Sarcoidosis: thalidomide treatment in ten patients]

BACKGROUND: Acute cutaneous sarcoidosis is generally spontaneously regressive but persistent chronic cutaneous lesions are esthetically prejudicial. There have been several case reports on thalidomide efficacy but long-term outcome is unknown. We report results in 10 cases of cutaneous sarcoidosis treated with thalidomide.PATIENTS AND METHODS: Data from ten patients with sarcoidosis treated with thalidomide between January 1998 and March 1999 were collected from delivery authorizations and analyzed. All ten patients had chronic cutaneous sarcoidosis resistant to conventional therapy. Six patients had an associated visceral localization and disease duration of 2 to 18 years (median 6 years). We considered that regression was complete when erythema and infiltration had totally disappeared, that regression was incomplete when cutaneous signs remained, and that treatment had failed when no effect was observed or when the disease worsened.RESULTS: Disease regression was noted in 7 patients for a daily dose of 1.84 mg/kg for 2.8 months. Skin lesions totally regressed in 3 patients, an incompletely in 4. Treatment failed in 3 patients. Patients were treated for 10 months (2 to 21 months). The daily dose of thalidomide was gradually reduced in 5 of 7 patients for whom treatment was effective. Three of these 5 patients relapsed and thalidomide was again given and was effective again at the same dose and after the same delay. We observed improved kidney function in one patient, improvement in nasal infiltration in one other and complete regression in 3 patients who achieved long lasting reduction in angiotensin convertase level. When treatment failed, the daily dose was 1.15 mg/kg and the treatment had to be stopped for 2 patients. Side effects were minor, excepting 2 cases of neuropathy.DISCUSSION: This open study of 10 patients treated with thalidomide showed the efficacy of a 1.84 mg/kg daily dose in 7 out of 10, but complete regression of the lesions was obtained in only 3 patients. Thalidomiide appears to suspend the disease, with relapse when the drug is discontinued and efficacy at re-introduction. This would argue against a placebo effect. The mode of action could involve immunomodulating and antiinflammatory mechanisms.     

Sarcoidosis associated with pegylated interferon alfa and ribavirin treatment for chronic hepatitis C: a case report and review of the literature

BACKGROUND: At least 2.7 million Americans are infected with chronic hepatitis C. An increasing number are treated with interferon alfa plus ribavirin regimens. Not surprisingly, this immune stimulation is associated with the development of autoimmune and cutaneous diseases. Several cases of sarcoidosis have been reported with hepatitis C treatment, most recently in association with pegylated interferon alfa plus ribavirin. Systemic manifestations of sarcoidosis are usually treated with oral steroids, which unfortunately often increase the hepatitis C viral load. Thus, it is important to ascertain whether systemic corticosteroids are required to treat interferon alfa-associated sarcoidosis. OBSERVATIONS: We report the third case of cutaneous sarcoidosis in association with pegylated interferon alfa plus ribavirin treatment. Our patient had both cutaneous and pulmonary involvement, which has been spontaneously resolving since his treatment regimen was completed. In addition, we review the 12 previously reported cases of cutaneous sarcoidosis that occurred in patients undergoing hepatitis C treatment with interferon alfa. CONCLUSIONS: As the number of patients being treated with interferon alfa and ribavirin for hepatitis C increases, it is essential that dermatologists recognize the association of this treatment with sarcoidosis, because skin lesions may provide the first clue to diagnosis. Development of sarcoidosis may relate to hepatitis C as a possible antigenic trigger in the presence of an enhanced helper T cells type 1 response from treatment. Sarcoidosis with skin lesions in patients undergoing hepatitis C treatment often follows a benign course, and interferon alfa therapy may sometimes be continued with resolution of sarcoidosis occurring spontaneously or within a few months of completing treatment. Cautious use of systemic corticosteroids is warranted given their adverse effects on hepatitis C viral loads.     

发生于特瑞普利单抗长期治疗后的大疱性类天疱疮二例

例1女,63岁,全身皮疹2个月伴瘙痒,表现为红斑基础上水疱大疱。2年前因直肠肛管恶性黑素瘤行肠周淋巴结清扫术,静脉注射特瑞普利单抗预防性治疗1年,停药后2周出现全身皮疹。上肢红斑处皮损直接免疫荧光示,IgG沿基底膜带沉积;血清盐裂间接免疫荧光,IgG沿表皮侧线状沉积。血清酶联免疫吸附试验示,BP180 > 200 U/...     

