Correspondence

Paronychia and Pyogenic Granuloma of the Great Toes in Patients Treated with Indinavir

N Engl J Med 1998; 338:1776-1777June 11, 1998

Article

To the Editor:

Forty-two patients infected with human immunodeficiency virus type 1 (HIV-1) (38 men and 4 women) presented with paronychia of the great toes during the period from September 1996 to September 1997. The median age of the patients was 36 years (range, 22 to 64); 36 were homosexuals, 3 were intravenous-drug users, and 3 were heterosexuals with no known risk factors. Thirty-six patients had AIDS.

The mean CD4 lymphocyte count was 255 per cubic millimeter (range, 16 to 892). Plasma HIV RNA was undetectable in 13 patients and ranged from 600 to 10 ⁶ copies per milliliter in the others (Amplicor HIV-1 Monitor assay, Roche; detection limit, 200 copies per milliliter). None of the patients had had prior episodes of psoriasis, paronychia, local trauma, or Kaposi's sarcoma. All 42 patients were receiving triple therapy including indinavir at presentation. Thirty-six patients had previously received combinations of nucleoside analogues, and four had received triple therapy including ritonavir. The median time between the start of indinavir therapy and the onset of the ingrowing toenails was 120 days (range, 30 to 360).

All the patients had paronychia and ingrown nails on the great toes (Figure 1Figure 1Paronychia with Pyogenic Granuloma of the Lateral Nail Fold.). Pyogenic granuloma–like lesions, staphylococcal superinfection, onycholysis, and severe skin dryness were present in 22, 18, 20, and 28 patients, respectively. Fungal cultures were negative. Antibiotic therapy was required in 31 patients, and surgical treatment in 11. In six patients who had periungual lesions for 4 to 13 months, indinavir was withdrawn because of virologic failure (in three cases), digestive side effects (in two), and skin side effects (in one). In three of these patients, complete regression of skin manifestations occurred within 9 to 12 weeks; partial regression was observed in the three other patients.

Pyogenic granuloma of nail folds and skin dryness may develop in patients receiving retinoids.1 In our patients, skin dryness and pyogenic granuloma were also observed. Homologies between the amino acid sequences of retinoic acid–binding protein 1 and the catalytic site of HIV-1 protease have been noted.2 Inhibition of endogenous proteases may explain the initial hypertrophy of the nail fold and the subsequent development of pyogenic granuloma–like lesions.

The 42 patients described here represent 4 percent of the total number of patients receiving indinavir during the same period. The described side effect led to functional impairment in half these patients (21 of 42). The findings in this series suggest a link between indinavir therapy and hypertrophic paronychia. Clinicians should watch for this side effect in patients receiving protease inhibitors.

Fabrice Bouscarat, M.D.
Cécile Bouchard, M.D.
Hôpital Bichat–Claude Bernard, 75018 Paris, France

Damien Bouhour, M.D.
Hôpital de la Croix Rousse, 69317 Lyon, France

2 References

1. 1

   Baran R. Etretinate and the nails (study of 130 cases): possible mechanisms of some side-effects. Clin Exp Dermatol 1986;11:148-152
   CrossRef | Web of Science | Medline

2. 2

   Carr A, Samaras K, Burton S, Freund J, Chisholm DJ, Cooper DA. A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance due to HIV antiretroviral therapy. Presented at the Fifth Conference on Retroviruses and Opportunistic Infections, Chicago, February 1–5, 1998.
   

Citing Articles (37)

Citing Articles

1. 1

   , Mario E. Lacouture, Milan J. Anadkat, René-Jean Bensadoun, Jane Bryce, Alexandre Chan, Joel B. Epstein, Beth Eaby-Sandy, Barbara A. Murphy. (2011) Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Supportive Care in Cancer 19:8, 1079-1095
   CrossRef

2. 2

   B.M. Piraccini, S. Bellavista, C. Misciali, A. Tosti, D. De Berker, B. Richert. (2010) Periungual and subungual pyogenic granuloma. British Journal of Dermatology 163:5, 941-953
   CrossRef

3. 3

   Camille E. Introcaso, Janet M. Hines, Carrie L. Kovarik. (2010) Cutaneous toxicities of antiretroviral therapy for HIV. Journal of the American Academy of Dermatology 63:4, 549-561
   CrossRef

4. 4

   O. Wauters, M. Sabatiello, N. Nikkels-Tassoudji, A. Choffray, B. Richert, G.-E. Piérard, A.F. Nikkels. (2010) Le botryomycome. Annales de Dermatologie et de Vénéréologie 137:3, 238-242
   CrossRef

