Association between human leukocyte antigens and cutaneous adverse drug reactions to antiepileptics and antibiotics in the Iranian population.

In this case-control study, class І and ІІ human leukocyte antigen (HLA) alleles in Iranian patients with benign and severe cutaneous adverse drug reactions (CADRs) due to aromatic anticonvulsants and antibiotics were evaluated. Patients diagnosed with CADRs (based on clinical and laboratory findings) with a Naranjo score of ≥ 4 underwent blood sampling and HLA-DNA typing. The control group comprised 90 healthy Iranian adults. Alleles with a frequency of more than two were reported. Deviations from Hardy-Weinberg equilibrium were not observed. Eighty patients with CADRs including 54 females and 26 males with a mean age of 41.49 ± 16.08 years were enrolled in this study. The culprit drugs included anticonvulsants (lamotrigine, carbamazepine, and phenytoin) and antibiotics (ciprofloxacin and co-trimoxazole). The comparison of allele frequencies in the Iranian healthy control group and the group with benign CADRs revealed that HLA-Cw*04, and HLA-A*24 were significantly associated with lamotrigine-induced maculopapular CADRs. Furthermore, HLA-B*51 showed a significant correlation with carbamazepine-induced maculopapular CADRs. Significant associations were also detected between ciprofloxacin-induced urticarial CADRs with HLA-B*40, and HLA-DRB1*14. In the severe group, HLA-B*38 and HLA-DRB1*13 were significantly associated with lamotrigine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Moreover, HLA-A*31 and HLA-Cw*04 were significantly correlated with carbamazepine-induced drug reactions with eosinophilia and systemic symptoms (DRESS). HLA-B*08 also showed a significant correlation with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP). In conclusion, Lamotrigine-induced MPE was significantly correlated with HLA-Cw*04, and HLA-A*24. Similarly, lamotrigine-induced SJS/TEN was significantly associated with HLA-B*38 and HLA-DRB1*13. Additionally, HLA-A*31 was associated with DRESS caused by carbamazepine. The most frequent CADR-inducing drugs were anticonvulsants.

Punctate Pattern and Pemphigus: Is There Any Evidence of Punctate Pattern Among Iranian Patients?

AIM: To examine the prevalence of this novel pattern among Iranian patients with pemphigus and peruse the relationship between the presence of a punctate pattern with clinical severity of disease and histopathological findings. METHODS: One hundred recently diagnosed patients with pemphigus were enrolled. DIF evaluation and routine light microscopy were performed on their biopsy specimens. Disease severity was determined using the Pemphigus Disease Area Index. Serum samples were collected to measure autoantibody titers using enzyme-linked immunosorbent assay. RESULTS: All the samples evaluated by DIF showed a continuous linear pattern of intercellular IgG deposition, whereas none of them had a punctate pattern. Despite a significant correlation between the Pemphigus Disease Area Index score and autoantibody values, no association between histopathological findings and disease severity has been found. CONCLUSION: We could not detect any punctate pattern among Iranian patients with pemphigus. The importance of this pattern in the diagnosis of pemphigus might be different among patients with different ethnic and genetic factors.

Decreased serum levels of interleukin-17, interleukin-23, TGF-ß in pemphigus vulgaris patients, and their association with disease phase.

The exact pathogenesis of Pemphigus Vulgaris (PV) has remained unclear, but it seems that cytokines play critical roles in this disease. This study aims to assess the serum levels of interleukin (IL)-6, IL-17, IL-23, and TGF-ß in PV patients and compare the results to the healthy controls. Serum levels of IL6, IL-17, IL-23, and TGF-ß were successfully determined by enzyme-linked immunosorbent assay (ELISA) in 27 newly diagnosed PV, 32 patients in remission, and 29 healthy controls. It was shown that the mean serum levels of IL-17, IL-23, and TGF-ß serum are significantly different among the PV patients and healthy controls (P values: <.001, .001, and .003, respectively). It was found that new PV patients have lower serum levels of IL-17, IL-23, and TGF-ß as compared to healthy controls (P values: <.001, <.001, and .003, respectively). Regarding IL-6, no significant difference was observed between the healthy controls and the other two groups of patients. IL-17, IL-23, and TGF-ß are involved in the pathogenesis of PV. However, more studies are required to clarify their exact roles in the immunopathogenesis of PV.

