Biomedical subjects

A Razzaque Ahmed

Publications and source records attributed to A Razzaque Ahmed.

At least 19 recordsLinked to original sources

PubMed2007

Relationship between cancer and oral pemphigoid patients with antibodies to alpha6-integrin.

BACKGROUND: Mucous membrane pemphigoid is an autoimmune mucocutaneous blistering disease. A subset, known as anti-epiligrin cicatricial pemphigoid is associated with a high risk for malignancy. Oral pemphigoid (OP) is limited to the oral cavity. The purpose of this study was to determine the association between malignancy and patients with OP with antibodies to alpha6-integrin subunit. METHODS: We determined the incidence of cancer in 72 patients with OP and compared it to the expected incidence using age and sex-specific rates of malignancy in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) Registry. RESULTS: During a mean observation period of 9.1 years (range: 2.8-40), for 70, three OP patients developed malignancies. The expected number of cancers based on the NCI SEER Registry was 8.83. The relative risk for cancer in OP patients, with autoantibodies to alpha6-integrin, was 0.34 (95% CI, 0.07-0.99, P < 0.05). CONCLUSION: It appears that patients with OP, with antibodies to alpha6, may have a possible reduced relative risk for developing cancer.

Adult↗

PubMed2006

Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin.

BACKGROUND: Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous blistering disease. Conventional therapy consists of high-dose corticosteroids, immunosuppressive agents, and intravenous immune globulin. METHODS: We studied patients with refractory pemphigus vulgaris involving 30% or more of their body-surface area, three or more mucosal sites, or both who had inadequate responses to conventional therapy and intravenous immune globulin. We treated the patients with two cycles of rituximab (375 mg per square meter of body-surface area) once weekly for 3 weeks and intravenous immune globulin (2 g per kilogram of body weight) in the fourth week. This induction therapy was followed by a monthly infusion of rituximab and intravenous immune globulin for 4 consecutive months. Titers of serum antibodies against keratinocytes and numbers of peripheral-blood B cells were monitored. RESULTS: Of 11 patients, 9 had rapid resolution of lesions and a clinical remission lasting 22 to 37 months (mean, 31.1). All immunosuppressive therapy, including prednisone, could be discontinued before ending rituximab treatment in all patients. Two patients were treated with rituximab only during recurrences and had sustained remissions. Titers of IgG4 antikeratinocyte antibodies correlated with disease activity. Peripheral-blood B cells became undetectable shortly after initiating rituximab therapy but subsequently returned to normal values. Side effects that have been associated with rituximab were not observed, nor were infections. CONCLUSIONS: The combination of rituximab and intravenous immune globulin is effective in patients with refractory pemphigus vulgaris.

Adolescent↗

PubMed2006

Antigen specificity in subsets of mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) has several subsets based on target antigens recognized by their sera. MMP and ocular cicatricial pemphigoid (OCP) sera recognize beta4 integrin subunit, oral pemphigoid sera recognize alpha6 integrin subunit, and anti-epiligrin cicatricial pemphigoid sera recognize laminin 5. Our aim is to determine if autoantibodies in the sera of patients with MMP, OCP, and oral pemphigoid (OP) recognize only their target antigens, and to see if this specificity is maintained throughout the clinical course. An immunoblot assay using bovine gingival lysate was used as substrate. Fifteen MMP patients, eight with OCP, and 15 OP patients were studied before therapy and at multiple intervals during the clinical course. Absorption and blocking studies were performed to determine binding specificity. Sera of patients with MMP and OCP recognize only beta4 integrin subunit, and sera of OP patients recognize alpha6 integrin throughout the clinical course. The sera of patients in the subsets of MMP described in this report show adherence and selectivity to target antigen during the entire clinical course, without crossover, interaction, or change. Hence, these subsets of MMP provide an excellent model to study clinical correlation with antigen and antibody specificity, in autoimmunity.

