Studying the effect of adding growth factors to the autologous melanocyte keratinocyte suspension in segmental vitiligo

Addition of different growth factors to the medium used in autologous melanocyte‐keratinocyte transplantation procedure (MKTP) was reported in the literature. The aim of the current study was comparison of response to MKTP in segmental vitiligo (SV) with and without adding growth factors to the suspension medium. Eighteen cases with SV were randomly divided into two groups. In group A: Ham F12 medium was used for suspension and in group B: 5 ng/mL recombinant basic fibroblast growth factor (bFGF) and 25 mg/500 mL 3′5′ cyclic adenosine monophosphate (cAMP) were added to the medium. All cases received NB‐UVB twice weekly for 24 weeks. The area of vitiligo lesions was measured before and after therapy by point‐counting technique and complications were recorded. Excellent response (90%‐100% repigmentation) occurred in 5/9 cases (56%) in group A and 7/9 cases (78%) in group B (with growth factors). A significant decrease in the area of treated lesions before and after therapy was found in both groups A and B (P = .0012 and .0004, respectively), however, a higher percentage of reduction in area of vitiligo was seen in group B cases (70% in group A vs 90% in group B; P value: .028). Marginal halo was seen in five cases in group A and six in group B. In conclusion addition of bFGF and cAMP to MKTP medium improved the results of the procedure. It could be considered if economically feasible.     

Subacute cutaneous lupus erythematosus after immunotherapy for renal‐cell carcinoma: the case for interferon‐alpha

Subacute cutaneous lupus erythematosus (SCLE) is a photosensitive dermatosis characterized by papulosquamous or annular lesions. It can be caused by a variety of medications. We report a case of SCLE in a patient after interferon‐α treatment for metastatic renal‐cell carcinoma and discuss the potential role of interferons in the pathogenesis of CLE.     

Subacute cutaneous lupus erythematosus presenting as poikiloderma

Subacute cutaneous lupus erythematosus (SCLE) is a recognised variant of lupus erythematosus (LE), which accounts for 10–15% of all cases of cutaneous LE, occurring most commonly in young to middle‐aged white women. Diagnosis is based on the detection of anti‐Ro/SS‐A antibodies in the skin and serum, characteristic clinical and histological cutaneous involvement, and relatively mild systemic involvement. Several unusual variants of SCLE have been reported including erythrodermic SCLE, SCLE with vitiligo‐like lesions, acral SCLE and bullous SCLE. Poikoilodermatous SCLE is a recognised but rare variant of SCLE. There are currently only two case reports, comprising five individual cases, in the literature. We present a case of SCLE in which the main clinical findings were an extensive photodistributed poikilodermatous rash and alopecia.     

Subacute cutaneous lupus erythematosus induced by terbinafine: case report and review of literature

Systemic lupus erythematosus and subacute cutaneous lupus erythematosus (SCLE) occasionally evolve as adverse reactions to a large variety of chemically different drugs. We here report on a 76‐year‐old woman who developed SCLE within 10 days after initiation of oral terbinafine. Analysis of the 27 cases of terbinafine‐induced SCLE in the literature revealed that this disorder has been reported 6 times more often in females than in males. Skin lesions evolved on average around 7 weeks after starting the drug. In 79% of the cases ANA could be detected while antibodies against Ro/SS‐A and La/SS‐B were found in 86% and 39%, respectively. Remarkably, anti‐histone antibodies were present in only 29%. In all cases terbinafine‐induced SCLE resolved after discontinuation of the triggering agent. Systemic treatment with anti‐malarials and/or corticosteroids does not appear to be mandatory.     

