral mucosa is affected.
  • The trunk is the area most frequently impacted.

Pemphigus Vulgaris is most frequently brought on by non-thiol medications.

  • Bullae and flaccid vesicles that are painful are the hallmarks of pemphigus Vulgaris.
  • The scalp, trunk, and face are all impacted.
  • The oral mucosa may be impacted by the blistering.

Physical Examination

Physical Examination

Depending on the underlying pathomechanism, drugs can cause pemphigus with different clinical symptoms. Thiol drug-induced disease frequently exhibits pemphigus foliaceus-like clinical symptoms.

Plaques that are erythematous, scaly, and crusty mostly affect the trunk. Bullae and superficial vesicles are occasionally visible; however, they typically burst. No oral lesions happen.

Pemphigus caused by non-thiol drugs typically manifests as pemphigus Vulgaris. Erosions and flaccid bullae can arise on both the oral mucosa and seemingly healthy skin.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

Pemphigus Vulgaris

Paraneoplastic Pemphigus

Pemphigus foliaceus

Pemphigus Erythematosus

Pemphigus Herpetiformis

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Stopping the causative agent and using immunosuppressants and immunomodulators to squelch the host autoimmune reaction constitute the cornerstones of treatment. Systemic corticosteroids should be used vigorously and promptly to induce pemphigus at a dosage of 1 mg/kg weight. Systemic corticosteroids should be used vigorously and promptly to induce pemphigus at a dosage of 1 mg/kg weight. In cases of severe illness, immunosuppressive medications, including methotrexate, mycophenolate mofetil, azathioprine, and cyclophosphamide, are also utilized.

By concentrating on the abnormal B cells, the anti-CD-20 antibody rituximab has also demonstrated promise as a treatment for refractory pemphigus. Some cases also point to a worsening of the condition following rituximab therapy. Despite the absence of well-controlled clinical research on the optimal management of medication-induced pemphigus, corticosteroids and also immunosuppressive medication like azathioprine remain to be the cornerstone of treatment.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

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References

https://www.ncbi.nlm.nih.gov/books/NBK499864/

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Drug-Induced Pemphigus

Updated : August 24, 2023




A rare collection of bullous autoimmune illnesses that affect the skin & mucous membranes are collectively referred to as pemphigus. The presence of extensive flaccid lesions & erosions emerging on the skin & oral cavity is the classic pemphigus presentation.

A mixture of biochemical processes, as well as inappropriate activation of host B cells that produce internalized IgG autoantibodies, results in medication-induced pemphigus.

These antibodies damage the desmogleins, leading to acantholysis or the separation of the epidermis cells. Despite the fact that a number of things have been identified as pemphigus triggers, medicines remain the main culprit.

Pemphigus is a rare condition that affects 1 in 100,000 persons, according to estimates. Despite the possibility of multiple causes, medication-induced pemphigus is the most typical one. The most prevalent variety, pemphigus Vulgaris, with a frequency of 0.1 – 0.5 in 100,000 people. Additionally, the incidence of pemphigus Vulgaris is higher among Jews and people of Mediterranean ancestry.

With an average age between 40 and 60 years, there appears to be an equal occurrence in both females and males. The most often used illicit substances include penicillin, captopril, & D-penicillamine. According to one study, the incidence among people who have taken penicillamine for the past 6 months was as great as 7%.

Pemphigus brought on by drugs is probably the result of metabolic and immune processes. It has been discovered that some stimulating substances’ chemical makeup affects how well cells adhere to one another. Medication-induced pemphigus has also been linked to intracellular autoantibodies. The most frequent pemphigus-causing substances, thiol medications, have been found to encourage acantholysis by chemically interacting with the keratinocyte cell wall.

A disulfide bond may form as a result of a drug’s interaction with the thiol subgroup, which would prevent cell-to-cell binding and lead to acantholysis. The induction of plasmin and the stimulation of proteolytic enzymes are two other hypothesized pathways for biochemical acantholysis. It has been demonstrated that the stimulation of plasminogen activator blockers is impaired by both penicillamine & captopril.

Additionally, medications cause pemphigus by causing immunological acantholysis and the development of IgG autoantibodies targeting desmogleins 1 and 3. The primary glycoprotein of cadherins, which contributes to the structural components of desmosomes, is desmoglein. Desmosomes aid in the fusion of nearby keratinocytes.