Antibody Specificity↗

PubMed2006

Pathogenic human monoclonal antibody against desmoglein 3.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune mucocutaneous disease associated with production of IgG autoantibodies to desmoglein 3 (Dsg3), a 130-kDa epidermal cadherin protein. The binding of pathogenic antibody to Dsg3 on epidermal keratinocytes leads to loss of intercellular adhesion and results in intraepithelial blister formation. Here, we describe a human monoclonal antibody, PVMAB786, a Dsg3-specific IgG4 antibody, from an untreated patient with active PV. The antibody reacts with a 130-kDa protein on keratinocyte cell surfaces and recombinant Dsg3 protein, but not desmoglein 1 protein. PVMAB786 induces acantholysis in normal human skin and mucous membranes and induces a clinical and histological profile similar to human PV when injected into neonatal mice. PVMAB786 will be a valuable tool in identifying the role of Dsg3 in epithelial cell adherence and acantholysis, mechanisms of Dsg3 processing/presentation and V gene and isotype usage in PV pathogenesis.

Acantholysis↗

PubMed2006

Identification of an epitope within human integrin alpha 6 subunit for the binding of autoantibody and its role in basement membrane separation in oral pemphigoid.

Oral pemphigoid (OP) is a rare chronic autoimmune disease characterized by blisters and erosive lesions in the oral mucosa. We identified an epitope for the binding of OP autoantibodies within the integrin alpha6 subunit, by cloning four overlapping fragments (A, B, C, and D). Immunoperoxidase studies demonstrated that all of the fragments were present in the oral mucosa. Sera of 20 patients with active OP were studied. All sera bound to integrin alpha6 in DU145 cell lysate by immunoprecipitation and immunoblot assay. The same sera bound only to fragment A and its subfragment A2 on an immunoblot assay. The specificity of the binding was further characterized by blocking and cross-absorption studies. A 14-aa synthetic peptide A2.1, within fragment A2, bound to all the test sera. The sera in this study bound to only one epitope. Controls were sera samples from 10 healthy volunteers and 40 patients with other variants of mucous membrane pemphigoid and mAb GoH3 and BQ16 to integrin alpha6. Control sera did not bind to the full-length integrin alpha6 subunit nor any of the cloned fragments. The OP patient sera and immunoaffinity-purified OP sera, rabbit antisera against fragments A and A2, and mAb GoH3 produced basement membrane separation of oral mucosa in organ culture. This study identifies a peptide within the extracellular domain of integrin alpha6 molecule, to which Abs in the sera from patients with OP bind, and which may play an important role in the pathogenesis of OP.

Autoantibodies↗

PubMed2006

Chronic cicatrizing conjunctivitis in a patient with epidermolysis bullosa acquisita.

OBJECTIVE: To describe a nonconventional diagnostic technique used to diagnose a case of cicatrizing conjunctivitis associated with epidermolysis bullosa acquisita. METHODS: Direct immunofluorescence of a biopsy specimen of the patient's conjunctiva was performed using fluorescein-conjugated rabbit antihuman antibodies against IgA, IgG, and IgM; complement C3; and fibrinogen. Immunoblot assay using healthy human skin as substrate was performed to investigate for the presence of antibodies in the patient's serum. After the diagnosis of systemic autoimmune disease was established, intravenous immunoglobulin therapy was administered. RESULTS: Direct immunofluorescence of the conjunctiva revealed linear deposition of IgA and IgG, and C3 at the epithelial basement membrane zone. Immunoblot analysis demonstrated the presence of IgG antibodies in patient serum directed against a 290-kDa protein in human skin. A diagnosis of epidermolysis bullosa acquisita was established. All signs and symptoms improved dramatically 4 months after initiation of intravenous immunoglobulin therapy and remained stable during follow-up. CONCLUSIONS: Epidermolysis bullosa acquisita can manifest in the eye as chronic cicatrizing conjunctivitis indistinguishable from ocular cicatricial pemphigoid. A nonconventional diagnostic tool (immunoblot assay) might be helpful in establishing the diagnosis of an underlying systemic autoimmune disease in patients with chronic cicatrizing conjunctivitis. Intravenous immunoglobulin therapy was effective against chronic cicatrizing conjunctivitis associated with epidermolysis bullosa acquisita.

Adult↗

PubMed2006

Anal involvement in pemphigus vulgaris.