Drug-induced subacute cutaneous lupus erythematosus: a paradigm for bedside-to-bench patient-oriented translational clinical investigation

At least 71 patients have been reported in which their otherwise typical subacute cutaneous lupus erythematosus (SCLE) skin lesions were felt to have been temporally associated with the systemic administration of a drug. The mean age of this cohort of drug-induced SCLE (DI-SCLE) patients was 59 years of age which is somewhat older than the mean age of previously reported idiopathic SCLE patient cohorts. Patients had been taking the suspected triggering drug for weeks to years before the onset of SCLE skin lesions. In addition, it was not unusual for 2–3 months to be required for resolution of the SCLE skin lesions following discontinuation of the triggering drug. A relatively large number of drugs representing different pharmacological classes have been implicated in the induction of SCLE. The drug classes that were more frequently encountered were those used for the treatment of cardiovascular disease, especially hypertension. Calcium channel blockers were especially common in this regard. Elderly individuals being treated for hypertension are often taking multiple classes of drugs that have been implicated in triggering SCLE (thiazide diuretics, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, beta-blockers). An approach to the management of DI-SCLE is presented. Ro/SS-A autoantibodies tended to remain present in the blood after resolution of drug-induced SCLE skin lesions. A common link between the disparate group of drug structures implicated in triggering SCLE is their tendencies to produce photosensitivity and lichenoid drug reactions. This leads to the speculation that DI-SCLE could represent a photo-induced isomorphic/Köebner response in an immunogenetically predisposed host.     

Drug-induced subacute cutaneous lupus erythematosus: evidence for differences from its idiopathic counterpart

Background Drug‐induced subacute cutaneous lupus erythematosus (DI‐SCLE) is a lupus variant with predominant skin involvement temporally related to drug exposure and resolving after drug discontinuation. It usually presents with annular polycyclic or papulosquamous eruptions on sun‐exposed skin and shows serum anti‐Ro/SSA antibodies. Objectives To address the question whether DI‐SCLE differs significantly from idiopathic SCLE by virtue of clinical features. Methods Ninety patients with SCLE seen in our departments from 2001 to 2010 were reviewed. Eleven of them diagnosed as having DI‐SCLE were evaluated for type of skin lesions, systemic involvement, clinical course, and histopathological, direct immunofluorescence and laboratory findings. The cutaneous features were compared with those of the 79 patients with idiopathic SCLE. Results The cutaneous picture was widespread in 82% of patients with DI‐SCLE and in 6% of those with idiopathic SCLE [odds ratio (OR) 66·6, 95% confidence interval (CI) 11·2–394·9; P = 0·0001]. Bullous and erythema multiforme (EM)‐like lesions were present in 45% of patients with DI‐SCLE and in 1% of those with idiopathic SCLE (OR 65·0, 95% CI 6·5–649·6; P = 0·0001). Vasculitic lesions were observed in 45% of patients with DI‐SCLE and in 3% of those with idiopathic SCLE (OR 32·1, 95% CI 5·1–201·7; P = 0·0001). Malar rash occurred in 45% of patients with DI‐SCLE and in 6% of those with idiopathic SCLE (OR 12·3, 95% CI 2·8–54·9; P = 0·001). Visceral manifestations were excluded in all patients with DI‐SCLE. Anti‐Ro/SSA antibodies were found in all but one patient with DI‐SCLE and disappeared after resolution in 73% of cases. Conclusions DI‐SCLE differs from idiopathic SCLE by virtue of distinctive cutaneous features, particularly the widespread presentation and the frequent occurrence of malar rash and bullous, EM‐like and vasculitic manifestations.     

Efficacy and safety of noncultured melanocyte‐keratinocyte transplant procedure for vitiligo and other leukodermas: a critical analysis of the evidence

Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte‐keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001–2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in‐depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.     

