SJS, Myocarditis, Lupus, APS, and VWF: Intersecting Multisystem Disorders Affecting the Heart, Skin, and Hemostasis

By SWA

SJS, Myocarditis, Lupus, APS, VWF, and Adrenal Insufficiency: A Convergence of Multisystem Disorders with Overlapping Risk

Introduction

Multisystem diseases such as Stevens-Johnson Syndrome (SJS), myocarditis, Systemic Lupus Erythematosus (SLE), Antiphospholipid Syndrome (APS), and von Willebrand Factor (VWF) disorders can present with overlapping involvement of the skin, heart, blood vessels, immune system, and endocrine system. Adrenal insufficiency, often overlooked in critically ill patients, may also be a life-threatening complication, especially in the setting of systemic inflammation or steroid withdrawal. This article explores their interrelation, highlighted by a case of phenytoin-induced fatal hypersensitivity reaction.

1. Stevens-Johnson Syndrome (SJS) – Mucocutaneous Hypersensitivity Reaction

Overview

SJS is a rare, immune-mediated skin and mucosal disorder, typically triggered by drugs such as:

  • Antiepileptics (phenytoin, carbamazepine)

  • Antibiotics

  • Allopurinol, NSAIDs

Clinical Features

  • Widespread skin pain and epidermal detachment

  • Mucosal erosions (ocular, oral, genital)

  • Fever, systemic inflammation

  • Onset: 1–3 weeks after drug initiation

2. Myocarditis – Cardiac Inflammation

Causes

  • Infection (e.g., viral)

  • Autoimmune diseases (e.g., lupus)

  • Drug hypersensitivity (as seen with phenytoin)

Symptoms

  • Chest pain, palpitations

  • Hypotension, arrhythmias

  • Heart failure and sudden cardiac arrest

Diagnosis

  • Elevated troponins/BNP

  • Cardiac MRI

  • Biopsy if feasible

3. Lupus (SLE) – Autoimmune Multisystem Disease

Systemic Involvement

  • Skin (malar rash), joints, kidneys, eyes

  • Hematologic: Anemia, thrombocytopenia

  • Cardiac: Pericarditis, myocarditis

  • Endocrine: Possible adrenal involvement (secondary AI)

Overlap with APS and VWF dysfunction

4. Antiphospholipid Syndrome (APS) – Prothrombotic Autoimmune State

Key Features

  • Recurrent venous/arterial thrombosis

  • Pregnancy loss

  • Cardiac complications: Valve disease, myocardial infarction

  • Coexists with lupus in ~40% of cases

5. von Willebrand Factor (VWF) Types 2 and 5 – Hemostatic Dysfunction

VWF Type 2

  • Qualitative defect → dysfunctional VWF

  • Mucosal bleeding risk, platelet adhesion issues

VWF Type 5

  • Rare, variant type—combined secretion and function defect

  • May appear in autoimmune or inflammatory states (e.g., lupus)

  • Possible link to paradoxical bleeding or thrombosis

6. Adrenal Insufficiency (AI) – Endocrine Failure in Critical Illness

Definition

AI occurs when the adrenal glands fail to produce adequate cortisol, critical for stress response, blood pressure regulation, and immune modulation.

Types

  • Primary AI: Adrenal destruction (e.g., Addison’s disease)

  • Secondary AI: Pituitary dysfunction or long-term steroid use

  • Acute AI in critical illness: May be triggered by:

    • Severe inflammation (e.g., SJS/DRESS)

    • Hemodynamic instability

    • Abrupt withdrawal of corticosteroids

Clinical Signs

  • Hypotension unresponsive to fluids/inotropes

  • Hyponatremia, hyperkalemia

  • Fatigue, confusion, vomiting

  • Shock

Relevance in This Case

In the context of SJS and myocarditis, AI should be suspected if hypotension persists despite inotropes. Cortisol deficiency exacerbates cardiovascular collapse and contributes to multi-organ failure.

7. Case Report: Fatal Phenytoin-Induced SJS, Myocarditis, and Suspected Adrenal Crisis

Patient Presentation

  • Started on phenytoin (Zentropil) for seizures

  • Developed fever, mucosal erosions, rash, hypotension

  • Labs: Normal LFTs, APTT 32s, platelets 143,000/mm³

  • GCS 4/15, ventilator-dependent, renal dysfunction

Management

  • Inotropes, IV hydrocortisone 100 mg (possibly for adrenal support)

  • Phenytoin discontinued, switched to sodium valproate

  • Despite support, suffered two cardiac arrests; died within 18 hours

Suspected Adrenal Involvement

  • Persistent hypotension despite fluids and vasopressors

  • High stress state without endogenous cortisol compensation

  • Adrenal insufficiency likely contributed to poor outcome












9. Conclusion

This case highlights the complex interplay between drug hypersensitivity, autoimmune dysfunction, hemostatic imbalance, and endocrine failure:

  • Phenytoin-induced hypersensitivity can cause both SJS and myocarditis, with possible adrenal suppression.

  • APS and lupus increase the risk of cardiac, vascular, and coagulopathic complications

  • VWF type 2 or 5 abnormalities can worsen bleeding in mucosal or inflammatory lesions

  • Adrenal insufficiency should be considered early in critically ill patients with persistent hypotension, particularly in immune-mediated syndromes.

Until now, we do not fully understand how certain medications provoke such severe multi-organ toxicity. Immune genetics, endothelial injury, hormonal axis disruption, and coagulation system anomalies all contribute.

The most common trigger for Stevens-Johnson Syndrome (SJS) is a reaction to certain medications, particularly anticonvulsants, antibiotics, and anti-inflammatory drugs. Other potential triggers include infections, like Mycoplasma pneumoniae, and even certain vaccinations.

Medications:

 Anticonvulsants: Lamotrigine, carbamazepine, and phenytoin are frequently implicated.

Antibiotics: Sulfonamides, such as trimethoprim-sulfamethoxazole, are common culprits.

Anti-inflammatory drugs: NSAIDs, especially oxicams, have been linked to SJS.

Other medications: Allopurinol (used for gout), and nevirapine (used for HIV) can also trigger SJS.

Infections:

Viral infections like herpes, mumps, and flu have been associated with SJS, particularly in children.

Mycoplasma pneumoniae infection can also trigger the condition.

Other factors:

Vaccinations, cancer, systemic diseases, and external chemical exposure have also been linked to SJS.

Genetic factors, like specific human leukocyte antigen (HLA) types, may increase susceptibility.


Reference:

Stevens-Johnson Syndrome After Immunization With Smallpox, Anthrax, and Tetanus Vaccines https://www.mayoclinicproceedings.org/article/S0025-6196(11)62605-0/fulltext

Stevens-Johnson Syndrome https://www.ncbi.nlm.nih.gov/books/NBK459323/

Recurrent Stevens–Johnson syndrome in a patient with systemic lupus erythematosus: a case report:
https://pmc.ncbi.nlm.nih.gov/articles/PMC7585900/

Phenytoin-induced Stevens–Johnson syndrome with myocarditis: a rare case report:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5513850/

What drugs by mitochondria?
https://swaresearch.blogspot.com/2024/01/what-drugs-can-damage-mitochondria.html

Personal experience after mRNA vaccine  incl. images:
Toxic Skin Condition Post-mRNA COVID-19 Vaccination:
https://swaresearch.blogspot.com/2024/06/stevens-johnson-syndrome-and-toxic.html












© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742













































 

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