Giulio Fortuna

Mucormycosis in immunocompetent patients: a case-series of patients with maxillary sinus involvement and a critical review of the literature.

OBJECTIVES To review the current literature on mucormycosis in immunocompentent/otherwise healthy individuals, to which five new cases with maxillary sinus involvement have been added. METHODS We searched in the PudMed database all articles in the English language related to human infections caused by fungi of the order Mucorales, in immunocompetent/otherwise healthy patients, starting from January 1978 to June 2009. In addition, we updated the literature by reporting five new cases diagnosed and treated at the oral medicine unit of our institution. RESULTS The literature review showed at least 126 articles published from 35 different countries in the world, to a total of 212 patients described. The most affected country was India with 94 (44.3%) patients and the most representative clinical form was the cutaneous/subcutaneous with 90 (42.5%) patients. Our five immunocompetent patients with a diagnosed infection of Mucorales localized at the maxillary sinus completely healed with lyposomial amphotericin B. CONCLUSIONS The literature analysis revealed that even in immunocompetent/otherwise healthy individuals mucormycosis infection has a worldwide distribution. What might be the real predisposing factors involved in its pathogenesis in such patients and the real causes of this peculiar geographic distribution still remains unknown. It is likely that, in our cases, a chronic insult of a well-defined and localized body area might have resulted in a local immunocompromission, thus fostering the development of an invasive fungal infection.

Adjuvant triamcinolone acetonide injections in oro-pharyngeal pemphigus vulgaris

Background  High‐potency topical and perilesional/intralesional corticosteroids are becoming increasingly useful as adjuvant to treat autoimmune blistering diseases.

Oropharyngeal pemphigus vulgaris and clinical remission: a long-term, longitudinal study.

AbstractBackground: The pattern of clinical remission in pemphigus vulgaris patients still remains a controversial issue because of the limited data reported in the literature. Objective: To evaluate the time to clinical remission in patients with exclusive oropharyngeal pemphigus vulgaris. Methods: We conducted a long-term, longitudinal study in a university hospital. We treated 37 patients with oropharyngeal pemphigus vulgaris, who underwent a periodic follow-up for an average of 5.3 years, and evaluated their outcome in terms of clinical remission. The main outcome measure was the clinical outcome (assessed by objective measures of severity, extent of disease, intensity of therapy, and remission) before and after conventional immunosuppressive therapy. Results: Complete and long-lasting clinical remission was achieved in 35 patients (94.6%) with oropharyngeal lesions, of whom 13 (35.1%) were off therapy and 21 (56.8%) were on therapy at the last evaluation. One patient (2.7%) died following a stroke 3 years after complete remission on therapy. Partial remission was achieved in two patients (5.4%). The mean time to achieve complete clinical remission was 4.7 ± 2.57 months after commencement of therapy. In all patients the mean disease severity score decreased from 7.81 ± 1.35 at time of diagnosis to 1.0 ± 0.9 at time of clinical remission (p < 0.0001 vs baseline), while the extent of the disease decreased from 2.9 ± 1.0 to 0.27 ± 0.45 (p < 0.0019 vs baseline) and the intensity of therapy from 4.91 ± 0.64 to 0.70 ± 0.57 (p < 0.0001 vs baseline). The mean duration of complete remission was 63.53 ± 44.9 months. Conclusions: In almost all patients with oropharyngeal pemphigus vulgaris it was possible to schedule a safe tapering of the conventional immunosuppressive therapy very shortly after the disease was controlled. Thus, we may conclude that: (i) the percentage of patients with oropharyngeal pemphigus vulgaris who achieved complete long-lasting clinical remission was very high; (ii) transient lesions that healed within a week were very frequent and had to be actively controlled; (iii) if treated early, most patients had a good clinical response and could achieve a disease- and drug-free clinical remission; (iv) early treatment may prevent extension or progression of disease; (v) there is a possible role for immunosuppressive agents; and (vi) a more favorable course of the disease, in terms of attainment and duration of clinical remission and a better prognosis, seemed to be related to a rapid response to therapy rather than to the initial severity and extent of the disease.

