Oral Cancer in HSCT Pediatric Patients Arising on GVHD: A Comprehensive Review.

After haematopoietic stem cell transplantation and a history of GVHD, the risk of developing secondary malignancies, including oral cancer, is higher. This risk increases with time post-transplantation; therefore, pediatric patients undergoing HSCT, who have long-term survival chances, are in a high-risk category. The aim of this review is to provide data on HSCT, GVHD, clinical manifestations, histological features and treatment of oral cancer, and outcomes in HSCT pediatric patients, affected by oral GVHD, who have been developed OSCC. Descriptive statistics were used to validate data. Fifteen studies on a total of 33 patients were selected. Data on oral cancer showed that the tongue was the most frequently involved site (13 pts; 39.39%), followed by the floor of the mouth (4 pts; 12.12%), and buccal mucosa (4 pts; 12.12%). Oral squamous cell carcinoma was the histological feature reported. There were 19 (57.58%) deaths occurring between 2 and 46.5 months after OC diagnosis. Eleven patients survived with a median follow-up of 34 months. Considering the high risk of developing oral cancer, a conventional oral examination every 6 months is recommended for HSCT pediatric patients who have developed GVHD.

Oral Dysplastic Complications after HSCT: Single Case Series of Multidisciplinary Evaluation of 80 Patients.

Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem-cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft-versus-host disease (cGVHD). The aim of this study was to describe a cohort of post-HSCT patients and to evaluate the onset of oral epithelial dysplasia and/or OSCC over time. In this retrospective cohort study, we present a cohort of hematological patients that underwent HSCT. Demographic variables, clinical hematological data, data regarding acute graft-versus-host disease (aGVHD) and cGVHD, and oral clinical features were analyzed. We focused on clinicopathological features of a subgroup of 22 patients with oral cGVHD and OSCC after HSCT. Among 80 included patients, 46 patients (57.5%) developed aGVHD and 39 patients (48.7%) developed cGVHD. Oral mucosa was involved in 17 patients with aGVHD (36.9%) and in 22 patients (56.4%) with cGVHD. Out of a total of 22 oral biopsies, roughly 40% revealed mild to moderate dysplasia, and 32% were OSCC. In the absence of international agreement on the best timing of oral follow-up after HSCT, it is mandatory to establish a close multidisciplinary evaluation in order to prevent the onset of HSCT-related OSCC and to reduce post-transplant mortality due to secondary tumors.

The use of rituximab as an adjuvant in the treatment of oral pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris patients with exclusive oral involvement (OPV) treated with conventional immunosuppressive therapy may be non-responders or experience severe side effects and/or relapses. In such cases, rituximab could be used as an adjuvant in recalcitrant OPV patients. METHODS: A retrospective single-center study on patients with oral pemphigus vulgaris treated with RTX at a dose of 375 mg/m2 was performed, evaluating the complete clinical and immunological remission, side effects of RTX, and possible correlation between anti-desmoglein (Dsg) 3 antibodies and clinical remission. RESULTS: We treated 10 OPV patients, of which 60% had a moderate and 40% mild disease severity before therapy with RTX. Complete clinical remission (CCR) was achieved in 100% of OPV patients, of which 20% developed side effects and 20% experienced a relapse in a mean time of 15.2 ± 10.2 weeks. The mean time for CCR was achieved in 19.8 ± 10.3 weeks, whereas the duration of the CCR consisted in 37.4 ± 33.5 weeks. OPV patients underwent a mean follow-up of 57.2 ± 37.7 weeks. In all patients, the mean of pemphigus disease area index (PDAI) decreased from 20.3 ± 14.1 to 0.4 ± 0.0, whereas the mean Dsg3 value dropped from 157.1 ± 40.6 to 67.0 ± 26.6 after therapy with RTX. However, no correlation was found between PDAI and anti-Dsg3 antibodies before and after therapy with RTX (P > .05). CONCLUSIONS: RTX represents a valid and safe alternative as an adjuvant in OPV patients with low rate of relapses and side effects.

Oral autoimmune vesicobullous diseases: Classification, clinical presentations, molecular mechanisms, diagnostic algorithms, and management.