C4d immunohistochemical stain of formalin-fixed paraffin-embedded tissue as a sensitive method in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common type of subepidermal bullous disease. Direct immunofluorescence (DIF) is the gold standard for diagnosis, but it requires a fresh tissue specimen. This study was conducted to evaluate the accuracy of using immunohistochemical (IHC) analysis for the detection of C4d in paraffin-embedded tissue of BP cases. METHODS: A retrospective study was performed on 30 BP cases (confirmed by Hematoxylin and eosin [H&E] and DIF) and 30 controls. IHC studies were performed on formalin-fixed paraffin-embedded (FFPE) tissues. RESULTS: Of 30 BP patients (11 male and 19 female), 27 (90%) were C4d positive and three patients (10%) were C4d negative. The C4d deposits were seen as linear brown stain along the dermoepidermal junction (18 cases), around basal keratinocytes (eight cases), or Civatte-like (three cases). Two cases revealed more than one pattern in IHC staining. Of 30 control specimens, 26 (86%) cases were C4d negative and four (13.4%) were positive for granular deposits of C4d which were diagnosed as dermatitis herpetiformis. CONCLUSION: C4d IHC study is a valuable diagnostic tool with sensitivity of 90% and specificity of 86.7%, and is especially useful in cases in which frozen specimens are not available or FFPE specimens are the only available material for analysis.

Efficacy of Folic Acid and Vitamin B12 Replacement Therapies in the Reduction of Adverse Effects of Isotretinoin: A Randomized Controlled Trial.

Previous studies have reported elevated homocysteine levels and folic acid and/or vitamin B12 deficiencies after isotretinoin therapy, which increase the risk of cardiovascular and neuropsychiatric disorders. Homocysteine is metabolized in the liver, a process requiring folate and vitamin B12. We conducted a randomized controlled trial to investigate whether folate and vitamin B12 replacement therapy with isotretinoin would be useful for preventing hyperhomocysteinemia. A total of 66 patients with acne were randomized into two groups: group A took isotretinoin, folic acid, and vitamin B12, whereas group B took isotretinoin alone. Treatment was continued for 2 months. Blood homocysteine, folic acid, and vitamin B12 levels were measured before and after treatment. In group A, a significant decrease in homocysteine level was observed after treatment (P=.0004), although it was still within the normal range. Folic acid and vitamin B12 levels significantly increased (P=.0026 and P=.0002, respectively). In group B, no significant changes were observed in the levels of homocysteine and vitamin B12, but folic acid levels decreased significantly (P=.02). We concluded that folic acid and vitamin B12 supplementation during isotretinoin therapy could be useful for preventing folate deficiency and improving blood homocysteine levels; this might as a result reduce the risks for cardiovascular and neuropsychiatric disorders in patients taking isotretinoin.

Occurrence of Mycosis Fungoides in an Iranian Chemical Victim of the Iran-Iraq War with a Long-term Follow-Up: A Case Report and Review of Literature.

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Persistent antigenic stimulation has been claimed to play a role in the development of this malignancy. We aimed to show the role of sulfur mustard in the pathogenesis of MF. A 45-year-old man with MF is introduced herein. He was a victim of chemical exposure in 1987 during the Iran-Iraq war. He developed skin lesions 3 years after exposure to sulfur mustard gas at the age of 21. Seven years after his exposure to sulfur mustard gas, a biopsy from the posterior distal part of his calf, which was injured and had bulla, revealed MF. Later, he developed more lesions on his extremities, trunk, and abdomen. On his previous admission, his left eyebrow was involved. A punch biopsy specimen was obtained from his eyebrow lesion, which rendered diffuse infiltration of atypical lymphocyte cells with some convoluted nuclei and scant cytoplasm admixed with lymphocytes, histiocytes, and mast cells compatible with the nodular stage of MF. At his last admission, a biopsy was obtained from the plaque lesions on his left thigh, and a TCR-γ gene rearrangement of the paraffin block of the plaque lesions revealed positive monoclonality. All the findings supported the MF diagnosis. We concluded that sulfur mustard could be a risk factor for MF development.