Analysis of thromboembolic risk related to high-dose intravenous immunoglobulin treatment: a preliminary clinical study of 10 patients with autoimmune mucocutaneous blistering diseases

Background.  Intravenous immunoglobulin (IVIg) treatment is a well‐known treatment that has been used successfully in a broad spectrum of autoimmune diseases. Currently no data are available in the literature about the role of IVIg in the pathogenesis of thromboembolic events in patients with autoimmune blistering diseases refractory to conventional immunosuppressive treatment.

Lichen planus pemphigoides, a possible example of epitope spreading

Oral lichen planus and mucous membrane pemphigoid are 2 autoimmune chronic inflammatory diseases with different clinical features. Their pathogenesis is also different, with oral lichen planus characterized by a cellular autoimmune response (lymphocytic-mediated) and mucous membrane pemphigoid determined by immunoglobulin-mediated humoral autoimmune activity. We report the cases of 2 female patients who, after an initial diagnosis of oral lichen planus, developed mucous membrane pemphigoid in a period ranging from 3 to 11 years. Both of these disorders were diagnosed via clinical, histologic, and immunologic parameters. They were refractory to conventional immunosuppressive therapy but responsive to intravenous immunoglobulin therapy. Further investigations are necessary to better elucidate whether and how a progressive development from one unrelated immunologic disorder to another may occur. Data provided herein allows us to hypothesize that epitope spreading phenomenon might be the underlying mechanism.

Oral Crohn's Disease: A Favorable Clinical Response With Delayed-Release Triamcinolone Acetonide Intralesional Injections

Oral Crohns Disease: A Favorable Clinical Response With Delayed-Release Triamcinolone Acetonide Intralesional Injections

Sunitinib Adverse Event: Oral Bullous and Lichenoid Mucositis

TO THE EDITOR: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (c-Kit), and colony-stimulating factor-1 receptor.1 It was approved for the treatment of renal and gastrointestinal stromal tumors2 and recently showed antitumor activity in patients with metastatic breast cancer.1 This case is the first to describe the oral clinical aspects of sunitinib-suspected oral mucositis toxicity in a patient with breast cancer. Case Report: A 57-year-old female with a history of metastatic breast cancer, left mastectomy, and homolateral axillary lymphoadenectomy received an anthracycline-based chemotherapy regimen (fluorouracil/epirubicin/cyclophosphamide) and then exemestane (25 mg orally once daily); this was replaced by fulvestrant (250 mg intramuscularly monthly) because of low tolerability. Due to the progression of metastatic disease, she received sunitinib malate cycles (25 mg orally 3 times per day) for a 14 day-cycle, with 7 days off and, concurrently, zolendronic acid (4 mg intravenously monthly) and omeprazole (20 mg orally twice daily). During the first and second cycles, the patient developed mild face and palmoplantar rash with edema that disappeared spontaneously within 24 hours. Dechallenge and rechallenge procedures were performed to allow a third cycle at a lower sunitinib dosage (25 mg twice daily), but during the second day, she developed persistent and painful bullous mucositis localized on the right ventral surface and edge of the tongue (Figure 1a), as well as lichenoid and necrotizing areas on the hard palate (Figure 1b), which appeared 12 hours after the second day of the third cycle. The Nikolsky’s sign, performed on both sites, was positive. Extraoral examination revealed the presence of severe palmoplantar desquamation, with a diffuse facial and axillary rash and edema. The patient refused rechallenge. Histopathological and immunological essays from oral and skin biopsies allowed us to exclude a drug-induced autoimmune mucocutaneous blistering disease, such as pemphigus vulgaris. Use of the Naranjo probability scale indicated a probable relationship between sunitinib and hand-foot skin syndrome and oral mucositis.3 No other adverse effects or hematological abnormalities, except for mild lymphopenia, were detected. Discussion: Although the frequency of grade 3/4 toxicities occurring with sunitinib is relatively low (<10%) and is most often reported in renal cell cancer rather than metastatic breast cancer studies, the oral adverse event, always described as stomatitis or mucositis, nonetheless occurred with varying frequency (10–30%).4 Our case is unique because, for the first time, it describes the clinical aspects of sunitinib-induced stomatitis, characterized by bullous and erosive lesions with widespread lichenoid and necrotizing areas. The patient discontinued sunitinib and received prednisone (25 mg once daily) for 3 days and topical corticosteroids for 7 days. She was counseled to modify her diet, eat soft foods, avoid alcohol, and maintain meticulous oral hygiene by using a toothbrush with soft bristles and a diluted solution of chlorhexidine 0.12%. Ten days later she was in complete clinical remission. The first target of sunitinib is the capillary endothelium, which blocks VEGFR 1/2/3, PDGFR, c-KIT, and FMS-like tyrosine kinase 3. However, the presence of these receptors has also been detected in other tissues, for example, c-KIT in the acini and ducts of salivary glands,5 in human keratinocytes,6 and VEGFR-1 in the epidermal layer of unwounded skin.7 It is likely that the initial damage induced by sunitinib in the oral cavity may affect not only vascular tissue, but also salivary glands and keratinocytes. Once the damage is established, these lesions might selfmaintain, due to an impairment of wound-healing mechanisms. Indeed, the wound repair mechanisms are regulated via VEGF, which is ex-

