Skip to main content
eScholarship
Open Access Publications from the University of California

Pentoxifylline: A drug with wide spectrum applications in dermatology

  • Author(s): Zargari, Omid
  • et al.
Main Content

Pentoxifylline: A drug with wide spectrum applications in dermatology
Omid Zargari MD, FAAD
Dermatology Online Journal 14 (11): 2

Pars Clinic, Rasht, Iran. ozargari@iranderma.com

Abstract

Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug Administration for the treatment of intermittent claudication, but studies have shown that it has a variety of physiological effects at the cellular level, which may be important in treating a diverse group of diseases.


Clinical applications of PTX in dermatology have been reviewed by Samlaska et al [1]. More recent clinical indications in dermatology will be discussed following a brief review of its effects at cellular levels.


Effects of PTX on different cellules and molecules


Anti-TNF-α effects

Tumor Necrosis Factor-α (TNF-α) is a cytokine with a wide spectrum of activity which is predominantly produced by mononuclear cells. Increasing evidence has implicated TNF-α as a pivotal molecule involved in the pathogenensis of a wide variety of acute and chronic inflammatory disease states including many skin diseases such as psoriasis, graft-versus-host-disease (GVHD), contact dermatitis and leprosy reactions.

Several studies have revealed that PTX is an active inhibitor of TNF-α [2, 3]. Therefore, it could be considered as a therapeutic option in TNF-α mediated skin diseases.


Hemorheologic effects

Pentoxifylline affects almost all factors responsible for blood viscosity (Table 1) and is indeed the first known hemorheologically active drug [4]. The primary hemorheological effects of PTX are caused by increased red blood cell deformability and decreased blood viscosity. The mechanism by which this is achieved has been shown to involve increased erythrocyte adenosine triphosphate (ATP) and other cyclic nucleotide levels [5].

Hemorheological properties of PTX are not completely confined to its effects on red blood cells; by increasing intracellular cAMP levels, PTX leads to the inhibition of thromboxane synthesis and an increase of prostacyclin synthesis. Therefore, platelet aggregation and adhesion to vessel walls is also inhibited. In addition, it increases tissue plasminogen activator and plasmin and this complex of effects makes PTX a valuable drug for improving hypercoagulable states. Interestingly, PTX causes platelet disaggregation only in conditions in which the platelets are hyperaggregable, but does not cause prolonged bleeding or any platelet abnormalities in normal persons [4, 6].

Furthermore, PTX increases leucocyte deformability and regarding this new concept that polymorphonuclear leukocytes may play even a greater role in whole blood viscosity [7, 8], it can be considered as an almost complete rheologic drug.


Antifibinolytic effects

Pentoxifylline increases fibroblast collagenases and decreases collagen, fibronectin and glycosaminoglycan production [9]. Although, these effects could be due to anti TNF-α properties of PTX, studies have revealed that this inhibitory activities of PTX on fibroblasts are mediated by a separate mechanism [10].


Other effects

Pentoxifylline is a non-selective inhibitor of cyclic-3', 5'-phosphodiesterase (PDE), which leads to a broad-spectrum effects against cell proliferation and inflammation.

Pentoxifylline is an inhibitor of production of IL-1 and IL-6, an inhibitor of T and B cell activation, and a suppressor of neutrophil degranulation. Furthermore, it has been shown that it reduces the expression of adhesion molecules such as ICAM-1, on keratinocytes and E-selectin expression on endothelial cells [11].


Pharmacokinetics, Dosage and Side Effects

Pentoxifylline is readily absorbed from the gastrointestinal tract and its peak plasma level is achieved within 2 hours, but it undergoes first-pass hepatic metabolism [12, 13, 14]. The usual adult dosage of PTX is 400 mg TID with meals. However, in patients with renal insufficiency the dose has to be adjusted.

Overall, PTX is a very safe drug and is usually well tolerated. Its most common side effects are those of the gastrointestinal tract and central nervous system which appear in approximately 3 percent of patients [14]. The main central nervous system side effects are dizziness, headache, anxiety, and confusion. These side effects are dose-related and can be minimized by reduction of the dose.