Patch testing in Iranian children with allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis is a common disorder in adults and children alike and appears to be on the increase. The purpose of this study was to determine the sensitization trends in Iranian children with contact dermatitis. METHODS: The result of 109 patch tests performed using the 24 allergens of the European Standard Series in patients below 18 years old from September 2007 to March 2009 were recorded and analyzed. The tests were evaluated at 48 and 72 h after performing. RESULTS: The study population consisted of 72 (66.1 %) females and 37 (33.9 %) males. Hands were the most commonly affected anatomic site. In the final evaluation of the tests on day three, 51 (46.8 %) individuals showed a positive reaction to at least one allergen. Females were significantly more likely to show a positive response to at least one allergen (p-value = 0.031, odds ratio: 2.46). The most common allergens were nickel sulfate, cobalt, methylisothiazolinone, and colophony with 21 (19.3 %), 11 (10.1 %), 7 (6.4 %), and 6 (5.5 %) positive reactions, respectively. Contact allergy to nickel sulfate was more common in females than males (23.6 % vs. 10.8 %). There was no statistically significant relationship between personal or family history of atopy and a positive reaction to patch testing. The clinical and practical relevance were assessed for nickel and cobalt with a clinical current relevance in 11 (52.3 %) and 4 (36.4 %), respectively. CONCLUSIONS: Nickel sulfate, cobalt, methylisothiazolinone, and colophony are the most common allergens responsible for induction of allergic contact dermatitis in Iranian children and adolescents. Females tended to show more positive reactions to allergens.

Hydroa vacciniforme with eye involvement: report of two cases.

We herein report two patients with hydroa vacciniforme and concomitant ophthalmic involvement, primarily in the form of keratoconjunctivitis leading to corneal opacity. Awareness of this occasional manifestation may help to prevent severe complications.

Serologic Biomarkers in Pemphigus Monitoring: C-reactive Protein, Macrophage Migration Inhibitory Factor, and Prolactin Levels Versus Autoantibody Assays.

Evaluation and monitoring of pemphigus vulgaris (PV) typically involve autoantibody detection by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF). We aimed to determine the levels of antipemphigus immunoglobulin (Ig) G autoantibodies using ELISA and IIF (as standard biomarkers), and compare it to prolactin, macrophage migration inhibitory factor (MIF), and C-reactive protein (CRP) (as nonstandard biomarkers) to determine which of these non-standard biomarkers is appropriate for PV monitoring. The experiment was performed before and during therapy. Anti-Dsg immunoglobulin G autoantibodies were measured using ELISA and IIF (as standard biomarkers) versus prolactin, MIF, and CRP (nonstandard), before 1 and 3 months after the treatment. Before beginning the treatment, the severity of the disease was determined using the pemphigus disease area Index (PDAI). We enrolled 60 newly diagnosed patients with PV (32 men and 28 women; mean age=43.8±14.2 years). Before treatment, the levels of anti-Dsg1, anti-Dsg3, and IIF were high and had a significant relationship with PDAI. PDAI also had a connection with the levels of CRP and prolactin. The anti-Dsg1, anti-Dsg3, IIF, and CRP titers decreased in patients treated with conventional (prednisolone plus azathioprine) and rituximab therapy during and after treatment. In conclusion, anti-Dsg1, anti-Dsg3, and IIF autoantibody titers remain standard biomarkers for assessing disease activity, severity, and PV monitoring. The trend of CRP was similar to that of anti-Dsg1, anti-Dsg3, and IIF. Thus, CRP may be used for PV monitoring.

An analysis of 101 primary cosmetic rhinoplasties.