Failure of physiologic doses of pure UVA or UVB to induce lesions in photosensitive cutaneous lupus erythematosus: implications for phototesting

BACKGROUND: Phototesting studies in cutaneous lupus erythematosus have yielded variable results, with most trials reporting photo-induction of lesions by both UVA and UVB in substantial numbers of patients. OBJECTIVES: To determine the minimal erythema dose in patients with subacute cutaneous lupus erythematosus (SCLE) and controls. PATIENTS/METHODS: We phototested nine patients with SCLE and 14 skin type-matched controls, using repetitive dosing of UVA1 and UVB, but with filters that removed most of the shorter UVC and longer infrared and visible light. In addition, DNA was isolated from anticoagulated blood to genotype the TNF-alpha 308 region in each patient and control. RESULTS: We were unable to demonstrate a difference in minimal erythema dose (MED) between patients and controls, or any correlation of MED with either TNF genotype or systemic drug therapy for SCLE. In addition, no SCLE skin lesions were induced in the nine patients with either UVA or UVB, and one patient cleared a skin lesion after low-dose UVA1 irradiation. CONCLUSIONS: The potential role of wavelengths outside the UVA and UVB range in the photo-induction of cutaneous lupus skin lesions needs to be investigated, and there is a need to standardize phototesting equipment and procedures for patients with cutaneous lupus erythematous.     

Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients

Background Lupus erythematosus (LE) is a chronic, autoimmune disease resulting from an interaction of genetic, environmental and hormonal factors and characterized by a spectrum of clinical forms with variable evolution from a localized cutaneous form to a life‐threatening systemic form. Objective To analyse and compare the prevalence and characteristics of the main clinical and immunological manifestations of subacute cutaneous LE (SCLE) and chronic CLE (CCLE). Methods A total of 270 patients with CLE (112 patients with SCLE and 158 patients with CCLE) were studied retrospectively. The clinical and serological characteristics of all the patients were collected in a chart review. Results The patients with SCLE had a higher prevalence of annular and papulosquamous lesions, Raynaud phenomenon, mucous membrane ulcers, malar rashes, photosensitivity, vasculitis and a lower frequency of discoid lesions and alopecia compared with patients with CCLE. Patients with SCLE had a higher prevalence of arthralgias (P < 0·001), xerophthalmia (P = 0·045), arthritis (P < 0·001), nephropathy (P = 0·003) and systemic LE (SLE) (P < 0·001) compared with patients with CCLE. Patients with SCLE also had a higher frequency of laboratory and serological abnormalities than patients with CCLE. Generalized discoid LE (DLE) was associated with a higher prevalence of photosensitivity (P < 0·001), panniculitis (P = 0·009) and SLE (P = 0·003) than localized DLE. In patients with SCLE and those with CCLE, photosensitivity, arthralgias, arthritis, nephropathy and xerophthalmia were associated with SLE. In patients with SCLE, significant correlations existed between clinical and immunological data. Conclusions In our series, differences in the expression of CCLE and SCLE were found with respect to the distribution and type of lesions, systemic features and immunological findings.     

Subacute cutaneous lupus erythematosus presenting as erythroderma

Erythrodema secondary to subacute cutaneous lupus erythematosus (SCLE) is rare. We report a 61-year-old man presenting with erythroderma secondary to SCLE. During erythrodermic phase our patient still had few annular and polycyclic lesions characteristic of SCLE. He was successfully treated with topical and oral corticosteriods.     

Toxic epidermal necrolysis‐like subacute cutaneous lupus erythematosus

Toxic epidermal necrolysis (TEN)‐like presentations have been described in non–drug‐induced settings. We describe a case of subacute cutaneous lupus erythematosus (SCLE) in a 53‐year old woman, which evolved into a TEN‐like presentation over the course of 4 weeks. The patient responded rapidly to treatment with intravenous methylprednisolone. This article draws attention to features that may be used to differentiate classical TEN from TEN‐like SCLE.     

Relationship between circulating anti-Ro/SS-A antibody levels and skin disease activity in subacute cutaneous lupus erythematosus

Anti-Ro/SS-A antibody levels in 80 serum specimens from 12 patients with subacute cutaneous lupus erythematosus (SCLE) were determined by immunodiffusion and enzyme-linked immunosorbent assay in order to examine the changes in this autoantibody response with time and to study the relationship between levels of this antibody and SCLE skin disease activity. Anti-Ro/SS-A antibody levels were found to vary considerably over time in a given patient when measured by both assays. Several patients who did not have detectable levels of this antibody at the time of their initial examination were found to be antibody positive at follow-up examinations. However, no significant relationship was found between antibody levels in either assay and SCLE skin disease activity. While not ruling out a pathogenetic role for this antibody in the elicitation of SCLE skin lesions, these results would suggest that other factors are likely to be involved.     