INTRODUCTION: Anal involvement in patients with pemphigus vulgaris has rarely been reported. We report 16 pemphigus vulgaris patients with anal involvement. METHODS: We retrospectively reviewed the clinical data on 16 patients treated at a tertiary dermatology referral center. RESULTS: Of 16 patients with anal involvement of pemphigus vulgaris, ten were female and six were male. The mean age of onset was 56 (range, 37-82) years. All patients had involvement of pemphigus vulgaris at multiple sites, including oral involvement. Recurrent episodes of anal pemphigus vulgaris were noted in nine (56 percent) patients, with a mean of 2.4 recurrences (range, 1-11). In all patients, pemphigus vulgaris was controlled with systemic and local therapy. Long-term follow-up for a mean of 53 (range, 4-188) months indicated that no long-term sequela occurred because of anal involvement. CONCLUSIONS: Anal involvement in pemphigus vulgaris is not very common and generally occurs in patients with severe disease. With appropriate topical and systemic therapy, patients have full recovery with no sequelae.

Adrenal Cortex Hormones↗

PubMed2006

Dual diagnosis of pemphigus vulgaris and connective tissue disease.

This is a retrospective analysis of patients with pemphigus vulgaris and connective tissue disease (CTD) present as systemic lupus erythematosus, mixed CTD, or both. Pemphigus vulgaris was severe, difficult to treat, but eventually responded to therapy, resulting in a remission. In 6 patients, the CTD was stable and controlled with symptomatic therapy, and in 7 patients required systemic therapy. Life-threatening systemic involvement in systemic lupus erythematosus or mixed CTD-such as renal, cardiac, and neurologic-were absent in these patients on 8 years (range 3-18 years) of follow-up. There are two limitations to this study. First, it is a retrospective study. Second, no other disease control groups were used for comparison purposes.

Aged↗

PubMed2006

Rituximab: a monoclonal antibody to CD20 used in the treatment of pemphigus vulgaris.

BACKGROUND: Rituximab is an anti-CD20 chimeric antibody that selectively targets B lymphocytes. Recently, it has been reported to be beneficial in treating pemphigus vulgaris. OBJECTIVE: Our aim was to review the English-language literature on the treatment of pemphigus vulgaris (PV) with rituximab and to determine its efficacy and influence on clinical outcome(s). MATERIAL AND METHODS: A retrospective review of the literature on the use of rituximab in the treatment of PV was conducted. Seventeen patients in 10 reports were described and their data were reviewed. RESULTS: The majority of patients received one course of rituximab along with conventional immunosuppressive therapy as concomitant therapy; 88% of the patients demonstrated improvement. More than half of the patients were followed up for more than 6 months after rituximab treatment; they appeared to be clinically disease free, but were still receiving conventional immunosuppressive therapy. Side effects in most patients were transient and infusion related. Serious infections occurred in 4 patients. One patient died. LIMITATIONS: The sample size of this study is small; there is no uniformity of data collection or measurement of key and critical indices, and follow-up was limited. CONCLUSION: Rituximab may be a promising agent in treatment of PV.

Antibodies↗

PubMed2006

Efficacy of intravenous immunoglobulin treatment in refractory uveitis.

PURPOSE: To assess the efficacy of intravenous immunoglobulin (IVIg) therapy in patients with severe uveitis otherwise unresponsive to conventional immunomodulatory agents. METHODS: Data on five consecutive patients treated with IVIg and followed to the present time by one of the authors (CSF) were reviewed. All patients had severe and recalcitrant uveitis of diverse etiologies. Main outcome measures were control of intraocular inflammation, steroid-sparing effect, visual acuity, and side effects. RESULTS: The duration of IVIg therapy was 3 to 36 months (mean, 16.8 months). Treatment was effective in controlling the intraocular inflammation in 3 of 5 patients. One of those patients required maintenance of systemic steroids at a dose of 10 mg per day. Visual acuity has stabilized or improved in these three patients. No immediate or long-term side effect was observed in any of the patients. CONCLUSIONS: Intravenous immunoglobulin therapy was an effective therapeutic modality in the treatment of three of five patients with severe uveitis that was unresponsive to conventional immunomodulatory agent(s). No adverse events were observed.

Adolescent↗

PubMed2005

Use of intravenous immunoglobulin therapy in autoimmune blistering diseases.