A comparative trial of single dose chemotherapy in paucibacillary leprosy patients with two to three skin lesions

A multicentric, double-blind, controlled, clinical trial was carried out to compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg (ROM) administered as single dose with that of standard WHO/MDT/PB six months regimen. The study subjects were 236 previously untreated, smear-negative patients, without nerve trunk involvement and having only two or three skin lesions. Randomization was done on individual patient basis. Results were analyzed for mean clinical score for improvement, marked clinical improvement and complete clinical cure at the time of release from treatment and at 12 months and 18 months of follow-up. Clinical improvement was seen in most patients in both regimens. Marked improvement (i.e., more than 90% reduction in clinical score) at 18 months was seen in 46.2% and 53.4% of the patients treated with ROM and standard regimens, respectively. But, significant difference in favour of standard PB regimen was seen in patients with three skin lesions and in patients in whom more than one body part was affected. Reversal reaction and adverse drug reactions were minimal in both groups.     

Cutaneous lupus erythematosus-treatment with pulsed dye laser

Because of its vascular selectivity, the flashlamp-pumped pulsed dye laser (585 nm) is efficacious in the treatment of vascular lesions and is successfully used for the treatment of port-wine stains and haemangiomas in children. Based on the encouraging results with these cutaneous vascular disorders, the cutaneous lesions of patients with lupus erythematosus (LE) have now also been treated with the pulsed dye laser. Cutaneous lesions in lupus erythematosus are often difficult to treat with readily available local therapeutic methods. We report here on a group of 12 patients whose LE lesions were treated with the pulsed dye laser. In 10 patients, the LE was limited to the skin, while two patients had systemic LE (SLE). Even in the two patients with SLE, a significant improvement of skin lesions was achieved. After a mean number of 51 laser sessions, a median clearance rate of 70% was attained for nine patients. In one case, the laser treatment failed to clear the lesions. Two patients did not show any visible improvement of the lesions, but pain and itching were significantly reduced. There were few side-effects. No prolonged laser-induced scarring occurred and in only two patients was hyperpigmentation seen, which had resolved completely after 4 and 5 months, respectively. During a median follow-up of 7 months (range: 3-32 months), only one patient (after a complete clearance of the skin lesions) had a small relapse. In summary, the pulsed dye laser is an effective therapy for the treatment of superficial skin lesions in LE.     

Comparative analysis of adverse drug reactions to tetracyclines: results of a French national survey and review of the literature

Summary Background The question of quantitative and qualitative differences between adverse drug reactions (ADRs) to tetracyclines was raised many years ago, especially for minocycline and doxycycline. Objectives To assess and compare ADRs related to tetracyclines according to sales figures in France through a national survey. Methods ADR data were collected from the French Pharmacovigilance Database (FPD), marketing authorization holders (MAH) and the literature. Sales analyses were based on MAH data provided annually to the French Drugs Agency. Results Among the tetracyclines available in France, doxycycline and minocycline are the most frequently used. However, their sales decreased between 1995 and 2007, more sharply for minocycline than doxycycline. According to the FPD, based on MAH data and published reports, minocycline‐associated ADRs were more serious and were reported more frequently than for the other tetracyclines. Minocycline and doxycycline ADR patterns differed: gastrointestinal disorders (especially oesophageal lesions) predominated with doxycycline, while intracranial hypertension and hepatic disorders were primarily reported with minocycline. Autoimmune disorders, drug reaction with eosinophilia and systemic symptoms (DRESS) and other hypersensitivity reactions were also more frequent with minocycline. ADRs reported with lymecycline and metacycline were essentially cutaneous and gastrointestinal disorders. Conclusions In the absence of markedly better efficacy against the various indications for tetracyclines, the minocycline benefit/risk ratio was clearly lower than that of doxycycline, and possibly those of lymecycline and metacycline. In light of these findings, minocycline should no longer be considered first‐line therapy for inflammatory skin disorders, especially acne.     