Refractory subacute cutaneous lupus erythematosus successfully treated with rituximab

A 48-year-old woman presented with pruritic, scaly, annular plaques over her upper back and chest that were clinically, serologically and histologically characteristic of subacute cutaneous lupus erythematosus (SCLE). She failed to respond to conventional treatment, which included high-dose hydroxychloroquine, methotrexate, prednisolone, chloroquine, acitretin, thalidomide, dapsone and azathioprine. Subsequently treated with intravenous rituximab 375 mg/m² weekly for 4 weeks, she remained on adjuvant oral hydrochloroquine 600 mg daily and topical clobetasol propionate 0.05% ointment as required. Clearing of annular plaques was noted 8 weeks after the initial course of rituximab. By 12 weeks there were no new lesions and only post-inflammatory hyperpigmentation remained. Both hyper- and hypopigmentation, which is more common, are consistent with SCLE lesion regression. Skin lesions recurred 11 months later; however, no further lesions occurred after re-introduction of rituximab therapy. The treatment was well tolerated. A maintenance regimen of rituximab, 375 mg/m² every 8 weeks for 2 years, was commenced 3 months after completing the second course of treatment, with ongoing disease remission. Rituximab appears to have activity in refractory SCLE and clinical trials are required to further assess this potential therapy.     

Mycophenolate sodium for subacute cutaneous lupus erythematosus resistant to standard therapy

Background Approximately 75–95% of patients with cutaneous lupus erythematosus respond to antimalarial therapy and/or topical glucocorticosteroids. Immunosuppressive agents are usually considered a second‐line approach in patients with resistant disease. Objectives This was a prospective, nonrandomized, open pilot study to evaluate the efficacy of mycophenolate sodium monotherapy in patients with recalcitrant subacute cutaneous lupus erythematosus (SCLE). Methods Monotherapy with oral enteric‐coated mycophenolate sodium 1440 mg daily was given for a total of 3 months. Treatment outcome was evaluated by means of a validated clinical score for cutaneous lupus erythematosus, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), as well as 20‐MHz ultrasound measurements and colorimetry. Safety assessment included the monitoring of adverse effects and clinical laboratory parameters. Results Ten patients with active SCLE resistant to at least one standard therapy were included in the trial. Mycophenolate sodium led to a remarkable improvement of skin lesions, resulting in a significant decrease of the mean ± SD CLASI from 10·8 ± 6·0 at the beginning to 2·9 ± 2·6 at the end of therapy. Clinical improvement was confirmed by ultrasonographic assessments and colorimetry. No serious side‐effects were noted. Conclusions Mycophenolate sodium is beneficial and safe in the treatment of patients with SCLE that failed standard therapy. However, these preliminary data must be confirmed by randomized controlled trials including a larger sample size.     

Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. Some case reports and pilot studies have suggested efficacy against systemic lupus erythematosus (LE), particularly in the case of lupus nephritis. Reports on MMF treatment of skin manifestations of LE are still anecdotal. We report two cases with extensive skin lesions owing to subacute cutaneous LE (SCLE). Both patients had been treated with azathioprine and antimalarials without effect. Finally both patients were given highly dosed glucocorticosteroids, which were also ineffective but led to vertebral fractures because of long-term steroid treatment in one patient and steroid-induced psychosis in the other. MMF 2 g daily caused the skin manifestations to disappear within a few weeks in both patients. One patient was followed up for more than 24 months, and showed good toleration of MMF treatment. The skin remained stable over this period when at least 1 g MMF per day was administered. In conclusion, MMF appears to be an attractive treatment option in skin manifestations of SCLE, and seems to be beneficial for patients with steroid-refractory lesions that are also resistant to treatment with immunosuppressants or antimalarials. The observations suggest that further evaluation of this route in randomized controlled trials is warranted.     

