propylthiouracil and Pyoderma-Gangrenosum

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be caused by an adverse drug reaction. We discuss the clinical presentation and outcomes of 52 cases of drug-induced PG reported to date in the literature. We conducted our literature search for case reports of drug-induced PG using keywords on PubMed and Medical Subject Heading (MeSH) terms on MEDLINE and EMBASE. To assess the probability that each case of PG was related to drug therapy, we used the Naranjo criteria. We identified 44 studies in the literature, with a total of 52 cases of drug-induced PG. The mean Naranjo score for cocaine-induced PG (n = 13) was 9.4, indicating a definite adverse drug reaction, while the mean Naranjo scores for isotretinoin (n = 5), propylthiouracil (n = 5), and sunitinib (n = 5) were 6.2, 6.8, and 7.4, respectively, indicating probable adverse drug reactions. Drugs should be considered as a possible triggering event whenever PG is diagnosed, and clinicians should particularly consider this in patients taking isotretinoin, propylthiouracil, or sunitinib, as well as in patients with a history of cocaine use.

Topics: Cocaine; Drug Eruptions; Humans; Immunosuppressive Agents; Indoles; Isotretinoin; Propylthiouracil; Pyoderma Gangrenosum; Pyrroles; Sunitinib; Tumor Necrosis Factor-alpha; Withholding Treatment

Synthetic antithyroid drugs are often used in the treatment of hyperthyroidism, regardless of aetiology. They may cause various side effects, including the development of anti-neutrophil cytoplasmic antibodies (ANCA), ANCA-associated vasculitis, and neutrophilic dermatoses. Propylthiouracil (PTU) is the antithyroid drug most frequently implicated in ANCA-associated diseases specifically involving anti-myeloperoxidase ANCA (MPO-ANCA). To our knowledge, there are no clinical reports describing the association of pyoderma gangrenosum (PG) and anti-proteinase3-ANCA (PR3-ANCA) induced by PTU, with ANCA levels decreasing after antithyroid drug withdrawal.. A 68-year-old woman was treated with propylthiouracil (PTU) for toxic multinodular goitre. She presented necrotic ulceration of the lower abdomen. The patient's history, physical examination, and bacteriological and histological samples led to a diagnosis of pyoderma gangrenosum. This pyoderma involved ANCA with antigenic specificity for proteinase 3. Withdrawal of PTU and a short course of corticosteroids and cyclosporine resulted in rapid and complete resolution of the pyoderma gangrenosum as well as a decrease in ANCA. No relapse was observed one year after cessation of treatment.. We report a case of PG associated with PR3-ANCA induced by PTU, without any demonstrable vasculitis.

Topics: Abdomen; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Biomarkers; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hyperthyroidism; Propylthiouracil; Pyoderma Gangrenosum; Treatment Outcome

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Microscopic Polyangiitis; Propylthiouracil; Pyoderma Gangrenosum; Treatment Outcome

Topics: Aged; Antithyroid Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Pyoderma Gangrenosum; Remission, Spontaneous

Topics: Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Middle Aged; Prednisolone; Propylthiouracil; Pyoderma Gangrenosum

We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far.. A 40 year-old woman was treated with propylthiouracil for Graves'disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks.. Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves'disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet's syndrome, have been described in patients with propylthiouracil-induced ANCA. One case-report described a 44 year-old woman who developed pyoderma gangrenosum associated with propylthiouracil-induced p-ANCA. These manifestations usually appear within 2 years, as our patient. The data in the literature, allows us to report the polymorphic expressions of neutrophilic dermatosis in this patient with p-ANCA which could be related to propylthiouracil. Such association of Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum with p-ANCA has never been described in this endocrinologic context so far. Furthermore we propose that neutrophilic dermatosis should be inscribed in the list of side effects induced by propylthiouracil therapy.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Antineutrophil Cytoplasmic; Antibody Formation; Antithyroid Agents; Female; Humans; Hyperthyroidism; Propylthiouracil; Pyoderma Gangrenosum; Skin Diseases, Vesiculobullous

A 27-year-old woman who had been receiving propylthiouracil for 2 years for Graves' disease presented with painful ulceration on the lower limbs which had first appeared 2 weeks previously. Well-circumscribed hemorrhagic ulcerations with ragged borders were noted on both legs. Skin biopsy demonstrated a florid neutrophilic infiltrate and evidence of leukocytoclasis around small blood vessels in the papillary dermis compatible with the diagnosis of pyoderma gangrenosum. A highly positive perinuclear pattern of antineutrophil cytoplasmic antibody with specificities for IgM myeloperoxidase was observed. The authors think that propylthiouracil is associated with the occurrence of pyoderma gangrenosum in this patient.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Diagnosis, Differential; Female; Graves Disease; Humans; Leg Ulcer; Propylthiouracil; Pyoderma Gangrenosum

The association of pyoderma gangrenosum and arthritic symptoms is well documented. We present a rarely reported variant of this in a 44-year-old woman with pyoderma gangrenosum and bilateral large purulent effusions of her knees. She had no evidence of underlying rheumatoid arthritis or a specific seronegative spondyloarthropathy. Of note she had a history of Graves' disease for which she had been treated with propylthiouracil for 3 years and on investigation at this presentation had a markedly elevated perinuclear antineutrophil cytoplasm antibody (P-ANCA) level with specificities for IgM myeloperoxidase, IgG elastase and IgG lactoferrin. We believe this patient had pyoderma gangrenosum with secondary sterile pyarthrosis and a P-ANCA precipitated by propylthiouracil.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antimetabolites; Arthritis, Reactive; Female; Graves Disease; Humans; Minocycline; Prednisolone; Propylthiouracil; Pyoderma Gangrenosum; Skin