Clinical applications in Dermatology


Peripheral vascular diseases

Several studies have shown that PTX therapy produces subjective and objective improvements in a significant percentage of patients with peripheral vascular disease and also improves walking distance by 18-59 percent in these patients [15, 16]. Indeed the main indication of PTX is for the treatment of intermittent claudication; it has been marketed in Europe since 1972 for this purpose.


Venous leg ulcers

Recent histological and immunocytochemical analyses of venous leg ulcers suggest that inflammatory reactions play a great role in these ulcers. These inflammatory reactions lead to fibrosclerotic remodeling of the skin and then to ulceration. The leukocyte activation is accompanied by the expression of integrins and by synthesis and release of many inflammatory molecules, including proteolytic enzymes, leukotrienes, prostaglandin, bradykinin, free oxygen radicals, cytokines, and possibly other classes of inflammatory mediators [17]. As leukocytes become activated, they become rigid and immobile; this leads to further occlusion of small vessels and trophic changes in the overlying skin [8]. With this in mind, the attention of many investigators has been drawn to use PTX as an adjunctive therapy in venous leg ulcers. Results of a prospective randomized, controlled study on 80 eligible patients with confirmed venous ulcers have shown complete healing in 57.5 percent of patients receiving PTX in comparison with 27.5 percent of patients in the control group (p=0.013). This study has concluded that PTX is an efficacious medication in the treatment of venous ulcers in patients unable to tolerate compression therapy [18]. A systematic review has also shown that PTX with compression is more effective than placebo with compression in patients with venous leg ulcers [19].


Vasculopathies and vasculitides

Due to its multiple effects on various blood cell types and probably through its anti-inflammatory effects, PTX could be a useful drug in treating vasculopathies. Indeed, several studies have shown the beneficial effects of PTX in idiopathic livedoid vasculopathies and some authors suggest it as a drug of choice for this condition [20, 21, 22].

Cutaneous vasculitides are usually managed primarily with colchicine, dapsone, and prednisone. Theoretically, PTX can act as a sparing agent in different kinds of vasculitides, both through its extensive hemorheologic effects and also by neutralizing proinflammatory cytokines. Specifically, it seems that PTX works synergistically with dapsone in treating hypocomplementemic urticarial vasculitis [23, 24].


Pigmented purpuric eruptions

Although there is limited evidence, one study of three cases of Schamberg's disease revealed showed successful treatment with PTX. The authors suggested that PTX acts through its effects on adhesion molecules in this disease [11].


Psoriasis

Perhaps the prototype of TNF-α mediated diseases in dermatology is psoriasis. Indeed, some of the new biologic drugs for psoriasis act by inhibition of this cytokine. The beneficial effects of PTX in psoriasis have been shown in nude mice in both in vivo and in vitro studies [25], but there is a lack of sufficient studies in humans.

Pentoxifylline can be used also as an adjuvant therapy in psoriasis. In at least two situations, its beneficial effects in psoriasis have been reported; it has been suggested that PTX counteracts many of the unwanted effects of cyclosporine on red blood cells, platelets and coagulation factors [4, 26]. One study has shown that PTX ameliorates cyclosporine nephrotoxicity in humans [27]. In addition, abnormal metabolism of triglyceride is not an uncommon finding in psoriatic patients [28, 29] and may be also exaggerated after cyclosporine therapy [30]. Because a possible beneficial of PTX is in reducing serum triglycerides, it seems that a combination of PTX and cyclosporine is a very sensible choice. Randomized, clinical trials are needed to compare both the clinical response and lipid profiles in psoriatic patients on cyclosporine with or without adjuvant PTX.

Furthermore, there is also some evidence that concomitant PTX therapy may reduce the incidence and severity of gastrointestinal complaints and flushing in patients receiving fumaric acid esters [31], a widely used anti-psoriatic drug in northern Europe.


Leprosy

An increase in TNF-α has been implicated in type II leprosy reaction.

Several studies have been documented that PTX rapidly ameliorates the systemic symptoms of type II leprosy reaction and could be an ideal alternative for thalidomide [32, 33, 34].