Autoimmune mucocutaneous blistering diseases (AMBD) are an interesting group of rare diseases that affect the mucous membranes and the skin and are frequently or potentially fatal. The clinical presentation is significantly variable, as is the course and prognosis. The immunopathology is well characterized and the target antigens to which the autoantibodies are directed have been studied by various investigators. A significant majority of the patients respond to conventional therapy, which consists of high-dose long-term systemic corticosteroids and immunosuppressive agents. This treatment program has significantly improved the prognosis in many patients. In such patients, significant side effects of the drugs may appear and produce a very poor quality of life. In patients with progressive diseases, especially those with mucous membrane pemphigoid, the significant sequela; such as blindness, aphonia, and stenosis of the anal and vaginal canals can occur. In several patients treated with conventional immunosuppressive therapy, death occurs as a consequence of prolonged immune suppression leading to opportunistic infections. In this manuscript, the published data on the use of immunoglobulins intravenous (IGIV) in patients with AMBD is presented. The most important features of IGIV in patients with AMBD are: 1) the ability to clinically control the disease; 2) the ability to induce and maintain a long-term clinical remission; 3) a lower incidence of side effects; and 4) a higher quality of life. The important characteristic of the IGIV therapy in the AMBD is two-fold. First, the therapy, when given according to a published protocol, produces a lasting and long-term clinical remission, rather than a temporary arrest of the disease. Second, the therapy, as described in the protocol, has a very definitive endpoint. Consequently, once the patients are treated and go into long-term remission, the therapy is no longer required. The significant positive results obtained with IGIV are to a large extent also due to the associated aggressive topical therapy that was used and the frequent use of sublesional injections with triamcinolone. The rapid and early detection of cutaneous and mucosal infections and their treatment with systemic antibiotics is also a very important feature of IGIV therapy. When patients are under long-term conventional therapy, the infections are often not detected because they lack the ability to mount signs of inflammation. It is also becoming increasingly clear for patients to have a successful outcome, in treatment with IGIV therapy, it is critical that the physician spends a significant amount of time with each patient, monitor the therapy closely, and be familiar with the overall health of the patient. It is also best if the therapies are instituted by a physician who has significant interest and experience in blistering diseases and IGIV therapy.

Adrenal Cortex Hormones↗

PubMed2005

Future horizons.

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Autoimmune Diseases↗

PubMed2005

Cost of intravenous immunoglobulin therapy versus conventional immunosuppressive therapy in patients with mucous membrane pemphigoid: a preliminary study.

BACKGROUND: Intravenous immunoglobulin (IVIG) is an expensive biologic agent used to treat patients with mucous membrane pemphigoid (MMP) nonresponsive to conventional immunosuppressive therapy (CIST). The high cost of IVIG is of concern to healthcare providers and insurance companies. OBJECTIVE: To compare the cost of IVIG with that of CIST in treating a cohort of 15 patients with severe and extensive MMP. METHODS: Fifteen patients with biopsy-proven MMP nonresponsive to CIST were subsequently treated with IVIG and demonstrated a positive clinical response. This was a comparative, retrospective study; the mean total duration of the observation period was 8.4 years. A comparison of the cost of IVIG with that of CIST during the study period and the annual cost was performed. The cost of CIST was defined as the actual cost of the drug plus the cost of management of the multiple adverse effects, including hospitalizations, produced by CIST. In the same patient cohort, no significant adverse effects to IVIG were observed and no hospitalizations were required. Hence, the cost of IVIG therapy is simply the actual cost of the IVIG. RESULTS: In this cohort of patients, CIST had significant adverse effects, many of which were hazardous and required prolonged and frequent hospitalizations. The mean total cost using IVIG therapy was significantly less than that of CIST during the entire course of the disease (p < 0.001) and on an annual basis (p < 0.05). CONCLUSIONS: IVIG therapy is a safe, clinically beneficial, and less-expensive alternative treatment in patients with progressive MMP that is nonresponsive to CIST.

Aged↗

PubMed2005

Ocular pemphigus.

