Objective To investigate the possible correlation of levels of circulating anti-BP180 autoantibodies with disease activity in bullous pemphigoid (BP). Design Diagnostic study. Setting Regional referral center at a university dermatology department. Patients Fifteen patients with typical clinical, histologic, and immunofluorescence findings of BP who had not received prior systemic treatment. Interventions Initially, 6 consecutive patients with BP were treated with oral doxycycline and niacinamide. Subsequently, 9 consecutive patients with BP received a combination of oral dapsone and prednisolone. Main Outcome Measures Disease activity, serum levels of autoantibodies to BP180, and titers of anti–basement membrane zone autoantibodies were assayed before initiation of treatment and 4 and 8 weeks later. Reactivity to BP180 was analyzed by enzyme-linked immunosorbent assay using a recombinant form of BP180 NC16A. Titers of anti–basement membrane zone autoantibodies were assayed by indirect immunofluorescence on 1-mol/L sodium chloride–split human skin. Results In both treatment groups, disease activity correlated with serum levels of autoantibodies to BP180 NC16A ( P = .004 [dapsone-prednisolone] and .007 [doxycycline-niacinamide]). No correlation was seen between disease activity and indirect immunofluorescence reactivity ( P = .18 and .16, respectively). In patients receiving dapsone plus prednisolone, the dose of corticosteroids necessary to suppress new blister formation correlated with anti-BP180 reactivity ( P = .002). Conclusions In contrast to indirect immunofluorescence reactivity that reflects reactivity to both BP180 and BP230, serum levels of autoantibodies to BP180 correlate with disease activity in BP. Assaying reactivity to BP180 should be a helpful guide for the therapeutic management of patients with this disease. Our results underline the pathogenic relevance of autoantibodies to human BP180.

https://jamanetwork.com/journals/jamadermatology/articlepdf/189943/dst9032.pdf

Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid.

https://www.cidjournal.com/article/S0738-081X(01)00188-2/pdf

Antioxidants and vitamins in cosmetics

Background and Design: The combination of nicotinamide and tetracycline has been anecdotally reported to be effective in the treatment of bullous pemphigoid. We conducted a randomized, open-labeled trial comparing the combination of 500 mg of nicotinamide, three times daily, and 500 mg of tetracycline four times daily, with prednisone therapy in 20 patients with bullous pemphigoid. The study was divided between an 8-week acute phase with fixed drug dosages and a 10-month follow-up phase in which study medications were tapered based on patient response. Results: Eighteen of 20 patients enrolled in the study were treated, two patients were unavailable for follow-up. Twelve patients were treated with the combination of nicotinamide and tetracycline and six patients were treated with prednisone. There were five complete responses, five partial responses, one nonresponder, and one patient with disease progression in the nicotinamide and tetracycline group compared with one complete response and five partial responses in the predni- sone group. There were no statistically significant differences in response parameters between the two groups. All five patients in the nicotinamide and tetracycline group receiving long-term follow-up remained disease free during medication tapering, while three patients in the prednisone group had repeated disease flareups with steroid tapering. Adverse effects in the nicotinamide and tetracycline group included gastrointestinal upset (two patients) and transient renal failure (one patient). In the prednisone group, there was one occurrence each of hypertension, erosive gastritis, multiple decubitus ulcers, osteomyelitis, deep venous thrombosis, and death related to sepsis. Two patients required insulin therapy for hyperglycemia. Conclusions: The combination of nicotinamide and tetracycline appears to be a useful alternative to systemic steroids in the treatment of bullous pemphigoid. (Arch Dermatol. 1994;130:753-758)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=DERM&articleId=555806&pdfFileName=archderm_130_6_010.pdf

Nicotinamide and Tetracycline Therapy of Bullous Pemphigoid

Background. Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance.

Methods. In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating.

Results. After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; −60%, nicotinamide vs. −43%, clindamycin, P = 0.168), and acne severity (−52% nicotinamide group vs. −38% clindamycin group, P = 0.161).

Conclusions. These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.

Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.