In a study, serum TNF-α was assayed before and during treatment with PTX in 15 patients with erythema nodosum leprosum (ENL). The increased TNF-α levels recorded in the circulation during the reaction were dramatically reduced within three to seven days of the initiation of therapy. In vitro TNF-α production was assayed upon mononuclear cell culture stimulation with Mycobacterium leprae. A reduction of inducible TNF-α in peripheral blood mononuclear cells was seen after one to two weeks of in vivo administration of PTX. These data suggest that PTX inhibits TNF-α production in ENL patients both in vivo and in vitro; thus it may be useful in the treatment of this type of leprosy reaction [34].


Leishmaniasis

Tumor Necrosis Factor-α has been also implicated in the immunopathogenesis of cutaneous leishmaniasis. It is expressed in lesions of patients with American cutaneous leishmaniasis and has been shown to be elevated in the serum of patients with mucocutaneous leishmaniasis [35].

Several studies have shown that PTX, as an adjuvant to pentavalent antimonials could be regarded as an effective tool in treating both mucosal and cutaneous leishmaniasis [35, 36, 37].

Also, a very recent study has shown that PTX can prevent renal functional alterations induced by meglumine antimonate in rats [38]. Therefore, it seems that PTX is an ideal adjuvant in treating patients with leishmaniasis.


Sarcoidosis

Although a specific inciting antigen has not yet been identified for sarcoidosis, it appears to be a Th1-mediated disease; TNF-α likely plays a critical role in granuloma formation in this disease [39].

Pentoxifylline can almost completely inhibit spontaneous TNF-α production from alveolar macrophages of sarcoidosis patients [40]. Clinically, in an open-label trial, Zabel et al. have documented that PTX is an effective drug in the treatment of pulmonary sarcoidosis [41], but specific studies addressing the treatment of cutaneous sarcoidosis have yet to be done.


Aphthosis and Behcet disease

There are some reports that have shown the efficacy of PTX in treating recurrent oral and genital aphthosis [42, 43, 44]. Furthermore, PTX has been used by many rheumatologists for the treatment of Behcet disease (BD). PTX reduces the severity and duration of the symptoms [45, 46]. Although these beneficial effects may be due to the anti-TNF-α properties of PTX, a recent study has shown that erythrocyte deformability is decreased in active BD patients in comparison with healthy control subjects. Hence, the therapeutic mechanism underlying the beneficial effect of PTX in BD is possibly the correction of impaired erythrocyte deformability [47]. PTX can be also regarded as a preventive modality for thrombotic events, which are among the other characteristics of BD.


AIDS

Increased levels of TNF-α have been demonstrated in many patients with AIDS [48]; Pentoxifylline has been shown to decrease TNF-α expression, serum fasting triglycerides, and HIV replication in these patients [49]. Also, it has been documented that PTX is a safe and efficacious treatment for the pruritic papular eruption of HIV/AIDS, a common and usually recalcitrant manifestation of HIV infection [50].


Graft-versus-host disease (GVHD)

Cytotoxic T-lymphocyte -mediated tissue injury and inflammatory cytokines including TNF-α play important roles in the pathogenesis of GVHD. Therefore, theoretically PTX could be a useful drug in reducing the incidence of this disease. However, the existent studies concerning the prophylactic efficacy of PTX in GVHD are quite conflicting [51].


Miscellaneous (Kasabach-Merritt syndrome, pretibial myxedema, burn and radiation fibrosis)

One child achieved a significant increase in platelet count with PTX, which was utilized with good results between age 15 months to 5 years of age [52].

Theoretically, through its antifibfinolytic activities, PTX could be useful in treating fibroblast-mediated diseases such as pretibial myxedema. Pineda et al. have demonstrated that 2 months of therapy with PTX in combination with topical glucocorticoids resulted in reduction of thickness of skin lesions in a 48-year-old woman with pretibial myxedema; after 4 months, complete resolution of the lesions was observed. Interestingly her ophthalmopathy was also improved [53]. Engin and his colleagues have reported another case of pretibial myxedema which was succesfully treated with a combination of PTX and intralesional triamcinolone acetonide [54].

A recent study suggests that Pentoxifylline has a direct effect on inhibiting burn scar fibroblasts. Perhaps, PTX will be a valuable drug for reducing burn scar contractures in the future [55].

The treatment of 34 radiation-induced superficial fibrotic lesions with pentoxifylline and vitamin E for 3 months revealed a significant effect of the Pentoxifylline-vitamin E combination in improving radiation-induced fibrosis [56].


