Enhanced monocyte and neutrophil cytotoxicity and normal cyclic nucleotide levels in severe psoriasis

Eighteen patients with active psoriasis were investigated for antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by monocytes and neutrophil leukocytes. Patients with extensive psoriatic lesions showed increased ADCC whereas patients with minimal psoriasis had normal mono cyte and neutrophil function. After clinical remission the ADCC became normal. No stimulatory factors in psoriatic serum could be demonstrated. The increased monocyte and neutrophil cytotoxicity in severe psoriasis is not explained by altered cyclic nucleotide levels as cAMP and cGMP levels were normal in psoriatic monocytes and neutrophils showing both increased and normal ADCC. Our results indicate that increased ADCC is secondary to the psoriatic activity.     

In vivo effects of PUVA on lymphocyte function

Eighteen patients with active psoriasis were investigated for antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by monocytes and neutrophil leukocytes. Patients with extensive psoriatic lesions showed increased ADCC whereas patients with minimal psoriasis had normal monocyte and neutrophil function. After clinical remission the ADCC became normal. No stimulatory factors in psoriatic serum could be demonstrated. The increased monocyte and neutrophil cytotoxicity in severe psoriasis is not explained by altered cyclic nucleotide levels as cAMP and cGMP levels were normal in psoriatic monocytes and neutrophils showing both increased and normal ADCC. Our results indicate that increased ADCC is secondary to the psoriatic activity.     

Colchicine in generalized pustular psoriasis: Clinical response and antibody-dependent cytotoxicity by monocytes and neutrophils

Summary Four patients with generalized pustular psoriasis were treated with oral colchicine in an open study. Three of the four patients went into total remission within two weeks while receiving colchicine. The monocyte- and neutrophil function was assessed by studying antibody-dependent cytotoxicity. Increased values observed before treatment decreased during treatment. The patient who responded poorest clinically also showed less changes in monocyte- and neutrophil antibody-dependent cytotoxicity.     

An in vitro assessment of certain cellular and humoral immune functions in patients with chronic acne

Testing of cellular and humoral immune functions was performed on nineteen patients with chronic acne. Eight patients had no detectable abnormality of cellular function, seven had low neutrophil motility and six had depressed mitogen induced lymphocyte transformation. Eight patients had raised levels of serum IgE, seven had positive CRP values and one had a total IgA deficiency. Following propranolol therapy five patients showed no evidence of clinical improvement and nine showed significant clinical and immunological improvement.     

The treatment of neurodermatitis and prurigo patients with the mineral springs of Andizhan Province

The efficacy of balneotherapy with local mineral water was estimated in 328 patients with neurodermatitis and 42 ones with prurigo. Besides balneotherapy, one group of patients was administered polychemotherapy including alpha-tocopherol, 30% sodium thiosulfate, ascorbic and nicotinic acids. Balneotherapy resulted in clinical remission in 25.7% of patients; a considerable improvement was achieved in 42% and less marked improvement in 28.1% of patients. The treatment efficacy depended on the disease duration and process dissemination. The mean duration of a remission was 12.2 months. Late results were much better after repeated courses of balneotherapy.     

过敏性紫癜患者外周血中性粒细胞CD11b及血浆弹性蛋白酶的检测

目的 探讨不同病期过敏性紫癜患者外周血中性粒细胞表面黏附分子CD11b的表达及血浆弹性蛋白酶活性的变化及其与疾病活动性的关系。方法 采用流式细胞仪检测12例过敏性紫癜患者活动期及缓解期外周血中性粒细胞表面黏附分子CD11b表达的变化,并与12例正常人进行比较。采用ELISA法检测20例过敏性紫癜患者活动期及缓解期血浆弹性蛋白酶水平的变化,并与20例正常人进行比较。结果 活动期患者外周血中性粒细胞CD11b的表达及血浆弹性蛋白酶水平明显高于缓解期（P均 < 0.01）;缓解期患者外周血中性粒细胞CD11b的表达与正常人对照组比较,差异无统计学意义（P ＞ 0.05）;缓解期患者血浆弹性蛋白酶水平仍高于正常人对照组（P ＜ 0.05）。在活动期,外周血中性粒细胞CD11b的表达与血浆弹性蛋白酶水平呈正相关（r ＝ 0.73,P < 0.01）;而缓解期两者无显著相关性（r ＝ 0.20,P > 0.05）。结论 过敏性紫癜患者外周血中性粒细胞处于激活状态,活动期较缓解期更明显。     

Porphyria cutanea tarda symptomatica (PCT-S). A study of the effect of phlebotomy therapy.