Mucocutaneous blistering autoimmune diseases are a group of systemic, rare, chronic disorders characterized by humoral-mediated immunologic mechanisms against epithelial, basement membrane, and subepithelial tissues. Morbidity and mortality can be completely different among these diseases, with outcome being dependent on an early and accurate diagnosis, systemic comorbidities, and the patient's response to treatment. Definitive diagnosis is based on clinical and histopathologic findings. Because clinical presentations among these diseases are often similar, different immunofluorescence tests and ELISAs are used to confirm the specific diagnosis. Oral mucosa may often be the first site of clinical manifestation from which the disease spreads to other mucosal surfaces and skin. Thus, often dentists and oral medicine specialists may be the first to encounter patients with such diseases. In this review we discuss the most frequent autoimmune vesicobullous disorders, namely pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and linear IgA disease.

Psychological profiles in patients with symptomatic reticular forms of oral lichen planus: A prospective cohort study.

OBJECTIVES: To analyze intra, extra-oral symptoms and psychological profiles in symptomatic patients with reticular (R) forms of oral lichen planus (OLP). MATERIALS AND METHODS: Thirty symptomatic R-OLP (sR-OLP) patients were compared with an equal number of non-symptomatic R-OLP (nsR-OLP) patients, burning mouth syndrome (BMS) patients, and healthy subjects (HS). The Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI), and the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) were administered. Descriptive statistics, the non-parametric ANOVA procedure by Kruskal-Wallis, the exact Fisher test, and the multiple comparison test by the Mann-Whitney U test were performed. RESULTS: The median and IQR of the HAM-D and HAM-A were 16.0 (11.7-24.0) and 17.5 (13.7-27.2) for the BMS, 13.5 (12.0-15.0) and 15.5 (10.7-18.0) for the sR-OLP patients, 2.0 (2.0-3.2) and 2.0 (2.0-4.0) for the nsR-OLP patients, and 3.0 (2.0-4.0) and 3.0 (2.0-4.0) for the HS, respectively. The median and IQR of the NRS and T-PRI were 9.0 (7.7-10.0) and 11.0 (9.0-12.2) for the BMS and 9.0 (7.7-10.0) and 11.5 (7.0-13.0) for the sR-OLP patients, respectively. Comparison analysis between the BMS and sR-OLP patients revealed a non-significant difference between the medians of the psychological profile and pain in the two groups (P-value>.05). CONCLUSIONS: The oral complaints are correlated with anxious and depressive symptoms in sR-OLP patients. Mood disorders could modulate the pain perception or that patients could develop two different associated oral diseases, OLP and BMS.

Oral lichen planus in childhood: a case series.

BACKGROUND: Although the exact incidence of pediatric oral lichen planus (OLP) is unknown, the oral mucosa seems to be less commonly involved, and the clinical presentation is often atypical. The aim of the study is to present a case series of OLP in childhood. METHODS: From our database, we retrospectively selected and analyzed the clinical data of OLP patients under the age of 18 where the diagnosis had been confirmed by histopathological analysis. RESULTS: The case series from our database shows eight patients, four males and four females. The mean (±SD) age at the time of diagnosis of the disease was 13.5 (±2.73) years, ranging in age from 9 to 17. Clinically, a reticular pattern was present in six patients (75%), and the tongue was the most commonly involved oral site (six cases, 75%). We also report the first case of OLP in a 9-year-old girl affected by autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. CONCLUSIONS: We report the largest case series of pediatric OLP published in literature thus far. Differences in the disease between adults and pediatric patients have been detected, but further investigation and a larger case series are needed to establish any detailed differences in clinical outcomes.

Lichen planus of the lips: an intermediate disease between the skin and mucosa? Retrospective clinical study and review of the literature.