Conclusion

In conclusion, it seems that PTX is able to help dermatologists in a wide spectrum of skin diseases (Table 2). However, the paucity of the clinical trials makes it difficult to draw definite conclusions about the degree of benefit of PTX in various clinical settings.

When using PTX therapy it should be kept in mind that in most cutaneous diseases the beneficial effects may not be evident until after several weeks or even months of treatment. For some diseases the full improvement may take several years. Some reports of treatment failure may be due to an inadequate therapy duration [57, 58].

Furthermore, it should be stressed that in most conditions PTX should be regarded as a valuable therapeutic adjuvant rather than a primary treatment. Specifically, PTX may best serve as a corticosteroid-sparing agent in skin diseases.

References

1. Samlaska CP, Winfield EA. Pentoxifylline. J Am Acad Dermatol 1994;30:603-21 PubMed

2. van Furth AM, Verhard-Seijmonsbergen EM. Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-alpha, IL-1 beta IL-10 by human leucocytes. Immunology 1997;91:193-6 PubMed

3. Strieter RM, Remick DG, Ward PA, Spengler RN, Lynch JP, Larrick J, et al. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun. 1988;155:1230-1236 PubMed

4. Ely H. Pentoxifylline therapy in dermatology: a review of localized hyperviscosity and its effect on the skin. Dermatol Clin 1988;6:585-608 PubMed

5. Porsche E, Stefanovich V. The influence of pentoxifylline on ATPase activity of human erythrocyte membranes. IRCS J Med Sci 1978;6:285

6. Ely H. Is pentoxifylline the drug of the decade? J Am Acad Dermatol 1994;30:639-42 PubMed

7. Nees S, Schonharting M. On the role of different blood cell types in the rheological behavior of whole blood. Clin Hemorheol 1987;7:417

8. Ely H. White blood cells as mediators of hyperviscosity-induced tissue damage in neutrophilic vascular reactions: therapy with pentoxifylline. J Am Acad Dermatol 1989;20:677-80 PubMed

9. Berman B, Duncan MR. Pentoxifylline inhibits normal human dermal fibroblast in vitro proliferation, collagen, glycosaminoglycan, and fibronectin production, and increases collagenase activity. J Invest Dermatol 1989;92:605-10 PubMed

10. Berman B, Wietzerbin J, Sanceau J, Merlin G, Duncan MR. Pentoxifylline inhibits certain constitutive and tumor necrosis factor-α induced activities of human normal dermal fibroblasts. J Invest Dermatol 1992;98;706-12 PubMed

11. Kano Y, Hirayama K, Orihara M, Shiohara T. Successful treatment of Schamberg's disease with pentoxifylline. J Am Acad Dermatol 1997; 36: 827-30 PubMed

12. Smith RV, Waller ES, Doluisio JT, Bauza MT, Puri SK, Ho I, Lassman HB. Pharmacokinetics of orally administered pentoxifylline in humans. J Pharm Sci 1986;75:47-52 PubMed

13. Dettelbach HR, Aviado DM. Clinical pharmacology of pentoxifylline with special reference to its hemorrheologic effect for the treatment of intermittent caludication. J Clin Pharmacol 1985;25:8-26 PubMed

14. Ward A, Clissold SP. Pentoxifylline: a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 1987; 34:50-97 PubMed

15. Strano A, Davi G, Avellone G, Novo S, Pinto A. Double blind, crossover study of the clinical efficacy and the hemorheological effects of pentoxifylline in patients with occlusive arterial disease of the lower limbs. Angiology 1984; 35: 459-66 PubMed

16. Porter JM, Cutler BS, Lee BY, Reich T, Reichle FA, Scogin JT, Strandness DE. Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. Am Heart J 1982; 104: 66-72 PubMed

17. Pascarella L, Schonbein GW, Bergen JJ. Microcirculation and venous ulcers: a review. Ann Vasc Surg 2005; 19:921-7 PubMed

18. Nikolovska S, Pavlova L, Petrova N, Gocev G, Ivanovski M. Pentoxifylline--efficient in the treatment of venous ulcers in the absence of compression? Acta Dermatovenereol Croat 2002; 10:9-13 PubMed