The effect of phlebotomy therapy on porphyrin metabolism was evaluated in five patients with porphyria cutanea tarda symptomatica (PCT-S). The removal of 2,500 to 4,500 cc over a three to four and one-half month period resulted in a marked reduction in urine and fecal uroporphyrin excretion in three of the subjects. Clinical improvement accompanied the chemical response in each case. In one patient, the induced chemical and clinical remission has persisted for six months without further treatment.     

Treatment of severe pemphigus with protein A immunoadsorption, rituximab and intravenous immunoglobulins

BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease usually treated with high-dose corticosteroids and other immunosuppressants. However, this regimen may prove inadequate in severe cases and cause dangerous side-effects. While protein A immunoadsorption (PAIA) induces a rapid remission in severe pemphigus, the disease usually recurs once the treatment is stopped. In contrast, anti-CD20 antibody rituximab has a delayed onset of action but may lead to a long-term remission of pemphigus. OBJECTIVE: To develop a treatment protocol combining the rapid remission induced by PAIA with the positive long-term effects of rituximab. PATIENTS AND METHODS: Five patients with pemphigus vulgaris and two patients with pemphigus foliaceus were treated with a combination of PAIA, rituximab and conventional immunosuppressants. Patients who failed to respond to this therapy subsequently received intravenous immunoglobulins (IVIg). RESULTS: All seven patients showed a sharp decline of circulating autoantibody levels and rapid improvement of cutaneous and mucosal lesions within 4 weeks of therapy. Long-term remission was induced in three patients and one further patient showed a partial improvement of his disease. The three remaining patients who could not be weaned off PAIA and remained resistant to rituximab treatment showed a good response to IVIg therapy. CONCLUSION: The combination of PAIA and rituximab induces a rapid and durable remission in a subset of patients with severe pemphigus. IVIg therapy appears to be a good treatment option for rituximab nonresponders.     

Treatment of refractory erosive oral lichen planus with extracorporeal photochemotherapy: 12 cases

BACKGROUND: Case reports have suggested that extracorporeal photochemotherapy (ECP) might be beneficial for the treatment of erosive oral lichen planus (OLP) recalcitrant to conventional immunosuppressive therapies. OBJECTIVES: To evaluate over a long-term period the clinical efficacy and toxicity of ECP in a series of patients with refractory OLP, and to monitor peripheral blood lymphocyte subset counts under treatment. METHODS: Twelve patients with refractory OLP underwent a standardized protocol of ECP. Sessions were performed twice weekly for 3 weeks, and then the treatment schedule was adapted according to clinical benefit. The disease severity was evaluated monthly on a clinical basis. Complete remission was defined as the absence of any erosion and partial remission as a decrease of at least 50% of erosion surface. Blood cell counts with CD4+ and CD8+ lymphocyte subsets were evaluated every 3 months. RESULTS: All patients showed a decrease of the erosive surface; nine (75%) achieved a complete remission and three (25%) a partial remission. Seven of the eight patients followed for more than 3 years had recurrences of erosions when ECP sessions became less frequent or were stopped. After resumption of an initially accelerated regimen of ECP, all again showed partial or complete remission. Blood lymphocyte counts decreased during treatment, without statistically significant changes in CD4+/CD8+ ratio, and increased during relapse. CONCLUSIONS: ECP is an effective alternative therapy in erosive OLP showing resistance to classical treatments. The decrease in blood lymphocyte counts appears to parallel the clinical improvement under treatment.     