Pemphigus has a number of recognized triggers, although medications are still the most common cause of the condition. Based on their chemical makeup, the inciting pharmaceuticals can be divided into three primary categories: thiols medicines, phenol medicines, & phenol/non-thiol medicines. Thiol medications are recognized to be the most frequent cause of pemphigus because they feature a sulfhydryl (-SH) component in their chemical composition.

Penicillamine, troponin, & captopril are a few of the notable thiols that have been implicated in the development of pemphigus. According to the literature, thiol medicines encourage acantholysis by blocking keratinocyte aggregation-promoting enzymes & activating keratinocyte-disaggregating enzymes like plasminogen activators.

Phenol medications cause keratinocytes to secrete proinflammatory mediators, which compromises the integrity of cell adhesion systems. The activation of complement & proteases, which results in acantholysis, is triggered by the release of tumor necrosis factor-alpha & interleukin-1 from cell lines. The most notable phenols are levodopa, heroin, aspirin, rifampin, and so forth.

Numerous medications that are not thiol- nor phenol-based have also been traditionally described in pemphigus. These substances may also activate autoantibodies or change the structure of the specific protein on keratinocytes in order to produce acantholysis. Calcium-channel inhibitors & non-steroid anti-inflammatory medications are a few examples of these medications.

 

Patients with pemphigus caused by thiol medications who don’t have cellular autoantibodies have a fair prognosis. Upon stopping the thiol medication, at minimum, 50 percent of patients will experience improvement. Unfortunately, cellular autoantibodies are present in a large proportion of patients with drug-induced pemphigus, and these people will experience a chronic course resembling pemphigus Vulgaris.

Although drug-induced pemphigus fatality rates are unknown, there have been a few reported isolated deaths. However, chronic pemphigus has a higher mortality rate as well as a poor quality of life when it persists. The majority of patients experience pain and burning skin lesions that are typically quite large. Involvement of the oral cavity might result in a reduction in oral ingestion, dehydration, and severe loss of weight.

Clinical History

Whether thiol and non-thiol medications were used to cause the drug-induced pemphigus will affect the clinical characteristics.

Pemphigus foliaceus is brought on by thiol medications.

  • Plaques that are erythematous, scaly, or crusty are how Pemphigus foliaceus manifests.
  • There may or may not be erosions, bullae, and vesicles.
  • No oral mucosa is affected.
  • The trunk is the area most frequently impacted.

Pemphigus Vulgaris is most frequently brought on by non-thiol medications.

  • Bullae and flaccid vesicles that are painful are the hallmarks of pemphigus Vulgaris.
  • The scalp, trunk, and face are all impacted.
  • The oral mucosa may be impacted by the blistering.

Physical Examination

Depending on the underlying pathomechanism, drugs can cause pemphigus with different clinical symptoms. Thiol drug-induced disease frequently exhibits pemphigus foliaceus-like clinical symptoms.

Plaques that are erythematous, scaly, and crusty mostly affect the trunk. Bullae and superficial vesicles are occasionally visible; however, they typically burst. No oral lesions happen.

Pemphigus caused by non-thiol drugs typically manifests as pemphigus Vulgaris. Erosions and flaccid bullae can arise on both the oral mucosa and seemingly healthy skin.

Differential Diagnoses

Pemphigus Vulgaris

Paraneoplastic Pemphigus

Pemphigus foliaceus

Pemphigus Erythematosus

Pemphigus Herpetiformis

Stopping the causative agent and using immunosuppressants and immunomodulators to squelch the host autoimmune reaction constitute the cornerstones of treatment. Systemic corticosteroids should be used vigorously and promptly to induce pemphigus at a dosage of 1 mg/kg weight. Systemic corticosteroids should be used vigorously and promptly to induce pemphigus at a dosage of 1 mg/kg weight. In cases of severe illness, immunosuppressive medications, including methotrexate, mycophenolate mofetil, azathioprine, and cyclophosphamide, are also utilized.

By concentrating on the abnormal B cells, the anti-CD-20 antibody rituximab has also demonstrated promise as a treatment for refractory pemphigus. Some cases also point to a worsening of the condition following rituximab therapy. Despite the absence of well-controlled clinical research on the optimal management of medication-induced pemphigus, corticosteroids and also immunosuppressive medication like azathioprine remain to be the cornerstone of treatment.

https://www.ncbi.nlm.nih.gov/books/NBK499864/

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