5. 5

   M. Blanes, I. Belinchón, J. Portilla. (2009) Reacciones cutáneas adversas a fármacos en los pacientes con infección por el VIH en la era TARGA. Actas Dermo-Sifiliográficas 100:4, 253-265
   CrossRef

6. 6

   M. Blanes, I. Belinchón, J. Portilla. (2009) Cutaneous Drug Reactions in HIV-Infected Patients in the HAART Era. Actas Dermo-Sifiliográficas (English Edition) 100:4, 253-265
   CrossRef

7. 7

   David A. de Berker, Bertrand Richert, Edith Duhard, Bianca Maria Piraccini, Josette André, Robert Baran. (2008) Retronychia: Proximal ingrowing of the nail plate. Journal of the American Academy of Dermatology 58:6, 978-983
   CrossRef

8. 8

   Daniel Lee, Constance A Benson, Cora E Lewis, Carl Grunfeld, Rebecca Scherzer. (2007) Prevalence and factors associated with dry skin in HIV infection: the FRAM study. AIDS 21:15, 2051-2057
   CrossRef

9. 9

   Tim R Cressey, Nottasorn Plipat, Federica Fregonese, Kulkanya Chokephaibulkit. (2007) Indinavir/ritonavir remains an important component of HAART for the treatment of HIV/AIDS, particularly in resource-limited settings. Expert Opinion on Drug Metabolism & Toxicology 3:3, 347-361
   CrossRef

10. 10

    Bianca Maria Piraccini, Matilde Iorizzo. (2007) Drug Reactions Affecting the Nail Unit: Diagnosis and Management. Dermatologic Clinics 25:2, 215-221
    CrossRef

11. 11

    MVG Domínguez, VCD Ceballos, RV Costa, TE Lara, VD Florencio. (2007) Paronychia in an HIV-infected patient under nelfinavir therapy. Journal of the European Academy of Dermatology and Venereology 0:0, 070209222700176-???
    CrossRef

12. 12

    Jay Luther, Marshall J Glesby. (2007) Dermatologic Adverse Effects of Antiretroviral Therapy. American Journal of Clinical Dermatology 8:4, 221-233
    CrossRef

13. 13

    SABELA PARADELA, JESÚS DEL POZO, WALTER MARTÍNEZ, BEATRIS FERNÁNDEZ-JORGE, JESÚS RODRIGUEZ-LOZANO, TERESA YEBRA-PIMENTEL, EDUARDO FONSECA. (2007) Pyogenic Granuloma: Satellitosis after Carbon Dioxide Laser Vaporization Resolved with an Intense Pulsed Light System. Dermatologic Surgery 33:1, 104-108
    CrossRef

14. 14

    Caroline Robert, Jean-Charles Soria, Alain Spatz, Axel Le Cesne, David Malka, Patricia Pautier, Janine Wechsler, Catherine Lhomme, Bernard Escudier, Valérie Boige, Jean-Pierre Armand, Thierry Le Chevalier. (2005) Cutaneous side-effects of kinase inhibitors and blocking antibodies. The Lancet Oncology 6:7, 491-500
    CrossRef

15. 15

    Heidi H. Kong, Sarah A. Myers. (2005) Cutaneous effects of highly active antiretroviral therapy in HIV-infected patients. Dermatologic Therapy 18:1, 58-66
    CrossRef

16. 16

    Frederiek Terheggen, Jos Frissen, Hugo Weigel, Ineke Schouten, Kees Brinkman. (2004) Nail, hair and skin hyperpigmentation associated with indinavir therapy. AIDS 18:11, 1612
    CrossRef

17. 17

    Bianca Maria Piraccini, Matilde Iorizzo, Angela Antonucci, Antonella Tosti. (2004) Drug-induced nail abnormalities. Expert Opinion on Drug Safety 3:1, 57-65
    CrossRef

18. 18

    Manuel Ginarte, Elena Losada, Arturo Prieto, Vicente Lorenzo-Zúñiga, Jaime Toribio. (2002) Generalized hair loss induced by indinavir plus ritonavir therapy. AIDS 16:12, 1695-1696
    CrossRef

19. 19

    Robert Baran, Jean-Claude Roujeau. (2002) New millennium, new nail problems. Dermatologic Therapy 15:2, 64-70
    CrossRef

