The biological gray zone in dermatologic laser and energy-based procedures: From intended photobiomodulation to paradoxical effects

Dermatologic lasers and energy-based devices can produce biological responses ranging from intentional non- destructive modulation to target destruction. This narrative review distinguishes intentional photobiomodulation and low-fluence pigment modulation from an author-defined concept termed target-relative sub-therapeutic exposure: an effective dose at a specified target that is insufficient to achieve the intended therapeutic endpoint. The definition is not based on nominal fluence alone; it integrates wavelength-chromophore coupling, pulse duration, target depth and thermal kinetics, spot size, cooling, spatial delivery, repetition, cumulative exposure and host factors. Paradoxical hypertrichosis after laser or intense pulsed light hair removal is the strongest clinical anchor for an unintended paradoxical response, although its pathogenesis is multifactorial and remains uncertain. Target-relative underexposure is proposed as one potential pathway rather than an established cause. Mechanistic plausibility is informed by sublethal thermal stress, HSP70-associated thermotolerance, cooling physics and spatial fluence heterogeneity, while host susceptibility and inflammation represent important competing or interacting mechanisms. Photobiomodulation is discussed as an intentional comparator, and home- use hair-removal devices are judged by whether the intended follicular endpoint is achieved rather than by low nominal fluence. Low-fluence laser toning is likewise intentional when its aim is subcellular pigment modulation, although cumulative exposure can produce dyspigmentation. The practical framework emphasizes endpoint- guided dosing, target-specific cooling, spatial dose control, test spots and early reassessment.