Period of remission after treatment with UVA-1 in sclerodermic skin diseases

Background Sclerodermic skin diseases can cause severe morbidity and disability. UVA‐1 has shown to be an effective therapy for sclerodermic skin diseases. However, the period of remission in these patients is not clear. In this study, the effect and remission period of UVA‐1 phototherapy in various sclerotic skin diseases is described using a semiquantitative clinical score combined with the durometer score as an objective apparatus to measure the hardness of the skin. Objective Our purpose was to determine the effectiveness of UVA‐1 phototherapy and the duration of remission in sclerodermic skin diseases. Methods In this prospective study, 10 patients with various sclerodermic skin diseases were treated with UVA‐1 phototherapy. The durometer was used to observe the hardness of the skin. Hardness of the skin was measured by one investigator at 10 locations, distributed evenly on the representative sclerotic skin. Each spot was measured three times, and the average of each of these measurements was summed to give the total durometer score. Durometer scores were recorded weekly until the final treatment date and 4 weeks after treatment. Clinical scores were carried out at the end date of the treatment using a 6‐point scale semiquantitative score. Long‐term effects were evaluated up to 29–46 months. Results The patients were treated with UVA‐1 in a cumulative dose of 1286 ± 58.8 (SEM) J/cm² (range, 846–1470 J/cm²) divided over five times a week for 4 weeks. In all patients studied, the sclerotic skin lesions were markedly softer after UVA‐1 treatment. All durometer scores improved highly significant during the first 3 weeks of treatment and borderline significant during the last week of treatment. There was no significant improvement between the end of UVA‐1 phototherapy and 1 month after ending the therapy (P > 0.05). All patients noted improvement of the semiquantitative clinical score during treatment. Clinical improvement was associated with improvement of the durometer score (95% confidence interval). With a follow‐up until 46 months, the remission period was stable up to 26 months in six patients. The duration of sclerodermic skin diseases before start of treatment did not influence improvement in the clinical or durometer score. One patient had an acute side effect of minimal erythema. No other side effects, except tanning and fatigue, were noted. Limitations This is an open‐label uncontrolled study. Conclusion UVA‐1 is an effective treatment for sclerodermic skin diseases with a long period of remission and clinical improvement even in patients with a long history of a sclerotic skin disease. UVA‐1 should be considered among the first approaches in the management of sclerotic skin diseases.     

SUCCESSFUL TREATMENT OF A PATIENT WITH RECURRENT FURUNCULOSIS BY VITAMIN C: IMPROVEMENT OF CLINICAL COURSE AND OF IMPAIRED NEUTROPHIL FUNCTIONS

Background. Neutrophils play a critical role in host defense against a variety of microbial pathogens. There is much information to suggest a role for vitamin C in the physiology of neutrophils. Thus, the effects of vitamin C treatment were studied in a patient with a history of recurrent furunculosis who showed altered neutrophil functions. Methods. Superoxide generation was measured by cytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils and chemotaxis on agarose plates were determined. Results. Chemotaxis, phagocytosis, and superoxide generation of the patient's neutrophils were significantly lower than those of the matched control. Treatment with vitamin C (500 mg/day) for 30 days caused a dramatic clinical response and a significant improvement of all three neutrophil functions to values similar to those of the controls. Conclusions. We suggest that the patient described here had a temporary defect in neutrophil functions. The treatment with vitamin C probably prevented neutrophil oxidation, thus contributing to recovery of neutrophil function and arrest of furunculosis.     

Therapeutic effect of mizoribine on pemphigus vulgaris and pemphigus foliaceus

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan-Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0?μg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.     