BACKGROUND: Lichen planus of the lips (LPL) is not frequently described in the literature. The objective of this study is to investigate the clinical outline, behavior, and prognosis of LPL. METHODS: Clinical data of patients with true oral lichen planus (LP) involving the lips, diagnosed and treated at our Oral Medicine Unit (University Federico II of Naples, Italy), have been collected and analyzed. Concurrently, a PubMed search was carried out from 1950 to March 2014 to assess epidemiological and clinical data about LPL. RESULTS: Our case series revealed 13 patients (female/male ratio 0.4) with a mean (± SD) age of 71.85 years (± 6.72). The lower/upper lip involvement ratio was 9, mainly with mixed clinical patterns (76.9%), generally including erosion and mild keratosis. In most cases, the lips were involved with other oral sites but displayed a better evolution of the lesions. The literature review showed 21 reports of LPL (35 patients, female/male ratio 0.4) with a mean (± SD) age of 45.35 years (± 16.19). CONCLUSIONS: In the literature, erosive (28.57%) lower lip lesions showed a clear predominance (lower/upper lip ratio 6.5). One case of malignant transformation was also reported. The prevalence of isolated LPL was clearly reported only in two studies, ranging from 0.51% to 8.9%. In our patients, lesions were mostly found at the inner border of the lower vermillion and presented a tendency for self-limitation, or to regression after treatment, like cutaneous lesions. The lip lesions were small and easy to overlook, and therefore the prevalence of these lesions may have been underestimated.

The Relationship Between Sociodemographic Characteristics and Clinical Features in Burning Mouth Syndrome.

OBJECTIVE: To compare sociodemographic and clinical characteristics in patients with burning mouth syndrome (BMS) and their relationship with pain. DESIGN: Cross-sectional clinical study. SETTING: University-Hospital. SUBJECTS: 75 BMS patients were enrolled. METHODS: The study was conducted between September 2011 and March 2012 at the "Federico II" University of Naples. Demographic characteristics and clinical information including age, sex, educational level, marital status, job status, age at disease onset, oral symptoms, and triggers were collected via questionnaire interviews. To assess pain intensity the visual analogue scale (VAS) was administered. Descriptive statistics were collected, and Pearson Chi-square tests, Kruskal-Wallis nonparametric tests and the Spearman bivariate correlation were performed. RESULTS: The mean age was 61.17 (±11.75, female/male ratio = 3:1). The mean age at disease onset was 56.75 (±12.01). A low educational level (8.57 ± 4.95) and 80% of unemployment were found. Job status and age at disease onset correlated with the VAS scale (P = 0.019 and P = 0.015, respectively). Tongue morphology changes, taste disturbances, and intraoral foreign body sensation have a significant dependence on gender (P = 0.049, 0.001, and 0.045, respectively); intraoral foreign body sensation has a significant dependence on marital status (P = 0.033); taste disturbances have a significant dependence on job status. (P = 0.049); xerostomia has a significant dependence on age (P = 0.039); and tongue color changes and a bitter taste have a significant dependence on educational level (P = 0.040 and 0.022, respectively). Marital status and educational level have a significant dependence on the triggers (P = 0.036 and 0.049, respectively). CONCLUSIONS: The prevalence of BMS is higher in women, and in married, unemployed, and less highly educated patients. Burning is the most frequent symptom while stressful life events are the most frequent trigger reported.

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.

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.

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.

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.

Unexplained somatic comorbidities in patients with burning mouth syndrome: a controlled clinical study.

AIMS: To evaluate the prevalence of unexplained extraoral symptoms in a group of patients with burning mouth syndrome (BMS) and compare the prevalence with that in patients with oral lichen planus (OLP) and age- and gender-matched controls. METHODS: The occurrence of extraoral symptoms was analyzed in a group of 124 BMS patients, a group of 112 oral lichen planus (OLP) patients, and a group of 102 healthy patients. Oral symptoms were collected by a specialist in oral medicine and a general dentist, while data concerning unexplained extraoral symptoms were gathered by each specialist ward, ie, ophthalmology, gynecology, otolaryngology, gastroenterology, neurology, cardiology, internal medicine, and dermatology. A Fisher exact test (α = .05) and Kruskal-Wallis test (α = .05) were performed for statistical analysis. RESULTS: In the BMS group, 98 (96.1%) patients reported unexplained extraoral symptoms, while 4 (3.9%) patients reported only oral symptoms. A painful symptomatology in different bodily regions was reported more frequently by BMS patients (83.3%) than by OLP patients (1.8%) and healthy patients (11.7%) (P < .0001). The differences in the overall unexplained extraoral symptoms between BMS (96.1%) and OLP patients (9.3%) (P < .0001) and between BMS (96.1%) and healthy patients (15.7%) (P < .0001) were statistically significant. The unexplained extraoral symptoms in BMS patients consisted of pain perceived in different bodily areas (odds ratio [OR]: 255; 95% confidence interval [CI]: 58.4-1112), ear-nose-throat symptoms (OR: 399.7; 95%CI: 89.2-1790), neurological symptoms (OR: 393; 95% CI: 23.8-6481), ophthalmological symptoms (OR: 232.3; 95% CI: 14.1-3823), gastrointestinal complaints (OR: 111.2; 95% CI: 42.2-293), skin/gland complaints (OR: 63.5; 95% CI: 3.8-1055), urogenital complaints (OR: 35; 95% CI: 12-101), and cardiopulmonary symptoms (OR: 19; 95% CI: 4.5-82). CONCLUSION: The great majority of BMS patients presented with several additional unexplained extraoral comorbidities, indicating that various medical disciplines should be involved in the BMS diagnostic process. Furthermore, the results suggest that BMS may be classified as a complex somatoform disorder rather than a neuropathic pain entity.