Pemphigus usually requires long-term therapy with oral corticosteroids, which can cause significant morbidity. 1, 2 Several immunomodulating drugs, such as cyclophosphamide, azathioprine, and gold have proved beneficial as steroid-sparing agents.3, 4 However, these agents also have limited long-term utility because of their potential to induce renal and hepatic dysfunction and bone marrow suppression. Nicotinamide in combination with tetracycline has been reported to be effective for bullous pemphigoid (BP) and linear IgA bullous dermatosis (LABD),S,6 This regimen has the advantage of lower toxicity compared with corticosteroids and immunosuppressant regimens. We have treated 11 cases of pemphigus and two cases of LABD with nicotinamide and tetracycline and report our experience,

https://www.jaad.org/article/S0190-9622(08)80651-2/pdf

Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: A review of 13 cases

The component in human transfer factor (TF) (Fraction IV, from exclusion chromatography on Sephadex G-25) responsible for suppression of antigen-induced lymphocyte transformation was previously identified as nicotinamide. Commercially available nicotinamide was subsequently shown to produce suppression of antigen-induced responses in vitro previously observed with TF Fraction IV. Nicotinamide was found to be nontoxic at the highest concentrations employed (10-2 M) and suppressive over a relatively broad range (10-5 to 10-2 M). The suppression appeared to be related to the magnitude of antigen- or mitogen-induced transformation and was apparent even when nicotinamide was added as late as 48 hr after stimulant addition.

Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor.

Human transfer factor (TF) was fractionated by exclusion chromatography and the fractions were tested for biologic activity in vivo and in vitro. Specific TF activity in vivo was found to reside in the major UV-absorbing peak (Fraction III). Fraction III eluted at 2.7 × V 0 and transferred tuberculin, candida, or KLH-reactivity to previously negative recipients. Fraction III from nonreactive donors was ineffective. When the fractions were tested in vitro, we found that both the mitogenic activity of whole TF and the suppressive activity to mitogen activation when present in TF was found in Fraction I. Fraction III contained components responsible for augmentation of PHA and PWM responses. In addition, Fraction III contained the component responsible for antigen-dependent augmentation of lymphocyte transformation. Fraction IV was suppressive to antigen-induced lymphocyte transformation. These data suggest that TF preparations contain components which can affect immune reactions in both specific and nonspecific ways.

Human Transfer Factor: Fractionation and Biologic Activity

Transfer factor preparations from 57 different donors have been compared for effects on mitogen- and antigen-induced lymphocyte transformation. Nine of the preparations were mitogenic when added to cultured lymphocytes although the magnitude of this activity was relatively low. The majority of the preparations (48/57) did not affect PHA-induced lymphocyte transformation although augmentation (6 of 57) and suppression (3 of 57) was observed with some. In addition we observed that most of the preparations tested suppressed ConA stimulation and augmented the PWM response. When selected preparations were evaluated on antigen-responsive cells, there was a correlation between the magnitude of antigen responsiveness and the magnitude of TF augmentation of antigen-induced lymphocyte transformation (p

Human Transfer Factor: Effects on Lymphocyte Transformation

This study was designed to elucidate the mechanism of the leukocyte adherence inhibition (LAI) test in man. To identify the reactive cell types, enriched leukocyte populations (dextran-separated leukocytes and Hypaque-Ficoll-isolated mononuclear cells and neutrophils, as well as rosette-isolated B- and T-lymphocytes) were tested for leukocyte adherence in the absence of serum to tumor-specific antigens. LAI reactivity was not restricted to any of the enriched populations, suggesting the involvement of multiple cell types. Attempts to demonstrate soluble lymphocyte factors in the LAI mechanism have been uniformly negative. In contrast, factors in serum of immune donors were able to arm naive cells to be specifically responsive. This suggests a role for serum factors in the mechanism of LAI reactivity and partially explains the participation of multiple cell types in the responses observed. In additional studies, we could not document a correlation between the magnitude of the dermal test (delayed cutaneous hypersensitivity) and the magnitude of the LAI response in patients with squamous cell carcinoma of the head and neck. In 34 of 54 of these patients, there was agreement between the two tests (both positive, 27 of 54; both negative, 7 of 54). In the remaining 20 patients, the dermal test was >5 mm while the LAI test was negative (<30% inhibition).

https://cancerres.aacrjournals.org/content/canres/39/2_Part_2/597.full.pdf

Finke P

Papers

Nicotinamide: suppression of lymphocyte transformation with a component identified in human transfer factor.

Human Transfer Factor: Fractionation and Biologic Activity

Human Transfer Factor: Effects on Lymphocyte Transformation

Assessment of the Mechanism of the Leukocyte Adherence Inhibition Test