Prognosis of 234 rosacea patients according to clinical subtype: The significance of central facial erythema in the prognosis of rosacea

Rosacea has a wide spectrum of clinical features, which include persistent facial redness, flushing, telangiectasia, inflammatory papules/pustules, hypertrophy and/or ocular features. The prognosis of rosacea according to clinical subtype has not been evaluated. We analyzed the prognosis of rosacea in 234 patients, which included 120 patients with mixed subtype, 75 with the erythematotelangiectatic rosacea subtype and 39 with the papulopustular rosacea (PPR) subtype. The prognosis of rosacea was classified as: (i) no improvement; (ii) partial remission; and (iii) complete remission. The frequencies of complete remission, time to complete remission and 1‐year complete remission rate were compared between subtypes. Follow‐up periods ranged 2–72 months (median follow‐up, 17.5). Aggravation of the disease was found in 50.4% of patients during follow up. Partial or complete remission was noted in 61.5% and 20.9% of patients, respectively. The median time to complete remission was 56.0 months. The prognosis of disease was more favorable for patients with the PPR subtype than for patients with other subtypes with respect to the frequency of complete remission, median time to complete remission and the 2‐year complete remission rate. In conclusion, papulopustular rosacea without remarkable centrofacial erythema showed a more favorable prognosis than other subtypes. Erythematotelangiectatic lesions in rosacea patients present a challenge for the treatment of rosacea.     

Ofuji's papuloerythroderma: two cases treated with azathioprine

BACKGROUND: Ofuji's papuloerythroderma is a rare disorder, characterized by a generalized pruriginous eruption, sparing the folds. It predominates in the elderly. The pathology is still unknown but associations with lymphoma have been described. Various therapeutic approaches have been tried, most often including local and general corticosteroids and PUVA. OBSERVATION: Two patients aged 71 and 84 years presented red pruriginous macular rash sparing the abdominal folds. Eosinophilia and lymphopenia were observed. Cutaneous biopsies showed dermal lymphocytic and plasmocytic infiltrates with, in one case, eosinophil and neutrophil exocytosis. Clinical, biological and morphological investigations showed no association with other diseases such as cancer or lymphoma. Azathioprine permitted clinical and biological remission in both patients but had to be interrupted because of minor side effects (infection, gastroenterologic disorders) and corticosteroids were introduced in one case. DISCUSSION: We suggest that histological aspects, such as exocytosis, may represent a link between Ofuji's papuloerythroderma and lymphoma. Azathioprine led to clinical and biological improvement in our 2 patients. Because of its adverse effects, it could be proposed as second-line therapy in patients presenting resistance or intolerance to usual treatments.     

Pharmacological modulation of neutrophil phagocytic function in a patient with recurrent sepsis, pyoderma gangrenosum and impaired phagocytosis

A 50-year-old man with recurrent life-threatening sepsis and a cutaneous condition resembling pyoderma gangrenosum, was found to have a defect of neutrophil phagocytic function. Phagocytosis could be enhanced by corticosteroids, both in vitro in a dose-dependent manner, and in vivo, when it was accompanied by rapid clinical improvement. Studies with steroid hormones and immuno-stimulatory drugs are described.     

The Role of the Nervous System in the Pathophysiology of Psoriasis: A Review of Cases of Psoriasis Remission or Improvement Following Denervation Injury

As most efforts in the last decade have focused on the immunologic basis of inflammatory skin disease, there has been less emphasis on the role of the nervous system in the disease process of psoriasis. Evidence in support of the neurocutaneous pathway has come from observations of patients experiencing unilateral improvement and even complete remission following nerve damage in the affected dermatomal region. The aim of this review was to investigate the role of neuropeptides in the intricate pathophysiology of psoriasis. The PubMed database was searched for individual case reports or case series that reported clearance or significant improvement in psoriatic disease in patients following documented nerve injury. A total of 11 cases were found that reported improvement of psoriatic lesions in areas afflicted by central or peripheral nerve injury. The most common causes of denervation were inadvertent surgical interruption, cerebrovascular accident, and poliomyelitis. In four cases the patients eventually regained neurologic function, which was associated with a recurrence of skin lesions. In cases of permanent nerve damage, there was remission of psoriasis. The cases reported in the literature to date provide clinical evidence that absence of neural input leads to psoriasis improvement, suggesting a crucial role of the nervous system in the pathophysiology of psoriatic disease. In fact, neuropeptides such as nerve growth factor, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide may be important contributors of psoriatic disease and potential targets for future therapies.     