19. Jull A, Waters J, Arroll B. Pentoxifylline for treatment of venous leg ulcers: a systematic review. Lancet 2002 4; 359:1550-4 PubMed

20. Sams WM. Livedo vasculitis: therapy with pentoxifylline. Arch Dermatol 1988;124:684-7 PubMed

21. Marzano AV, Vanotti M, Alessi E. Widespread livedoid vasculopathy. Acta Derm Venereol 2003; 83:457-60 PubMed

22. Ely H, Bard JW. Therapy of livedo vasculitis with pentoxifylline. Cutis 1988;42:448-53 PubMed

23. Nurnberg W, Grabbe J, Czarnetzki BM. Urticarial vasculitis syndrome effectively treated with dapsone and pentoxifylline. Acta Derm Venereol 1995; 75:54-6 PubMed

24. Nurnberg W, Grabbe J, Czarnetzki BM. Synergistic effects of pentoxifylline and dapsone in leucocytoclastic vasculitis. Lancet 1994;343:491 PubMed

25. Gilhar A, Grossman N, Kahanovicz S, Reuveni H, Cohen S, Eitan A. Antiproliferative effect of pentoxifylline on psoriatic and normal epidermis. In vitro and in vivo studies. Acta Derm Venereol 1996 ;76:437-41 PubMed

26. Ely H. Recent developments in dermatologic uses of cyclosporine and amelioration of renal toxicity with pentoxifylline. Curr Opin Dermatol 1993;223-30

27. Anand S, Krishna G, Grossman R, Kapoor S, Goldfarb S. Pentoxifylline ameliorates cyclosporine (CsA) nephrotoxicity in humans. J Am Soc Nephrol 1992;3:719

28. Pfahl F, Rouffy J, Duperrat B, Puissant A. Hyperlipoproteinemias in psoriasis. Ann Dermatol Syphiligr (Paris) 1976; 103:15-22 PubMed

29. Campalani E, Allen MH, Fairhurst D, Young HS, Mendonca CO, Burden AD, et al. Apolipoprotein E gene polymorphisms are associated with psoriasis but do not determine disease response to acitretin. Br J Dermatol 2006; 154:345-52 PubMed

30. Grossman RM, Delaney RJ, Brinton EA, Carter DM, Gottlieb AB. Hypertriglyceridemia in patients with psoriasis treated with cyclosporine. J Am Acad Dermatol 1991; 25:648-51 PubMed

31. Friedrich M, Sterry W, Klein A, Ruckert R, Docke WD, Asadullah K. Addition of pentoxifylline could reduce the side effects of fumaric acid esters in the treatment of psoriasis. Acta Derm Venereol (Stockh) 2001; 81: 429-30 PubMed

32. Welsh O, Gomez M, Mancias C, Ibarra-Leal S, Millikan LE. A new therapeutic approach to type II leprosy reaction. Int J Dermatol 1999; 38:931-3 PubMed

33. Nery JA, Perisse AR, Sales AM, Vieira LM, Souza RV, Sampaio EP, Sarno EN.

The use of pentoxifylline in the treatment of type 2 reactional episodes in leprosy. Indian J Lepr 2000; 72: 457-67 PubMed

34. Sampaio EP, Moraes MO, Nery JA, Santos AR, Matos HC, Sarno EN. Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-α) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). Clin Exp Immunol 1998;111: 300-8 PubMed

35. Báfica A, Oliveira F, Freitas LA, Nascimento EG, Barral A. American cutaneous leishmaniasis unresponsive to antimonial drugs: successful treatment using combination of N-methilglucamine antimoniate plus pentoxifylline. Int J Dermatol. 2003; 42:203-7 PubMed

36. Sadeghian G, Nilforoushzadeh MA. Effect of combination therapy with systemic glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis. Int J Dermatol. 2006 ;45:819-21 PubMed

37. Machado PR, Lessa H, Lessa M, Guimarães LH, Bang H, Ho JL, et al. Oral pentoxifylline combined with pentavalent antimony: a randomized trial for mucosal leishmaniasis. Clin Infect Dis. 2007;44:788-93 PubMed

38. Moura FJ, Leal PP, Furtado Rde S, Muniz-Junqueira MI, Veiga JP. Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride. Toxicology. 2008 14;243(1-2):66-74 PubMed

