EL CONCEPTO P-I: UNA NUEVA TEORÍA INMUNOLÓGICA SOBRE LAS REACCIONES CUTÁNEAS ASOCIADAS A FÁRMACOS.

José Manuel Ríos Yuil; Manuel Ríos Castro

Submitted October 20, 2024

Published 2026-03-02

Artículos de Investigación

Vol. 24 No. 1 (2011): Revista Médico Científica

THE P-I CONCEPT: A NEW IMMUNOLOGIC THEORY FOR DRUG RELATED SKIN REACTIONS.

José Manuel Ríos Yuil ⁺⁻
Manuel Ríos Castro⁺⁻

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Published: 2026-03-02

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Abstract

The frequency of drug hypersensitivity reactions with cutaneous involvement is increasing. The severity of the reactions, range from the relatively mild ones to those that endanger the life of the patient. The p-i concept is a new immunologic hypothesis that postulates that certain drugs bind directly, specifically and reversibly to some T cell receptors. Through this mechanism, drugs can induce a hypersensitivity reaction without the need of antigen processing by antigen presenting cells or previous sensitization. The p-i concept was formulated to complement the hapten and prohapten hypotheses and not to replace them. With this concept we can explain the mechanisms of hypersensitivity reactions that start soon after the first administration of certain drugs, and how some viral infections increase the risk of drug hypersensitivity.

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References

Martin T, Li H. Severe cutaneous adverse drug reactions: a review on epidemiology, etiology, clinical manifestation and pathogenesis. Chin Med J (Engl). 2008 Apr 20; 121(8): 756-61.
Hausmann O, Schnyder B, Pichler WJ. Drug hypersensitivity reactions involving skin. Handb Exp Pharmacol. 2010; (196): 29-55.
Segal AR, Doherty KM, Leggott J, Zlotoff B. Cutaneous reactions to drugs in children. Pediatrics. 2007 Oct; 120(4): e1082-96.
Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology. 2005 Apr 15; 209(2): 123-9.
Shiohara T, Mizukawa Y. Fixed drug eruption: a disease mediated by self-inflicted responses of intraepidermal T cells. Eur J Dermatol. 2007 May-Jun; 17(3): 201-8.
Ismail SB, Kumar SK, Zain RB. Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci. 2007 Jun; 49(2): 89-106.
Hammerbeck AA, Daniels NH, Callen JP. Ioversol-induced acute generalized exanthematous pustulosis: a case report. Arch Dermatol. 2009 Jun; 145(6): 683-7.
Valeyrie-Allanore L, Roujeau JC. Denominations and classification of severe cutaneous adverse reactions to drugs: splitters versus mergers. Eur J Dermatol. 2007 Sep-Oct; 17(5): 359-60.
Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpes viruses and antiviral and antidrug immune responses. Allergol Int. 2006 Mar; 55(1): 1-8.
Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, et al. Stevens - Johnson syndrome and Toxic Epidermal Necrolysis: Assessment of Medication Risks with emphasis on recently marketed drugs. The EuroSCAR-Study. J Invest Dermatol. 2008 Jan; 128(1): 35-44.
French LE. Toxic epidermal necrolysis and Stevens Johnson Syndrome: Our current understanding. Allergol Int. 2006 Mar; 55(1): 9-16.
Prins C, Kerdel F, Padilla S, Hunziker T, Chimenti S, Viard I, et al. Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases. Arch Dermatol 2003; 139: 26-32.
García Doval I, Roujeau JC, Cruces Prado MJ. Necrolisis epidérmica tóxica y síndrome de Stevens-Johnson: clasificación y actualidad terapéutica. Actas Dermosifiliogr 2000; 91: 541-51.
Molgó M, Carreño N, Hoyos-Bachiloglu R, Andresen M, González S. Use of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis and Stevens-Johnson/toxic epidermal necrolysis overlap syndrome. Review of 15 cases. Rev Méd Chile 2009; 137: 383-9.
Gonzalo-Garijo MA, de Argila D. Erythroderma due to aztreonam and clindamycin. J Investig Allergol Clin Immunol. 2006; 16(3): 210-1.
Schnyder B, Pichler WJ. Mechanisms of drug-induced allergy. Mayo Clin Proc. 2009 Mar; 84(3): 268-72.
Pichler WJ. The p-i concept: pharmacological interaction of drugs with immune receptors. WAO Journal 2008; 1: 96-102.
Roychowdhury S, Svensson CK. Mechanisms of Drug-induced delayed-type hypersensitivity reactions in the skin. AAPS J. 2005 Dec 9; 7(4): E834-46.
Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, et al. Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int. 2006 Mar; 55(1): 17-25.
Gerber BO, Pichler WJ. Noncovalent interactions of drugs with immune receptors may mediate drug-induced hypersensitivity reactions. AAPS J. 2006 Mar 17; 8(1): E160-5.
Pichler WJ (ed): Drug hypersensitivity reactions: classification and relationship to T-cell activation. Basel, Karger, 2007, pp 168-189.
Roujeau JC. Immune mechanisms in drug allergy. Allergol Int. 2006 Mar; 55(1): 27-33.
Tohkin M, Ishiguro A, Kaniwa N, Saito Y, Kurose K, Hasegawa R. Prediction of severe adverse drug reactions using pharmacogenetic biomarkers. Drug Metab Pharmacokinet. 2010; 25(2): 122-33.