Erfolgreiche Therapie einer Haut- und Lungensarkoidose mit Fumarsäureestern

A 61-year old female patient with cutaneous sarcoidosis was treated with fumaric acid esters (Fumaderm). After 12 months of therapy, lesions were markedly improved and treatment was discontinued. 18 months later, the cutaneous lesions recurred, angiotensin converting enzyme (ACE) serum levels were increased and a chest X-ray demonstrated pulmonary involvement. Therapy with fumaric acid esters was again started. The skin showed improvement after 2 months and completely cleared within 17 months, within 4 months ACE levels normalized, and within 10 months radiologic changes markedly resolved. This case demonstrates a possible role for fumaric acid esters not only in the treatment of cutaneous but also systemic sarcoidosis.     

Relevant diagnostic implications of the therapeutic challenge with antitubercular therapy in an unusual case of sarcoidosis mimicking lupus vulgaris

Cutaneous manifestations in sarcoidosis are seen in 25–35% of patients with systemic disease and may be the sole manifestation in few patients. It is known that isolated cutaneous sarcoidosis is a great mimicker and can be easily misdiagnosed as other granulomatous conditions especially lupus vulgaris in regions with high burden of tuberculosis (TB). Here we present a case with cutaneous sarcoidosis who was initially misdiagnosed and treated as bifocal lupus vulgaris with antitubercular therapy (ATT) for 6 months. This nonresponsiveness to therapy prompted us to investigate the patient further for other differentials, failing which a diagnosis of cutaneous sarcoidosis was made and the patient was treated with oral steroids and methotrexate with complete clearance of lesions after 14 weeks of therapy. Our case reemphasizes the value of therapeutic trial of ATT in diagnosis of cutaneous TB and highlights the remarkable clinical mimic of sarcoidosis with lupus vulgaris.     

Three cases of cutaneous sarcoidosis: search for bacterial agent by the 16S RNA gene analysis and treatment with antibiotics

BACKGROUND: The aetiology of sarcoidosis remains controversial. An infectious origin is often discussed, but only anti-inflammatory or immunosuppressive treatment is recommended. OBJECTIVES: To investigate the hypothesis of bacterial origin by treating cutaneous sarcoidosis with antibiotics. METHODS: Patients with chronic cutaneous sarcoidosis, unresponsive to the usual treatment and not requiring systemic corticotherapy, were given combined antibiotherapy for 6 months. Search for bacterial DNA by amplification and sequencing of the 16S ribosomal RNA gene in skin biopsies of lesions before and after antibiotherapy was done. RESULTS: Three patients received a combined treatment with clarithromycin 1 g/day and ciprofloxacin 1 g/day. No clinical changes occurred in 2 cases and transient worsening in 1. Amplification for bacterial DNA was positive in all skin biopsies. The sequencing of this DNA could not identify a unique bacterial species. CONCLUSION: No evident bacterial origin could be demonstrated; however, this approach should be extended to more patients.     

Total skin electron beam irradiation for cutaneous T-cell lymphoma (mycosis fungoides)

Forty patients with the cutaneous T-cell lymphoma (mycosis fungoides) were treated with total skin electron beam irradiation. The total follow-up period was up to 116 months (median 57.5 months). The patients were irradiated with a total dose of 35 Gy over 10 weeks, using the six-field technique. Ten of these patients had lymph node involvement and were subsequently treated with chemotherapy. After the initial electron irradiation complete remission of the skin lesions was obtained in 87.5% of the patients. Relapse of skin lesions occurred in 52% of the patients after 2-72 months (median 4 months). Second line therapy consisted primarily of topical nitrogen mustard. The overall survival rate at 5 years was 70%. Despite the side-effects this treatment was tolerated well by all patients.     

Papular sarcoidosis of the knees: a clue for the diagnosis of erythema nodosum-associated sarcoidosis

BACKGROUND: In recent years we have systematically explored the skin whenever sarcoidosis was suggested and we have observed with increasing frequency the presence of granulomatous cutaneous lesions of sarcoidosis involving the knees. OBJECTIVE: We sought to evaluate the specific cutaneous lesions of sarcoidosis involving the knees. METHODS: A total of 18 patients with biopsy-proven specific cutaneous sarcoidosis predominantly involving the knees were included in the study. Biopsy specimens were evaluated under polarized light. RESULTS: Of these cases, 4 corresponded to scar-sarcoidosis, 1 to plaque-type sarcoidosis, and 13 were an admixture of papules and minute scars frequently associated with erythema nodosum (papular sarcoidosis of the knees). Foreign particles were observed in 10 of 13 patients with papular sarcoidosis. CONCLUSION: Papular sarcoidosis of the knees can be considered a frequent form of cutaneous sarcoidosis, mainly observed in acute forms of the disease, and frequently associated with erythema nodosum.     