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.

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

BACKGROUND: 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.

Nikolsky's sign on the gingival mucosa: a clinical tool for oral health practitioners.

BACKGROUND: Nikolsky's sign is a clinical sign which is elicited by a horizontal, tangential pressure to the mucosa and/or skin resulting in blisters extending and separating or peeling away. Few data are currently available in the literature about its usefulness, specificity, and sensitivity in the diagnosis of either oropharyngeal or cutaneous bullous diseases. The purpose of this study was to determine the sensitivity and specificity of the gingival Nikolsky's sign in the identification of an autoimmune blistering disease. METHODS: Over a period of 13 years, we recruited 566 patients with autoimmune oral bullous and non-bullous diseases who possessed either maxillary or mandibular gingival mucosal lesions. All patients were subjected to a test causing a gingival Nikolsky's sign at their first visit during the diagnostic algorithm and in the active disease phase before commencing treatment. RESULTS: A total of 566 patients (184 with and 382 without bullous lesions) had at least gingival involvement. A positive gingival Nikolsky's sign resulted in 100 (17.7%) of 566 patients: 86 patients with bullous lesions (53 with pemphigus vulgaris, eight with mucous membrane pemphigoid, 22 with bullous/mixed lichenoid lesions, and three with erythema multiforme) and 14 with non-bullous lesions (12 with non-bullous lichenoid lesions and two with systemic lupus erythematous/mixed connective tissue disease). Thus, the specificity of Nikolsky's sign was higher (96.3%) than the sensitivity (46.7%). CONCLUSION: The results of this study support the use of Nikolsky's sign of the gingival mucosa as a viable test to establish the presence of oral bullous diseases.

Adjuvant high-dose intravenous immunoglobulin therapy can be easily and safely introduced as an alternative treatment in patients with severe pemphigus vulgaris: a retrospective preliminary study.

BACKGROUND: Long-term corticosteroid therapy, often in association with other immunosuppressive agents, is considered the mainstay of pemphigus vulgaris (PV) therapy. Recent evidence has been changing this paradigm as patients who are non-responsive to conventional therapies or who experience severe adverse effects have been successfully treated with high-dose intravenous immunoglobulin (IVIg). However, the shift from conventional therapies to IVIg represents a major challenge in the daily practice of non-experienced clinicians because of potential adverse effects and other issues relevant to IVIg therapy such as the necessity for premedication, selection of cases, modality of infusion, patient monitoring, and the cost and length of hospital stay. OBJECTIVE: The purpose of this preliminary study was to evaluate and report outcomes of treatment with IVIg in eight selected PV patients meeting clearly defined criteria for initiation of this therapy. METHODS: Available guidelines for IVIg therapy in patients with autoimmune mucocutaneous blistering diseases were followed. Clinical response, induction and duration of remission, strategies for prevention of adverse effects, and total days of hospital stay in eight patients with severe PV treated with IVIg were retrospectively evaluated. RESULTS: All patients had an effective clinical response without adverse reactions, leading to a significant corticosteroid-sparing effect. CONCLUSION: Our results indicate that, when current guidelines are followed, IVIg therapy can be easily and safely introduced as a treatment alternative in patients with severe PV. Careful monitoring of patients, utilization of a multidisciplinary approach, and evaluation of hospital-related issues can help the non-experienced clinician successfully manage patients with severe PV requiring IVIg therapy.