PURPOSE: Primary cosmetic rhinoplasty is one of the most complex of cosmetic surgical procedures in the maxillofacial area that requires precise consideration to both form and function. The complex and variable anatomy, highly visible position of the nose, and distinct patient desires contribute to the complexity of this procedure. This study reports the combined results of 101 consecutive primary cosmetic rhinoplasties at 2 centers. PATIENTS AND METHODS: A retrospective chart review was completed on all patients who had primary cosmetic rhinoplasty with or without septoplasty and who were operated on by the senior authors (S.C.B. and H.M.) from June 2006 through December 2008. A standard physical examination, including photo documentation, was completed on each patient preoperatively. All patients were followed periodically after surgery for at least 12 months. Outcome was measured by both subjective and objective measures of cosmetic and functional (breathing) outcome. The following data were collected and analyzed: age of patient, gender, chief cosmetic and functional complaint, details of surgical procedure (including septoplasty, grafts, and donor sites), complications, and report of subjective outcome at final evaluation. RESULTS: One hundred one patients (n = 101, average age 24.4 ± 6.8 years old) were enrolled in the study. Most patients presented for consultation regarding cosmetic rhinoplasty (80%) versus septorhinoplasty (20%). Although most of the patients (63%) were treated with septorhinoplasty, the open rhinoplasty (transcollumellar) incision was used in 61% of patients versus the closed rhinoplasty (39%) technique. The most commonly performed combination of techniques used was the combination of nasal tip modification, with dorsal reduction and nasal osetotomies (54%), followed by tip modification with dorsal reduction (19%), and dorsal reduction with osteotomies (18%) and no tip modification. In the 50 patients who required a graft, in 80% the donor site was the nasal septum. Spreader grafts were used in 14% of patients, and a combination of shield/tip graft was used in 52%. The following complications were observed: unhappy patient 16%, dehiscence at incision 5%, asymmetry requiring revision 6%, and infection 1%. In the 63 patients that had septoplasty, 6 (9.5%) reported that their breathing was not improved. In this series 11 patients (11%) received a revision rhinoplasty. CONCLUSIONS: Primary cosmetic rhinoplasty is 1 of the more complex facial cosmetic procedures. The vast majority of complications can be avoided with careful and extensive treatment planning. In this series we found a complication and revision rate similar to that reported in the literature.

The Dopamine Gene Receptors (DRD1-5) Expression Alteration in Psoriasis Patients.

BACKGROUND: Psoriasis is a chronic inflammatory autoimmune disease that is considered linked to genetic and environmental factors such as stress. Since the neurotransmitter dopamine has a close association with stress configuration, it can be a candidate for relieving psoriasis representation. In addition to the CNS, immune cells can play a decisive role in regulating immune functions through dopamine synthesis and the expression of its receptors. Altered response of immune cells to dopamine as well as a distorted expression of dopamine receptors (DRs) in immune cells have been reported in some chronic inflammatory conditions. OBJECTIVE: This study aims the evaluation of dopamine receptor (DR1-DR5) gene expression in mononuclear blood cells of psoriatic patients in comparison with normal individuals. METHODS: We isolated peripheral mononuclear cells (PBMCs) from blood samples followed by total RNA extraction, cDNA synthesis, and real-time PCR using specific primer pairs. RESULTS: We found that all types of DRs are expressed in the PBMCs of normal and psoriatic individuals. We also concluded that compared to controls, DR2 and DR4 were overexpressed in psoriasis patients while DR3 was low-expressed. CONCLUSION: Increased expression of DR2 and DR4 along with decreased expression of DR3 in PBMCs of psoriasis patients not only provide new insight into the pathogenesis of psoriasis but may also be effective in designing future therapeutic strategies attributable to psoriasis.

Pilot study of safety and efficacy of topical liposomal amphotericin B for cutaneous leishmaniasis caused by Leishmania major in Islamic Republic of Iran.

Background: Topical nanoliposomes containing 0.4% amphotericin B (Lip-AmB 0.4%) have shown promising safety results in preclinical and phase 1 clinical trials in healthy volunteers. Aims: To evaluate safety and efficacy of Lip-AmB 0.4% in cutaneous leishmaniasis patients. Methods: Fourteen patients with a total of 84 lesions received national standard treatment of weekly intralesional meglumine antimoniate with biweekly cryotherapy, or daily intramuscular meglumine antimoniate (20 mg/kg/day for 14 days), and topical Lip-AmB 0.4% twice daily for 28 days. Twenty-two patients with a total of 46 lesions (7 at most) were treated with topical Lip-AmB 0.4% alone twice daily for 28 days. Thirty patients with a total of 68 lesions received national standard treatment of weekly intralesional meglumine antimoniate (to blanch around the lesion) and biweekly cryotherapy. Results: Sixty-six patients with cutaneous leishmaniasis lesions completed the study. In the safety evaluation, 2 of the 36 patients evaluated reported a tolerable burning sensation and they preferred to continue treatment. Twelve (92%) of 14 patients with 84 lesions who received national standard treatment combined with Lip-AmB 0.4% completed the study with complete cure. In 1 of the patients with 4 lesions, 1 lesion showed complete cure and 3 showed partial cure. Among 22 patients with 46 lesions who received only topical LipAmB 0.4%, 19 completed the study and 18 showed complete cure (95% efficacy). In the 30 patients who received national standard treatment alone, 33 lesions in 15 patients showed complete cure (48.5%) on day 42 follow-up. Conclusion: Lip-AmB 0.4% alone or in combination with national standard treatment is safe with high-efficacy rate and warrants further investigation during phase 3 clinical trials.