Skin uptake of Gallium 67 in cutaneous sarcoidosis

A patient is presented with cutaneous sarcoidosis of the scalp. Ga-67 was intensively taken up by the skin lesions. Systemic involvement of parotid glands and mediastinum was also demonstrated by Ga-67 scintigraphy. Prednisolone therapy reversed promptly the pathologic Ga-67 uptake. Ga-67 scintigraphy should be performed in all patients suffering from cutaneous sarcoidosis as being the most sensitive method to demonstrate systemic involvement.     

Long-term cefuroxime axetil in subacute cutaneous lupus erythematosus. A report of three cases

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) is a subset of lupus erythematosus characterized mainly by prominent photoaggravated cutaneous manifestations. Standard therapies for SCLE include topical or systemic steroids and antimalarial drugs. Both methods show limited efficacy in clearing cutaneous lesions and occasionally produce serious side effects. AIM: To assess the efficacy of cefuroxime axetil, an oral cephalosporin with antibacterial and immunosuppressive activity, in patients with SCLE. METHODS: Three patients with SCLE were treated with cefuroxime axetil at a daily dose of 500 mg for 30-60 days. RESULTS: In all patients complete clearing of skin lesions was achieved and no side effects were observed. CONCLUSION: We suggest that long-term cefuroxime axetil administration might be an alternative treatment for patients with SCLE skin lesions.     

抗p200类天疱疮7例临床及免疫血清学特征分析

【摘要】 目的 总结抗p200类天疱疮患者的临床和免疫血清学特征。方法 收集2015年1月至2021年10月在中国医学科学院皮肤病医院确诊为抗p200类天疱疮的患者资料，回顾性分析其临床和免疫血清学特征。结果 纳入7例抗p200类天疱疮患者，盐裂皮肤-间接免疫荧光实验显示，7例患者血清IgG抗体均结合于盐裂皮肤的真皮侧，以真皮提取物为底物的免疫印迹显示，在相对分子质量200 000蛋白处有条带。4例呈经典型大疱性类天疱疮样损害，2例初起呈湿疹样损害，1例类似线状IgA大疱性皮病。6例循环IgG抗体可识别层粘连蛋白γ1-C端重组蛋白。4例患者接受不同剂量系统糖皮质激素治疗，其中1例对高剂量系统糖皮质激素（相当于泼尼松1.4 mg·kg-1·d-1）治疗抵抗；2例对米诺环素、氨苯砜治疗反应好；1例失访。4例患者在随访平均22.5个月时达到完全缓解停药；2例在随访平均8个月时达到最小剂量治疗保持完全缓解。结论 抗p200类天疱疮临床表现多样，重组Lnγ1-C端可作为可靠的抗原底物用于检测抗p200类天疱疮患者自身抗体；部分患者最终可达到完全缓解并停药。     

Thalidomid in der Behandlung der kutanen und systemischen Sarkoidose

The clinical courses of two patients suffering from generalized or disseminated cutaneous sarcoidosis are described. Both were treated with thalidomide 2×100 mg/day, later 100 mg/day. After 8 to 12 months of treatment the skin and systemic lesions had resolved almost completely.     

鱼刺伤肉芽肿10例临床分析

回顾分析2019年1月至2020年5月我院10例鱼刺伤肉芽肿的临床资料及治疗效果。10例患者中,男3例,女7例,平均发病年龄49岁;3例从事与海产相关的厨师职业,5例有鱼类或海鲜刺伤史;1例有菜刀切伤史,1例有手部外伤史。皮损主要表现为上肢红斑、结节,伴破溃结痂。3例患者皮损局限于手部,其余患者皮损沿淋巴管播散。所有患者组织病理检查见上皮样肉芽肿或炎性细胞浸润的非特异性表现。所有患者菌落或皮损组织DNA检测海分枝杆菌qPCR阳性。对皮损局限于手部的3例患者给予米诺环素50 mg,每日2次,平均疗程（4.67±2.08）个月,均痊愈。对6例播散性患者给予利福平150~600 mg联合克拉霉素500 mg每日1次,1例失访,5例痊愈,平均疗程（4.80±1.48）个月。对1例肝功能异常播散性患者给予多西环素100 mg,每日2次,9个月治愈。     

Cutaneous sarcoidosis: Prognosis and treatment

The physician who has made a diagnosis of cutaneous sarcoidosis is faced with three basic questions: (1) Are there lesions in organs other than the skin? (2) Should the patient be given treatment? (3) What will the final outcome of the disease be?

