Stefania Leuci

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.

Sleep disturbance in patients with burning mouth syndrome: a case-control study.

AIM To examine sleep complaints in patients with burning mouth syndrome (BMS) and the relationships between these disturbances, negative mood, and pain. METHODS Fifty BMS patients were compared with an equal number of healthy controls matched for age, sex, and educational level. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) were administered. Descriptive statistics, including the Mann-Whitney U test and hierarchical multiple linear regression analyses were used. RESULTS BMS patients had higher scores in all items of the PSQI and ESS than the healthy controls (P < .001). In the BMS patients, a depressed mood and anxiety correlated positively with sleep disturbances. The Pearson correlations were 0.68 for PSQI vs HAM-D (P < .001) and 0.63 for PSQI vs HAM-A (P < .001). CONCLUSION BMS patients reported a greater degree of sleep disorders, anxiety, and depression as compared with controls. Sleep disorders could influence quality of life of BMS patients and could be a possible treatment target.

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.

Clinical behaviour and long-term therapeutic response in orofacial granulomatosis patients treated with intralesional triamcinolone acetonide injections alone or in combination with topical pimecrolimus 1%

BACKGROUND Orofacial granulomatosis (OFG) is a relapsing inflammatory disorder of unknown aetiology and non-standardized treatment protocols. The aim of this study was to assess the clinical behaviour and long-term therapeutic response in OFG patients treated with intralesional triamcinolone acetonide (TA) injections alone or in combination with topical pimecrolimus 1%, as adjuvant, in those patients partially responders to TA. METHODS We analysed data from 19 OFG patients followed-up for 7 years. Demographic characteristics, clinical behaviour and long-term therapeutic response were investigated. RESULTS Eleven (57.9%) OFG patients treated with intralesional TA injections therapy reached first complete clinical remission in a mean time of 10 ± 2.2 (95% CI, 8.5-11.5) weeks, while eight (42.1%) patients, partially responders to intralesional TA injections, were treated with TA injections plus topical pimecrolimus 1%, as adjuvant, achieving complete clinical remission in a mean time of 29.8 ± 7.8 (95% CI, 23.2-36.3) weeks. Relapses occurred in four TA responder patients with a disease-free time of 35.8 ± 8.7 (95% CI, 21.9-46.4) weeks and in five patients treated with TA and topical pimecrolimus 1% with a disease-free time of 55.8 ± 18.5 (95% CI, 32.8-78.8) weeks. Patients were followed-up for a mean time of 56.3 ± 18.2 (95% CI, 47.6-65.1) months. At last control, all 19 patients were in complete clinical remission. CONCLUSION These preliminary data suggest that intralesional TA injections still represent a mainstay in the treatment of OFG. It is unclear the role of topical pimecrolimus, as adjuvant, in leading OFG patients, partly responders to intralesional TA injections, to a complete clinical remission.

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.

Multiple myeloma vs. breast cancer patients with bisphosphonates-related osteonecrosis of the jaws: a comparative analysis of response to treatment and predictors of outcome.

BACKGROUND Multiple myeloma (MM) and breast cancer (BC) are the two most common diseases associated with bisphosphonates-related osteonecrosis of the jaws (BRONJ), for which different therapeutical approaches have been proposed. The aim of this study was to compare the clinical behaviour of BRONJ in patients with MM vs. BC and the time of healing in terms of clinical and symptomatological remission, following a standardized therapeutic protocol. METHODS Twenty-six BRONJ patients (13 men with MM and 13 women with BC) were prospectively enroled and treated with a specific systemic and topical antibiotic therapy. Several predictors of outcome were also evaluated. RESULTS Nine patients (69.2%) with BC and 10 patients (76.9%) with MM progressed towards a complete clinical remission (CR) in a mean healing time of 183.3 days [SD: 113.7; 95% confidence interval (CI): 95.95-207.7] and 372.0 days (SD: 308.0; 95% CI: 151.7-592.3) (P = 0.776), respectively. The clinical improvement was statistically significant (P = 0.0013 and P = 0.0014), as well as the assessment of pain (P = 0.0015 and P = 0.0015), in MM and BC group, respectively. Cox regression analysis revealed that just triggering events (P = 0.036) were found to be significant predictors of outcome of BRONJ healing. CONCLUSIONS Both groups of cancer patients experienced clinical and symptomatological remission regardless their malignancy, but BC patients earlier than MM patients.

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-