A single blind randomized clinical study: the efficacy of isotretinoin plus narrow band ultraviolet B in the treatment of psoriasis vulgaris.

In this randomized clinical trial, 39 patients with psoriasis vulgaris were randomized in two groups. Intervention group received narrow band ultraviolet B (NBUVB)+isotretinoin (0.5 mg/kg/day), control group received NBUVB+placebo. Psoriasis Area Severity Index (PASI) scoring was recorded at baseline and weeks 4, 10, and 14. Thirty-seven patients completed the study. According to recorded PASI scores the difference between efficacies of two treatments was not significant. Complete clearing was noticed in 14 and 13 patients in intervention group and controls. The mean cumulative NBUVB dose in intervention group and controls was 29.95 ± 16.11 vs. 45.77 ± 7.72J/cm(2) (P=0.004). Isotretinoin+NBUVB can reduce number of phototherapy sessions and cumulative NBUVB dose.

Decreased Serum Levels of Interleukin-4 and Interleukin-21 in New Pemphigus Vulgaris Patients, but Not Chronic Patients With Inactive Disease Compared to Healthy Controls.

BACKGROUND: Pemphigus is a rare group of autoimmune blistering diseases with unknown etiology and unclear pathogenesis. Pemphigus vulgaris (PV) is the most common subtype, and is characterized by ulcerations or flaccid blisters on mucous membranes and on the skin. It is accepted that cytokines have a critical role in the pathogenesis of PV, while their exact roles remain to be elucidated. OBJECTIVES: This study assessed serum levels of interleukin (IL)-4 and IL-21 in different phases of the disease in comparison with healthy controls. METHODS: In a case-control cohort design, serum levels of IL-4 and IL-21 were determined by ELISA in three groups: patients with newly diagnosed PV, patients with chronic, inactive PV (PV in remission), and healthy controls. RESULTS: The study included 88 individuals (58 women and 30 men), including 26 with newly diagnosed PV, 33 with PV in remission, and 29 healthy controls. A significant difference was found among the groups for IL-21 (P = .044), but not for IL-4 (P = .374). Serum levels of IL-4 and IL-21 in newly diagnosed patients were significantly lower than in healthy controls (P = .005 for both), but these cytokine levels in patients with PV in remission were not different from those of controls (P = .343 and P = .221, respectively). Also, no differences in cytokine levels were detected between the newly diagnosed patients and patients with PV in remission. Regardless of disease phase, we detected significantly lower levels of IL-21 in patients than controls (P = .027), but no differences for IL-4 (P = .374). CONCLUSIONS: IL-4 and IL-21 are involved in PV pathogenesis and disease severity. More studies are required to clarify the role of IL-4 and IL-21 in immunopathogenesis and immune response during PV.

Old world cutaneous leishmaniasis in Iran: clinical variants and treatments.

