Excess granulation tissue responses associated with isotretinoin therapy

Multiple polypoid projections of granulation tissue developed in two patients receiving isotretinoin for acne. Histological study of the lesions revealed increased amounts of non-sulphated acid mucopolysaccharides in the ground substance of the granulation tissue stroma. Complete resolution occurred following curettage with or without chemical cautery. The role of isotretinoin in the development of these lesions is discussed.     

Eruptive milia during isotretinoin therapy

Isotretinoin (13‐cis‐retinoic acid) is a synthetic vitamin A derivative that is effective in the treatment of recalcitrant, nodulocystic acne. To our knowledge, there are no reports in the medical literature of milia as a side effect of isotretinoin. We report a case of eruptive facial milia in the setting of isotretinoin treatment for acne.     

Herpetic whitlow during isotretinoin therapy

Isotretinoin is an extremely valuable drug that is occasionally associated with well-known mucocutaneous side-effects, including cheilitis, retinoid dermatitis, palmoplantar desquamation, and photosensitivity. Paronychia has been reported rarely: only two prior cases of herpes simplex infections associated with isotretinoin have been previously reported. We present the first known case of herpetic paronychia occurring in an atopic patient while on isotretinoin therapy for acne.     

Pyogenic granuloma-like acne lesions during isotretinoin therapy

Three male patients with severe nodulocystic acne were treated with oral isotretinoin in a dosage of 0.5 to 1.0 mg/kg/day. A flare of their disease developed, characterized by an inflammatory, hemorrhagic, pyogenic, granuloma-like response of previously crusted acne lesions. This reaction occurred between the sixth and ninth weeks of treatment and was confined entirely to the chest and back. The severity of the reaction prompted the administration of oral prednisone and, in two cases, the discontinuation of isotretinoin therapy. In one patient, pyoderma gangrenosum developed on the thigh. The exact incidence of this pyogenic, granuloma-like reaction to isotretinoin is unknown, although we have seen it in three of 66 patients with nodulocystic acne treated with this drug. The cause of the reaction is unknown, but it may be due to the increased skin fragility and vascular proliferation known to be induced by isotretinoin.     

Retinoid therapy is associated with excess granulation tissue responses

In our clinical trials of isotretinoin therapy for cystic acne and etretinate treatment of psoriasis, eight patients had growth of excessive granulation tissue. The granulation tissue was found in resolving acne lesions in one patient taking isotretinoin. Among the psoriatic patients taking etretinate, the granulation tissue usually was seen adjacent to nail plates. In two patients, the side effect caused them to stop retinoid therapy. The tissue response did not appear to be related to the daily or cumulative retinoid dose.     

Beta-adrenoceptor blockade delays granulation tissue formation in polyurethane sponge implants

Background:  The role of adrenoceptors in granulation tissue formation is not well understood. The aim of this study was to investigate the effects of alpha- and beta-adrenoceptor blockade on granulation tissue development using polyurethane (PU) implants in the rat.
Methods:  Animals were treated orally with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist) or phentolamine (alpha1- and alpha2-antagonist) until euthanasia. The control group received only water. All animals received subcutaneous implants of PU sponges. After 14 days, implants were collected, formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin and eosin and Sirius red and immunostained for CD68 and alpha-smooth muscle actin.
Results:  The number of inflammatory cells and the volume density of myofibroblasts and blood vessels were lower in the control group than in the propranolol- and atenolol-treated groups. The collagen fiber score was greater in the control group than in the propranolol- and atenolol-treated groups. The inflammatory infiltrate, collagen fiber score, blood vessel density or myofibroblast differentiation was not affected by phentolamine. The percentage of fibrovascular invasion was greater in the antagonist-treated groups than in the control group.
Conclusions:  Blockade of beta1- and beta2-adrenoceptors, but not alpha-adrenoceptors, impairs granulation tissue development in PU implants due to interference with the inflammatory response.     

Acne fulminans and erythema nodosum during isotretinoin therapy responding to dapsone

Acne vulgaris is very common, 85% of teenagers being affected at any one time. In most cases, the disease is mild and patients do not present to the dermatologist. Most are instead treated with over-the-counter products and conventional treatment such as peeling agents or topical and systemic antibiotics. Isotretinoin has revolutionized the treatment of severe acne unresponsive to oral antibiotics. Explosive and very severe acne such as pyoderma faciale, acne conglobata and acne fulminans are rare, the features that distinguish acne fulminans from the other conditions being systemic upset with fever, joint pain, malaise and leucocytosis,^1–3 while there have been two reports of the condition associated with erythema nodosum.^4,5 The recommended treatment for acne fulminans is a combination of oral steroids and systemic antibiotics, isotretinoin probably not being the treatment of choice.⁶ We now report a patient who developed acne fulminans and erythema nodosum within 3 weeks of starting isotretinoin and then responded to dapsone without oral steroids.     

Uses and complications of isotretinoin therapy

Isotretinoin (13-cis-retinoic acid) is a retinoid that has been used over the past 2 decades to treat a wide variety of dermatologic conditions, some with great success. Although it is beneficial in many skin conditions, the side effects and toxicities of oral retinoids require careful monitoring by experienced physicians. The clinical applications of oral retinoids continue to expand both within and beyond the field of dermatology.