Cutaneous sarcoidosis can be a great imitator of other skin diseases with a wide spectrum of clinical manifestations ranging from small asymptomatic cutaneous lesions that fade spontaneously without scarring, to widespread skin lesions and disease in many organ systems. The latter may be associated with severe symptoms such as pulmonary insufficiency or life-threatening biochemical abnormalities. Approximately two thirds of all patients recover completely or with a minimum of residual changes, while 2–5% of sarcoidosis patients die from the disease.^1,2

It is therefore of interest to review the literature that deals with the course and prognosis of sarcoidosis. It is also important to deal with the association of cutaneous sarcoidosis and other types of sarcoidosis in order to provide the dermatologist with a basis for his or her decision about whether treatment should, in fact, be instituted.     

Cutaneous sarcoidosis treated with levamisole.

16 patients with cutaneous sarcoidosis were treated intermittently over a period of 6 months with levamisole in an open study. The skin lesions cleared in 2 of 13 patients completing the course of treatment. Aggravation of the sarcoidosis was noted in 2 other patients after a few weeks of treatment. Tuberculin sensitivity did not increase during the treatment period. Dinitrochlorobenzene sensitivity increased in 5 patients but the lesions did not clear in any of these patients. It is concluded that levamisole is not useful in the treatment of cutaneous sarcoidosis.     

Psoralen plus ultraviolet-A-bath photochemotherapy as an adjunct treatment modality in cutaneous chronic graft versus host disease

BACKGROUND: Cutaneous chronic graft versus host disease (GVHD) is a severe complication following allogeneic stem cell (PBSCT) and bone marrow transplantation (BMT). Immunosuppressive therapy consists of prednisone, cyclosporine-A, azathioprine or mycophenolate mofetil (MMF). Treatment of patients refractory to immunosuppression represents a major problem. METHODS: We report six patients suffering from severe chronic GVHD of the skin who did not respond to immunosuppressive therapy or relapsed after reduction of glucocorticosteroids. Patients were treated with psoralen plus ultraviolet (PUVA)-bath photochemotherapy three times weekly following a standardized treatment protocol under continued treatment with prednisone and/or MMF. One patient was additionally pretreated with ultraviolet-A1 (UV-Al). RESULTS: After a median of 14, 5 treatment sessions, skin lesions improved. Out of six patients, three showed a complete remission. In all patients, systemic immunosuppressive therapy could be reduced. In sclerodermic lesions, skin thickness returned to the levels of normal skin after 25 treatments confirmed by 20 MHz ultrasound evaluation. In a follow-up ranging from 2 to 21 months (median 10, 3 months), skin conditions remained stable. CONCLUSION: Psoralen plus ultraviolet-A-bath represents an effective adjunct treatment option for extensive chronic and sclerodermic cutaneous GVHD offered by dermatologists. This is of high interest in patients suffering from cutaneous GVHD resistant to conventional immunosuppressive therapy and should be included to the menu of topical treatment options for chronic cutaneous GVHD.     

Cutaneous sarcoidosis with cardiac involvement.

Despite the clinical importance of cardiac involvement in the prognosis of sarcoidosis, it is often overlooked because of the subclinical disease progression and difficulty in diagnosis. We report here five patients with cutaneous sarcoidosis lesions where cardiac involvement was detected with the appearance of mild cardiac symptoms on a careful examination of the heart after cutaneous sarcoidosis was diagnosed. In four of the five cases, the patients had annular lesions while the fifth case showed a nodular eruption on the face. Three of the five patients showed complete AV block while one showed complete right bundle block and left bundle anterior branch block. All four patients with conduction disturbances underwent a permanent pacemaker implantation with prednisolone tapering therapy. The remaining patient had congestive heart failure and was treated with prednisolone alone. The present findings support the belief that sarcoidosis patients with cutaneous lesions, especially facial annular lesions, should be carefully examined and monitored for cardiac involvement, even in cases without apparent cardiac symptoms.