BACKGROUND: Old World cutaneous leishmaniasis (OWCL) is endemic in Iran and most cases of cutaneous leishmaniasis (CL) are caused by Leishmania major, and then Leishmania tropica, and rarely by Leishmania infantum. OBJECTIVE: We aimed to describe clinical variants of OWCL and their treatments. METHOD: Through literature search in PubMed, Scopus and Embase and google scholar, we have found articles about variant clinical pictures of OWCL and their treatments. RESULTS: The following clinical variants of OWCL namely; localized forms, zosteriform, erysipeloid, eczematoid, warty, localized Leishmania lymphadenitis, sporotrichoid, hyperkeratotic, impetiginized, mucosal involvement in CL, lupoid leishmaniasis, chronic lesions due to leishmanization, disseminated cutaneous leishmaniasis, reactivation of CL after transplantation and coexistence of CL with other diseases, are reported from Iran. The mainstay of therapy remains pentavalent antimonial compounds and cryotherapy is an adjuvant to therapy. Treatment with antifungal agents, miltefosine, amphotericin B and herbal extract such as ZH-E have also been used. Treatment of CL in chronic cases and in immunosuppressed patients is difficult and relapse may occur. CONCLUSION: In clinical variants of CL with long duration and multiple lesions, systemic pentavalent antimonial compounds are first step of therapy. In case of incomplete response or resistant to classic treatment, combination therapy is indicated.

Serum Levels of Interleukin 18 and Interleukin 10 in Iranian Patients with Bullous Pemphigoid and Their Correlation with BP180-NC16a and BP230.

No Abstract.

Immune response in cutaneous leishmaniasis patients with healing vs. non-healing lesions.

BACKGROUND AND OBJECTIVES: The outcome of Leishmania infection mainly depends upon the Leishmania species which causes the disease and the generation of the type of host immune response, the healing process and protection in leishmaniasis depends upon induction of Th1 response. In this study, the Th1/Th2 cytokine profile in cutaneous leishmaniasis (CL) is evaluated. MATERIALS AND METHODS: This study was carried out in leishmaniasis clinic of CRTSDL, TUMS, during March 2018 to March 2019. Peripheral blood mononuclear cells (PBMC) of volunteers with active healing and non-healing lesion (s) of cutaneous leishmaniasis (CL), volunteers with and without history of CL were cultured and stimulated with Soluble Leishmania antigen (SLA). The supernatants were collected and the levels of IFN-γ, IL-5 and IL-10 were titrated using ELISA method. RESULTS: The results showed a significantly higher levels of IFN-γ in volunteers with active CL healing form (p<0.005), history of CL (p<0.005) than healthy volunteers. A significantly (p<0.005) higher level of IFN-γ was seen in volunteers with active healing form of lesion than non-healing form. There was a significantly (p<0.005) higher level of IL-10 in volunteers with a history of non-healing form and active non-healing form of CL. There was no significant difference in IL-5 production in PBMC of different groups. CONCLUSION: IFN-γ production starts at early stage of cutaneous leishmaniasis and enhance during course of lesion healing, IFN-γ level is significantly higher in all patients compared to healthy volunteers, IFN-γ is significantly higher in patients with healing form than non-healing form of lesion.

A Comparative Evaluation of Regulatory T Cells Profile among Acute and Chronic Cutaneous Leishmaniasis Using Flow Cytometry.

BACKGROUND: Cutaneous leishmaniasis (CL) is described as a major health problem in many countries of the world. Regulatory T cells (Tregs) are characterized as one of immunologic indexes. One of the best methods to determine of Tregs percentage is flow cytometry. The aim of this study was determination of the role of Tregs profile among acute and chronic forms of human CL using flow cytometry analysis. METHODS: This study was conducted on 24 patients referred to Laboratory of Leishmaniasis, Tehran University of Medical Sciences, Tehran, Iran with acute and 14 patients with chronic phases of CL as well as 15 healthy individuals as control group in 2015-2016. After microscopic examination, 2 ml of peripheral blood samples were collected for determining percentage of CD4 + CD25 + CD127 low Tregs by using flow cytometry method. RESULTS: Using flow cytometry analysis, the average percentage of Tregs were calculated 5.73, 6.71 and 6.61 for acute, chronic and healthy individuals, respectively. With SPSS software and Scheffe multiple comparison tests, the differences within in these groups are statistically significant (P=0.04) and between the acute and chronic group, there was marginally significant with approximately 91% of confidence level (P=0.088). CONCLUSION: Marginally differences were found significantly among averages of Regulatory T cells, acute and chronic phases of CL. Further comprehensive studies can be needed to verify the role of Tregs in both phases of CL cases.

Salivary and Serum Anti-Desmoglein 1 and 3 ELISA and Indirect Immunofluorescence in Pemphigus Vulgaris: Correlations with Serum ELISA, Indirect Immunofluorescence and Disease Severity.