Variations in serum hemoglobin, albumin, and electrolytes in patients receiving intravenous immunoglobulin therapy: a real clinical threat?

BACKGROUND AND OBJECTIVE: Intravenous immunoglobulin (IVIg) is a solution of globulins containing antibodies derived from pooled human plasma of donors and used in the treatment of a number of immune deficiencies and autoimmune diseases. However, several investigators have reported biochemical alterations with use of IVIg. The objective of this study was to evaluate the effects of IVIg therapy on selected biochemical and hematologic parameters in patients with autoimmune mucocutaneous blistering diseases (AMBDs). METHODS: In this preliminary clinical study, ten patients with AMBDs (seven with pemphigus vulgaris and three with mucous membrane pemphigoid) received 133 cycles of IVIg for a total of 399 infusions. We evaluated the effects of IVIg therapy on serum hemoglobin (Hb), albumin, and electrolyte levels, including sodium (Na+), potassium (K+), chloride (Cl-) and calcium (Ca2+). Values of these parameters were measured 24 hours before, during, and 24 hours and 4 weeks after the 3-day infusion period. RESULTS: The observed variations in serum electrolyte levels were physiologically and clinically negligible. Furthermore, 24 hours after the last infusion, mean electrolyte values had spontaneously returned to normal levels without the need for additional supplementation: Na+ 137.59+/-1.42 mmol/L (p=0.6091 vs baseline); K+ 3.97+/-0.5 mmol/L (p=0.2689); Cl- 103.4+/-2.69 mmol/L (p=0.0388); and Ca2+ 9.07+/-0.44 mg/dL (p=0.5332). Conversely, significant variations in mean Hb and albumin levels were observed. When measured 24 hours after the last infusion, mild/moderate decreases in Hb (11.62+/-2.12 g/dL; p=0.009 vs baseline) and/or albumin (mean 3.14+/-0.24 g/dL; p=0.0016 vs baseline) were evident. Such changes may, albeit very rarely, be of sufficient clinical significance in individual patients as to necessitate additional treatment. CONCLUSION: In patients receiving intravenous IVIg for AMBDs, electrolyte values should be monitored but do not represent a real clinical threat. Hemoglobin and albumin values may be altered sufficiently to require additional treatment but this is a very rare occurrence. These findings confirm and extend previous reports of the safety of IVIg therapy.

High-dose intravenous 'pulse' methylprednisone in the treatment of severe oropharyngeal pemphigus: a pilot study.

BACKGROUND: High-dose intravenous (i.v.) methylprednisolone has been used therapeutically in severe blistering diseases to avoid the complications and side-effects of long-term orally administered glucocorticoid therapy. The aim of the study is to evaluate the capacity of methylprednisolone i.v. 'pulse' therapy to induce remission in the treatment of severe oropharyngeal pemphigus. METHODS: Twelve patients, all of whom had oropharyngeal severe pemphigus, were included in the analysis. There were eight women and four men whose ages ranged from 22 to 78 years (mean age: 50.75 years) with a disease duration of 1-3 months(mean duration: 55 days). In order to obtain a rapid clinical remission of extensive mucosal lesions, we performed 'pulse' therapy with intravenous methylprednisolone (30 mg/kg body weight to a maximum of 1 g per dose on each of 3-5 consecutive days)evaluating the clinical response and the short-term side-effects. RESULTS: Our therapy was generally safe and well tolerated with a very low rate of side-effects. All patients responded to i.v. methyl-prednisolone with evidence of a decrease in signs and symptoms within l week of commencing treatment and in all cases remission was observed after the second or the third cycle of 'pulse'. The most common adverse events during treatment were flushing and hyperglycaemia; in a few cases we observed a metallic taste in the mouth, pruritus, headaches ranging from mild to moderate, palpitations, mood alterations, insomnia and fatigue. CONCLUSIONS: High-dose 'pulse' administration of glucocorticoids is a potentially effective therapy to be considered in the treatment of patients with severe oropharyngeal pemphigus. Similar patients treated with conventional oral administered doses of prednisone or deflazacort had protracted courses requiring months of glucocorticoid therapy with no long-term remissions. However, further well-designed, long-term comparative trials are required to confirm this.