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[1] Martin T, Li H. Severe cutaneous adverse drug reactions: a review on epidemiology, etiology, clinical manifestation and pathogenesis. Chin Med J (Engl). 2008 Apr 20; 121(8): 756-61.

[2] Hausmann O, Schnyder B, Pichler WJ. Drug hypersensitivity reactions involving skin. Handb Exp Pharmacol. 2010; (196): 29-55.

[3] Segal AR, Doherty KM, Leggott J, Zlotoff B. Cutaneous reactions to drugs in children. Pediatrics. 2007 Oct; 120(4): e1082-96.

[4] Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology. 2005 Apr 15; 209(2): 123-9.

[5] Shiohara T, Mizukawa Y. Fixed drug eruption: a disease mediated by self-inflicted responses of intraepidermal T cells. Eur J Dermatol. 2007 May-Jun; 17(3): 201-8.

[6] Ismail SB, Kumar SK, Zain RB. Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation. J Oral Sci. 2007 Jun; 49(2): 89-106.

[7] Hammerbeck AA, Daniels NH, Callen JP. Ioversol-induced acute generalized exanthematous pustulosis: a case report. Arch Dermatol. 2009 Jun; 145(6): 683-7.

[8] Valeyrie-Allanore L, Roujeau JC. Denominations and classification of severe cutaneous adverse reactions to drugs: splitters versus mergers. Eur J Dermatol. 2007 Sep-Oct; 17(5): 359-60.

[9] Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpes viruses and antiviral and antidrug immune responses. Allergol Int. 2006 Mar; 55(1): 1-8.

[10] Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, et al. Stevens - Johnson syndrome and Toxic Epidermal Necrolysis: Assessment of Medication Risks with emphasis on recently marketed drugs. The EuroSCAR-Study. J Invest Dermatol. 2008 Jan; 128(1): 35-44.

[11] French LE. Toxic epidermal necrolysis and Stevens Johnson Syndrome: Our current understanding. Allergol Int. 2006 Mar; 55(1): 9-16.

[12] Prins C, Kerdel F, Padilla S, Hunziker T, Chimenti S, Viard I, et al. Treatment of toxic epidermal necrolysis with high-dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases. Arch Dermatol 2003; 139: 26-32.

[13] García Doval I, Roujeau JC, Cruces Prado MJ. Necrolisis epidérmica tóxica y síndrome de Stevens-Johnson: clasificación y actualidad terapéutica. Actas Dermosifiliogr 2000; 91: 541-51.

[14] Molgó M, Carreño N, Hoyos-Bachiloglu R, Andresen M, González S. Use of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis and Stevens-Johnson/toxic epidermal necrolysis overlap syndrome. Review of 15 cases. Rev Méd Chile 2009; 137: 383-9.

[15] Gonzalo-Garijo MA, de Argila D. Erythroderma due to aztreonam and clindamycin. J Investig Allergol Clin Immunol. 2006; 16(3): 210-1.

[16] Schnyder B, Pichler WJ. Mechanisms of drug-induced allergy. Mayo Clin Proc. 2009 Mar; 84(3): 268-72.

[17] Pichler WJ. The p-i concept: pharmacological interaction of drugs with immune receptors. WAO Journal 2008; 1: 96-102.

[18] Roychowdhury S, Svensson CK. Mechanisms of Drug-induced delayed-type hypersensitivity reactions in the skin. AAPS J. 2005 Dec 9; 7(4): E834-46.

[19] Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, et al. Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int. 2006 Mar; 55(1): 17-25.

[20] Gerber BO, Pichler WJ. Noncovalent interactions of drugs with immune receptors may mediate drug-induced hypersensitivity reactions. AAPS J. 2006 Mar 17; 8(1): E160-5.

[21] Pichler WJ (ed): Drug hypersensitivity reactions: classification and relationship to T-cell activation. Basel, Karger, 2007, pp 168-189.

[22] Roujeau JC. Immune mechanisms in drug allergy. Allergol Int. 2006 Mar; 55(1): 27-33.

[23] Tohkin M, Ishiguro A, Kaniwa N, Saito Y, Kurose K, Hasegawa R. Prediction of severe adverse drug reactions using pharmacogenetic biomarkers. Drug Metab Pharmacokinet. 2010; 25(2): 122-33.

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