A Unified Concept of Skin Failure: Primary and Secondary Forms

To the Editor,

We read Levine's review [1] with admiration and agreement. His central observation concerns the conflicting terminology of skin failure. We believe this is correct and timely. The many overlapping terms for skin failure have created confusion. That confusion undermines bedside assessment, documentation, quality measurement, and regulatory consistency. His call for a unified framework, rather than definitions fragmented across specialties, resonates with us and deserves a wider hearing. We write as dermatologists to amplify the primary cutaneous component that a unified concept must have.

Levine's model, which he has also set out with Berlowitz in JAMA Internal Medicine [2], rests largely on one mechanism. In his words, skin failure arises from “the interaction of mechanical tissue deformation with systemic physiologic vulnerability.” This describes secondary skin failure, in which systemic illness, hypoperfusion, inflammation, vascular dysfunction and reduced physiological reserve lead to failure of the skin. Here, the skin is the victim of systemic collapse. Its best‐known consequence in the wound‐care literature is the Kennedy ulcer: a sacral ulcer appearing abruptly in the days before death [3]. Levine describes this form with great clarity. It is, however, only one face of skin failure.

The other is primary skin failure. Here, skin disease or direct skin damage destroys the skin itself, and the failing skin becomes the driver of systemic illness. Stevens–Johnson syndrome and toxic epidermal necrolysis represent the prototype of acute primary skin failure due to severe cutaneous disease, and burns the prototype due to direct skin damage. These and other causes are summarised in Table 1. In each, the cutaneous barrier fails, thermoregulation collapses and defences against infection are breached. Fluid, protein and heat escape through the damaged surface. The skin is not a bystander. It is the failing organ and the driver of the systemic derangement that follows.

TABLE 1.

Causes of primary skin failure, grouped by category (not exhaustive).

Category	Representative conditions
Severe cutaneous adverse reactions	Stevens–Johnson syndrome/toxic epidermal necrolysis, DRESS (drug reaction with eosinophilia and systemic symptoms), acute generalised exanthematous pustulosis, reactions to immune checkpoint inhibitors and targeted cancer therapies
Inflammatory erythrodermas	Erythrodermic psoriasis, generalised pustular psoriasis, erythrodermic atopic dermatitis, erythroderma of other or unknown cause
Autoimmune blistering diseases	Pemphigus and pemphigoid, linear IgA bullous dermatosis, epidermolysis bullosa acquisita
Infective	Staphylococcal scalded skin syndrome
Neoplastic with erythroderma	Erythrodermic cutaneous T‐cell lymphoma, Sézary syndrome
Primary skin damage (external injury)	Thermal burns, cold injury (frostbite), electrical injury, radiation injury, chemical burns and mechanical skin loss

Abbreviation: IgA, immunoglobulin A.

A unified concept of skin failure must therefore recognise two forms. In primary skin failure, the skin fails first and drives the systemic consequences that follow. In secondary skin failure, systemic disease causes the skin to fail. Both forms may reach the same endpoint: failure of the skin to maintain its vital functions.

The distinction matters in practice. Primary skin failure is often reversible, unlike much of the secondary spectrum. Supportive or palliative care alone is inadequate: the skin must be recognised and treated as an organ in acute failure, alongside treatment of the underlying cutaneous disease or injury. A model centred only on secondary skin failure risks making this reversible emergency invisible.

We therefore endorse Levine's call for consensus, with one addition. Any shared definition, model or coding framework should comprise both forms. The acute, severe dermatological diseases and injuries that cause primary skin failure must be recognised as emergencies and escalated as such, as clearly as burns are [4, 5].

This concern is not hypothetical. Despite dermatology representation, the recent National Pressure Injury Advisory Panel consensus (2025) centred on critical illness, pressure injury and systemic decline, and did not recognise primary skin failure as distinct. Any unified framework must encompass both forms [6].

Primary skin failure is not a new idea. Irvine recognised it as a real entity in 1991 [7]. Inamadar and Palit described it as a dermatological emergency requiring intensive care in 2005 [8]. Melandri and colleagues distinguished it from its secondary counterpart in 2022 [9]. As dermatologists, we feel compelled to support a broader concept of skin failure that recognises intrinsic cutaneous disease and direct skin damage, and to work with other specialties to close this gap.

Levine has valuably begun the search for clarity. That search will be better served if skin failure is allowed to mean everything it should.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.