BACKGROUND: Ocular involvement in patients with pemphigus vulgaris (PV) has been rarely reported. We report ocular involvement in 11 patients with PV. METHODS: Medical records of 11 biopsy-proven patients with PV treated during the period between 1990 and 2003 were reviewed and clinical information was analyzed. RESULTS: Mean age at onset of PV was 52.3 years (range, 30-80 years). Ocular disease was preceded by involvement of the skin, other mucosae, or both in all patients. Ocular involvement was limited to the conjunctivae, the eyelids, or both. PV did not affect the visual acuity of any of the patients. Suprabasal acantholysis was observed on routine histologic examination of the conjunctiva and skin of the eyelid. Direct immunofluorescence of perilesional eyelid skin demonstrated deposition of IgG on epithelial cell surface. Mean duration of follow up was 48.9 months (range, 4-100 months). Recurrence of ocular disease occurred in 3 patients; recurrence at nonocular mucosae occurred in 4 patients. No sequelae were observed during detailed follow-up. Ocular pemphigus improved with systemic therapy. The mean remission period was 32 months (range, 0-92 months). CONCLUSIONS: Ocular involvement in PV is rare. Involvement is limited to the conjunctiva, the eyelids, or both. PV does not appear to affect visual acuity. Patients have full recovery without sequelae.

Acantholysis↗

PubMed2005

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature.

OBJECTIVE: To perform a comprehensive review of Stevens-Johnson syndrome and toxic epidermal necrolysis. DATA SOURCES: A MEDLINE search was performed for the years 1975 to 2003 using the keywords Stevens-Johnson syndrome and toxic epidermal necrolysis to identify relevant articles published in English in peer-reviewed journals. STUDY SELECTION: All clinical studies that reported on 4 or more patients, review articles, and experimental studies that concerned disease mechanisms were selected and further analyzed. Clinical reports that included fewer than 4 patients were selected only if they were believed to carry a significant message about disease mechanism or therapy. RESULTS: Stevens-Johnson syndrome and toxic epidermal necrolysis seem to be variants of the same disease with differing severities. A widely accepted consensus regarding diagnostic criteria and therapy does not exist at present. Despite the recent experimental studies, the pathogenic mechanisms of these diseases remain unknown. Although progress in survival through early hospitalization in specialized burn units has been made, the prevalence of life-long disability from the ocular morbidity of Stevens-Johnson syndrome and toxic epidermal necrolysis has remained unchanged for the past 35 years. Further progress depends on modification of the acute phase of the disease rather than continuation of supportive care. The available published evidence indicates that a principal problem in the pathogenesis is immunologic and that immunomodulatory intervention with short-term, high-dose intravenous steroids or intravenous immunoglobulin holds the most promise for effective change in survival and long-term morbidity. CONCLUSIONS: The results of this review call for a widely accepted consensus on diagnostic criteria for Stevens-Johnson and toxic epidermal necrolysis and multicenter collaboration in experimental studies and clinical trials that investigate disease mechanisms and novel therapeutic interventions, respectively.

Adolescent↗

PubMed2005

Involvement of the female genital tract in pemphigus vulgaris.

BACKGROUND: Involvement of the genital tract in women with pemphigus vulgaris has rarely been reported. We report 34 patients with pemphigus vulgaris who have involvement of the vulva, vagina, or both. METHODS: We reviewed the clinical data on 34 women treated at a tertiary dermatology referral center from July 1988 to June 2005. RESULTS: Of 34 patients, 21 had labial involvement, 3 had vaginal involvement, and 10 had both labial and vaginal involvement. The mean age of onset of pemphigus vulgaris was 49 years. All patients had pemphigus vulgaris involvement at multiple other sites, and all had other mucous membrane involvement, most commonly oral (97%). Recurrent episodes of genital pemphigus vulgaris were noted in 35%, with a mean of 6 recurrences (range 1-11). In all the patients the pemphigus vulgaris was controlled with systemic and local therapy. Long-term follow-up for a mean of 76 months (range 9-204) indicated that no long-term sequela occurred due to genital involvement. CONCLUSION: Involvement of the female genital tract in pemphigus vulgaris is rare. Vulvar lesions occur more commonly than vaginal lesions. With appropriate topical and systemic therapy, patients can have full recovery with no sequelae. LEVEL OF EVIDENCE: II-3.

Adolescent↗

PubMed2004

A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies.

The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1). presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2). entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3). presence of conventional immunosuppressive therapy at the time of ocular involvement; (4). a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.

Aged↗

PubMed2004

Profile of autoantibody to basement membrane zone proteins in patients with mucous membrane pemphigoid: long-term follow up and influence of therapy.

Mucous membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the basement membrane zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy.

Adult↗