Secondary syphilis mimicking pemphigus vulgaris

© 2008 The Authors JEADV 2009, 23, 441–496 Journal compilation

Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis

Sirs:Capecitabine is an oral prodrug that is converted to onlyone active metabolite, fluorouracil (5-FU), which is used totreat numerous types of neoplasms, such as those of thebreast, esophagus, and larynx cancer, as well as metastaticbreast cancer as either a single agent or in combination withdocetaxel after the failure of prior anthracycline-basedchemotherapy [ 1]. The Federal Drug Administration hasrecently approved the combination of capecitabine andlapatinib for the treatment of advanced or metastatic breastcancer overexpressing human epidermal growth factorreceptor-2 [ 2].We treated a 61-year-old female patient with breastcancer who, following a right mastectomy, homolateralaxillary lymphoadenectomy, and radiotherapy, entered intoremission. After 7 years of remission, metastatic progres-sion of the disease was determined, and the patient receivedradiotherapy and anthracycline-based chemotherapy, whichwere only partially successful. A drug regimen of lapatinib[1250 mg daily oral dose (PO qd)] continuously pluscapecitabine (2000 mg/m

Metastatic prostate cancer presenting as paraneoplastic pemphigus: a favourable clinical response to combined androgen blockade and conventional immunosuppressive therapy

1 Smith FJ, Jonkman MF, van Goor H et al. A mutation in human keratin K6b produces a phenocopy of the K17 disorder pachyonychia congenita type 2. Hum Mol Genet 1998; 7:1143–8. 2 Terrinoni A, Smith FJ, Didona B et al. Novel and recurrent mutations in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia congenita. J Invest Dermatol 2001; 117:1391–6. 3 McLean WH, Smith FJ, Cassidy AJ. Insights into genotype–phenotype correlation in pachyonychia congenita from the human intermediate filament mutation database. J Investig Dermatol Symp Proc 2005; 10:31–6. 4 Leachman SA, Kaspar RL, Fleckman P et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10:3–17. 5 McLean WH, Rugg EL, Lunny DP et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 1995; 9:273–8. 6 Smith FJ, Liao H, Cassidy AJ et al. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10:21–30. 7 Wu JW, Xiao SX, Liu Y et al. Identification of two recurrent mutations in keratin genes in three cases with pachyonychia congenita. J Eur Acad Dermatol Venereol 2008 Apr 22 [Epub ahead of print].