窄谱中波紫外线治疗顽固性特应性皮炎临床研究

目的：观察窄谱中波紫外线治疗顽固性特应性皮炎的疗效、近期副作用及患者依从性。方法：对20例顽固性特应性皮炎患者进行窄谱中波紫外线全身照射治疗，每周3次，共8周；在治疗前及治疗8周后用EASI标准进行病情评分，计算病情改善率。结果：20例患者中19例均完成8周的治疗；治疗8周后3例患者基愈，9例显效，6例有效，1例无效，平均病情改善率为55．11％。3例患者出现全身轻度色素沉着，随访6个月3例基愈患者未见复发。结论：对顽固性特应性皮炎，窄谱中波紫外线显示出较好的治疗效果，且近期副作用少，患者依从性好，复发少。     

Treatment of severe atopic dermatitis with extracorporeal photopheresis

Extracorporeal photopheresis using UVA irradiation of enriched lymphocytes in the presence of 8-methoxypsoralen (8-MOP) as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. We report on the first three patients subjected to extracorporeal photopheresis for severe atopic dermatitis. All patients had a lifelong history of atopic skin inflammation, and their disease had finally become resistant to well-established therapeutic regimes. Extracorporeal photopheresis resulted in a marked clinical improvement in the skin lesions of all patients. The decrease in cutaneous inflammatory activity became evident by the end of the second photopheresis cycle. In two patients skin lesions had virtually disappeared after the fifth treatment cycle, while in the third patient a lasting and substantial improvement in pruritus and erythema was achieved. Clinical remission was stable under maintenance therapy with prolonged intervals between photopheresis sessions. Therapeutic efficacy was reflected by a marked reduction in IgE serum levels in all three patients, while serum concentration of IgG, IgM and IgA as well as the profile of circulating lymphocytes remained essentially unchanged. No clinical signs of immunosuppression or other severe adverse events became evident. Collectively, our preliminary results indicate that extracorporeal photopheresis may interfere with the pathomechanisms leading to atopic dermatitis and therefore should be considered as a treatment modality for severe forms of this recalcitrant disorder.     

Management of necrotizing vasculitis with colchicine. Improvement in patients with cutaneous lesions and Behcet's syndrome

Six patients with necrotizing vasculitis were treated with oral colchicine as part of an open study. Four patients with cutaneous vasculitis and normal levels of serum complement and one patient with vasculitis associated with Behcet's syndrome demonstrated clinical improvement while receiving colchicine. One patient with cryoglobulinemia, hypocomplementemia, and cutaneous vasculitis showed no response to colchicine therapy. In three patients, clinical improvement persisted after its withdrawal. Colchicine may be effective in controlling cutaneous necrotizing vasculitis and Behcet's syndrome through its effect on polymorphnuclear leukocyte function.     

A prospective observational study to compare efficacy of topical triamcinolone acetonide 0.1% oral paste,oral methotrexate,and a combination of topical triamcinolone acetonide 0.1% and oral methotrexate in moderate to severe oral lichen planus

Topical corticosteroids are considered to be the most effective treatment for oral lichen planus (OLP). Methotrexate has been found to be effective in extensive cutaneous lichen planus. The objectives of the study were to evaluate the clinical efficacy and safety of topical triamcinolone 0.1% oral paste, oral methotrexate and a combination of these in symptomatic moderate‐to‐ severe OLP. Forty‐five patients were recruited and were allocated to three treatment arms with 15 patients in each treatment arm. They were treated for a period of 16 weeks or until complete clinical remission, whichever was earlier. The parameters assessed were clinical severity score, visual analogue score, and quality of life impairment questionnaire score. Forty‐three patients completed the study. All three treatment modalities were effective. The patients in the combination group had significantly better reduction in the outcome parameters assessed compared to the other two groups. Nine patients achieved complete clinical remission, 6 in the combination group and 3 in the topical triamcinolone group. Systemic methotrexate, alone or in combination with topical triamcinolone, is effective in management of moderate to severe OLP.