20. 20

    A. E. Colson, P. E. Sax, M. J. Keller, B. K. Turk, P. T. Pettus, R. Platt, P. W. Choo. (2001) Paronychia in Association with Indinavir Treatment. Clinical Infectious Diseases 32:1, 140-143
    CrossRef

21. 21

    Molly S. Stenzel, Charles C.J. Carpenter. (2000) THE MANAGEMENT OF THE CLINICAL COMPLICATIONS OF ANTIRETROVIRAL THERAPY. Infectious Disease Clinics of North America 14:4, 851-878
    CrossRef

22. 22

    Louise Pedneault, Cindy Brothers, Grace Pagano, Paulina Tymkewycz, Jane Yeo, Judith Millard, Anny Fetter. (2000) Safety profile and tolerability of amprenavir in the treatment of adult and pediatric patients with HIV infection. Clinical Therapeutics 22:12, 1378-1394
    CrossRef

23. 23

    Kai Riecke, Thomas G. Schulz, Mehdi Shakibaei, Bernd Krause, Ibrahim Chahoud, Ralf Stahlmann. (2000) Developmental toxicity of the HIV-protease inhibitor indinavir in rats. Teratology 62:5, 291-300
    CrossRef

24. 24

    Andrew Carr, David A Cooper. (2000) Adverse effects of antiretroviral therapy. The Lancet 356:9239, 1423-1430
    CrossRef

25. 25

    &NA;. (2000) Drug-induced nail disorders: prevention is best. Drugs & Therapy Perspectives 16:1, 13-16
    CrossRef

26. 26

    Jes??s Garc??a-Silva, Manuel Almagro, Javier Juega, Carmen Pe??a, Soledad L??pez-Calvo, Jes??s del Pozo, Eduardo Fonseca. (2000) Protease inhibitor-related paronychia, ingrown toenails, desquamative cheilitis and cutaneous xerosis. AIDS 14:9, 1289
    CrossRef

27. 27

    E. DaudÉn, M. Pascual-LÓpez, C. MartÍnez-GarcÍa, A. GarcÍa-DÍez. (2000) Paronychia and excess granulation tissue of the toes and finger in a patient treated with indinavir. British Journal of Dermatology 142:5, 1063-1064
    CrossRef

28. 28

    J Lenhard. (2000) Stimulation of vitamin A1 acid signaling by the HIV protease inhibitor indinavir. Biochemical Pharmacology 59:9, 1063-1068
    CrossRef

29. 29

    M. Heim, J. Schapiro, M. Wershavski, U. Martinowitz. (2000) Drug-induced and traumatic nail problems in the haemophilias. Haemophilia 6:3, 191-194
    CrossRef

30. 30

    Fabrice Bouscarat, Eve Maubec, Sophie Matheron, Vincent Descamps. (2000) Immune recovery inflammatory folliculitis. AIDS 14:5, 617-618
    CrossRef

31. 31

    I. Panse, E. Vasseur, M.L. Raffin-Sanson, F. Staroz, E. Rouveix, P. Saiag. (2000) Lipodystrophy associated with protease inhibitors. British Journal of Dermatology 142:3, 496-500
    CrossRef

32. 32

    Hélène Peyriere, Jean-Marc Mauboussin, Isabelle Rouanet, Pierre Rouveroux, Dominique Hillaire-Buys, Pierre Balmes. (1999) Frozen shoulder in HIV patients treated with indinavir: report of three cases. AIDS 13:16, 2305
    CrossRef

33. 33

    Yazid Bourezane, Bernard Thalamy, Jean-François Viel, Karine Bardonnet, Christine Drobacheff, Helder Gil, Dominique-Angèle Vuitton, Bruno Hoen. (1999) Ingrown toenail and indinavir: case-control study demonstrates strong relationship. AIDS 13:15, 2181
    CrossRef

34. 34

    Bouscarat, Fabrice, Prevot, Marie-Hélène, Matheron, Sophie, . (1999) Alopecia Associated with Indinavir Therapy. New England Journal of Medicine 341:8, 618-618
    Full Text

35. 35

    Tosti, Piraccini, D'antuono, Marzaduri, Bettoli. (1999) Paronychia associated with antiretroviral therapy. British Journal of Dermatology 140:6, 1165-1168
    CrossRef

36. 36

    SR Porter, C Scully. (1998) HIV topic update: protease inhibitor therapy and oral health care. Oral Diseases 4:3, 159-163
    CrossRef

37. 37

    &NA;. (1998) Paronychia of the great toes in indinavir recipients. Reactions Weekly &NA;:706, 5
    CrossRef

Letters