Anti-desmoglein (anti-Dsg) ELISA and indirect immunofluorescence (IIF) are used for the diagnosis of pemphigus vulgaris (PV). The value of salivary ELISA, serum ELISA, and IIF in the diagnosis of PV, and the correlation of salivary anti-Dsg1 and anti-Dsg3 ELISA with serum ELISA, serum and salivary IIF titers, and disease severity in patients with PV were evaluated. Fifty newly diagnosed patients with PV were enrolled in the study. Demographic data and disease-severity scores were recorded for each patient. Anti-Dsg1 and anti-Dsg3 ELISA and IIF were performed on both serum and salivary samples. Given the cut-off value of 20 RU/mL for Dsg1 and Dsg3, serum Dsg1 and Dsg3 ELISA were positive in 41 (82%) and 40 (80%) patients, and saliva Dsg1 and the Dsg3 ELISA were positive in 2 (4%) and 3 (6%) patients, respectively. Using the cut-off value of 13.4 RU/mL and 7.7 RU/mL for Dsg3 and Dsg1 salivary ELISA, 25 (50%) and 23 (46%) patients tested positive for Dsg3 and Dsg1, respectively. Serum IIF results were positive in 35 (70%) patients, and salivary IIF results were positive in 16 (32%) patients. Salivary anti-Dsg1 and anti-Dsg3 showed moderate correlations with the total pemphigus disease area index (PDAI) score (r=0.466, P<0.001), (r=0.459, P<0.001), respectively. A moderate correlation between serum IIF and salivary IIF was also detected (r=0.413, P<0.001). Salivary anti-Dsg1 and anti-Dsg3 ELISA could be used as a safe and noninvasive method for the diagnosis of PV under certain circumstances, especially in children or elderly patients. Salivary ELISA is superior to salivary IIF.

Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris.

BACKGROUND: Pemphigus is a severe autoimmune blistering disease affecting the skin and mucosa. Mortality is high in the absence of treatment. Nowadays, treatment is based mainly on corticosteroids and cytotoxic drugs; however, because of the rarity of the disease worldwide, there is not yet a standard treatment based on randomized controlled trials, and the treatment used is based mainly on the experience of experts. OBJECTIVE: The aim of this study was to compare the efficacy and safety of 4 treatment regimens for pemphigus vulgaris: prednisolone alone, prednisolone plus azathioprine, prednisolone plus mycophenolate mofetil, and prednisolone plus intravenous cyclophosphamide pulse therapy. METHODS: One hundred twenty new cases of pemphigus vulgaris were enrolled. These patients were randomly allocated into 1 of 4 treatment groups (each comprising 30 patients) and received prednisolone (P), prednisolone and azathioprine (P/A), prednisolone and mycophenolate mofetil (P/MM), and prednisolone and intravenous cyclophosphamide pulse therapy (P/PC). They were followed up for 1 year at the Pemphigus Research Unit. RESULTS: In groups P, P/A, P/MM, and P/PC, 23 (76.5%), 24 (80%), 21 (70%), and 22 (73.3%) of the patients, respectively, followed the regimen for the full 1-year period. The mean total dose of prednisolone administered in groups P, P/A, P/MM, and P/PC was 11631 mg (standard deviation [SD] = 7742), 7712 mg (SD = 955), 9798 mg (SD = 3995), and 8276 mg (SD = 810), respectively. The mean total dose of prednisolone in group P (prednisolone alone) was 11,631 mg, The mean total dose of prednisolone in the 3 cytotoxic groups was 8652 mg. By using analysis of variance, the difference was statistically significant (P = .047). In the cytotoxic groups, there was a significant difference between the P/A and P/MM groups (P = .007), but not between P/A and P/PC (P = .971), and P/MM and P/PC (P = .670). Side effects were not significantly different among the 4 groups. LIMITATIONS: Larger sample sizes and blind design are suggested for future studies. CONCLUSION: The efficacy of prednisolone is enhanced when it is combined with a cytotoxic drug. The most efficacious cytotoxic drug to reduce steroid was found to be azathioprine, followed by cyclophosphamide (pulse therapy), and mycophenolate mofetil.