39. Moller DR. Involvement of T-cells and alterations in T-cell receptors in sarcoidosis. Semin Respir Infect 1998;13:174-83 PubMed

40. Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U. Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. Am J Respir Crit Care Med. 1999;159:508-11 PubMed

41. Zabel P, Entzian P, Dalhoff K, Schlaak M. Pentoxifylline in treatment of sarcoidosis. Am J Respir Crit Care Med. 1997;155:1665-9 PubMed

42. Pizarro A, Herranz P, Ferrer M, Casado M. Recurrent oral aphthosis: treatment with pentoxifylline. Med Clin (Barc). 1993; 101:237 PubMed

43. Pizarro A, Herranz P, Garcia-Tobaruelaa A, Casado M. Pentoxifylline in the treatment of orogenital aphthosis and Behcet's syndrome. Med Clin (Barc). 2000; 115:678 PubMed

44. Thornhill MH, Baccaglini L, Theaker E, Pemberton MN. A randomized, double-blind, placebo-controlled trial of pentoxifylline for the treatment of recurrent aphthous stomatitis. Arch Dermatol 2007;143:463-70 PubMed

45. Yasui K, Ohta K, Kobayashi M, Aizawa T, Komiyama A. Successful treatment of Behcet disease with pentoxifylline. Ann Intern Med. 1996; 124:891-3 PubMed

46. Liang GC, Chang EM. Pentoxifylline use for Behcet's Disease. Adv Exp Med Biol 2003;528: 591-4 PubMed

47. Uskudar O, Erdem A, Demiroglu H, Dikmenoglu N. Decreased erythrocyte deformability in Behcet's disease. Clin Hemorheol Microcirc 2005; 33:89-94 PubMed

48. Lahdevirta J, Maury CPJ, Teppo A-M, Repo H. Elevated levels of circulating cachectin tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med. 1988; 85:289-291 PubMed

49. Dezube BJ, Pardee AB, Chapman B, Beckett LA, Korvick JA, Novick WJ, et al. Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. J Acquir Immun Defic Syndr. 1993;6:787-794 PubMed

50. Berman B, Flores F, Burke G. Efficacy of pentoxifylline in the treatment of pruritic papular eruption of HIV-infected persons. J Am Acad Dermatol 1998; 38: 955-9 PubMed

51. Clift RA, Bianco JA, Appelbaum FR, Buckner CD, Singer JW, Bakke L, et al. A randomized controlled trial of pentoxifylline for the prevention of regimen-related toxicities in patients undergoing allogeneic marrow transplantation. Blood 1993 1;82:2025-30 PubMed

52. de la Hunt MN. Kasabach-Merritt syndrome: dangers of interferon and successful treatment with pentoxifylline. J Pediatr Surg 2006; 41:e29-31 PubMed

53. Pineda AM, Tianco EA, Tan JB, Casintahan FA, Beloso MB. Oral pentoxifylline and topical clobetasol propionate ointment in the treatment of pretibial myxoedema, with concomitant improvement of Graves' ophthalmopathy. J Eur Acad Dermatol Venereol. 2007;21(10):1441-3 PubMed

54. Engin B, Gümüşel M, Ozdemir M, Cakir M. Successful combined pentoxifylline and intralesional triamcinolone acetonide treatment of severe pretibial myxedema. Dermatol Online J. 2007; 1;13(2):16 PubMed

55. Rawlins JM, Lam WL, Karoo RO, Naylor IL, Sharpe DT. Pentoxifylline inhibits mature burn scar fibroblasts in culture. Burns 2006; 32:42-5 PubMed

56. Haddad P, Kalaghchi B, Amouzegar-Hashemi F. Pentoxifylline and vitamin E combination for superficial radiation-induced fibrosis: a phase II clinical trial. Radiother Oncol 2005; 77:324-6 PubMed

57. Cohen KL, Lucibello FE, Chomiak M. Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. Diabetes Care 1990;13:1074-7 PubMed

58. Lee SS, Ang P, Tan SH. Clinical profile and treatment outcome of livedoid vasculitis: a case series. Ann Acad Med Singapore 2003; 32:835-9 PubMed

© 2008 Dermatology Online Journal