A CASE OF SUBACUTE CUTANEOUS LUPUS ERYTHEMATOSUS WITH A HIGH TITER OF RNP ANTIBODY

A 30-year-old man developed severe erosive lesions in his oral cavity and transient Raynaud's phenomenon followed by discoid lupus erythematosus (DLE)-like lesions and non-scarring erythema. He had a high titer of RNP antibody as well. Widespread DLE (w-DLE), subacute cutaneous lupus erythematosus (SCLE) and mixed connective tissue disease (MCTD) were suspected as his condition. Finally we diagnosed him as having SCLE accompanied with a high titer of RNP antibody.     

ITP as an initial manifestation of subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) is an entity characterized by widespread polycyclic lesions that heal without scarring. Skin lesions with marked ultraviolet sensitivity are distributed in an annular and/or psoriasiform configuration. Idiopathic thrombocytopenic purpura, which is an autoimmune disease (ITP), is mediated by a destructive immunoglobulin G antibody response to the platelets' membrane components. We report a case of subacute cutaneous lupus erythematosus initially manifested as thrombocytopenia, which was diagnosed as idiopathic thrombocytopenic purpura (ITP) and treated with splenectomy. Seven months later, development of cutaneous involvement followed the diagnosis of ITP. The clinical and histological features of the lesions were compatible with SCLE. Serological evaluations showed a negative anti-nuclear antibody test and an elevated anti-SSB/La antibody level. Symptoms for systemic involvement were negative. Although the clinical features such as photosensitivity, discoid rash, and thrombocytopenia were in favor of SLE, the patient did not fulfill the criteria of the American Rheumatism Association (ARA) for SLE.     

Thalidomide in the treatment of refractory cutaneous lupus erythematosus: prognostic factors of clinical outcome

Background Although thalidomide has been shown to be effective in patients with refractory cutaneous lupus erythematosus (CLE), its use is still hampered by its potential severe side‐effects and the current restricted availability. Objectives To evaluate prospectively the clinical efficacy and safety of low‐dose thalidomide in an observational study and to establish prognostic factors of clinical outcome. Methods Sixty consecutive patients with refractory CLE were treated with thalidomide (100 mg daily). Clinical response was assessed by the CLE Disease Area and Severity Index (CLASI). Clinical and immunological parameters were evaluated during treatment. Results Patients were followed for up to 8 years (range 2–18). One patient discontinued treatment because of side‐effects. Of the 59 remaining patients, 58 (98%) achieved clinical response, already noticeable at 2 weeks following treatment. Complete response occurred in 50 patients (85%). Clinical relapse was frequent (70%) and usually occurred 5 months after withdrawal or reduction of thalidomide. Subacute CLE (SCLE) was the predicting factor of long‐term remission after therapy discontinuation [odds ratio (OR) 30, 95% confidence interval (CI) 5·82–154·63], whereas discoid lupus erythematosus (DLE) was predictive of relapse (OR 5·71, 95% CI 1·36–24·06). Eleven patients (18%) reported paraesthesia; in five of the 11, nerve conduction studies confirmed a sensory polyneuropathy. Neurological symptoms resolved in 12 months (range 6–18) after thalidomide withdrawal. Two patients, heavy smokers and without antiphospholipid antibodies, had a cerebral ischaemic event. Conclusions Low‐dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long‐term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.     

Oral lesions in four cases of subacute cutaneous lupus erythematosus

Patients with subacute cutaneous lupus erythematosus (SCLE) present with intense photosensitivity. Clinical patterns comprise papulosquamous or annular lesions on sun-exposed areas; although the face is usually spared. Intraoral lesions have not been reported in most case series of SCLE, but are well-documented in other forms of lupus erythematosus. This study included four female patients diagnosed with SCLE, who presented with specific oral involvement consisting of palatal patches (three cases), buccal mucosal patches (one case), gingival keratotic erythema (one case), and lip lesions (one case). All patients presented with exuberant facial lesions, a condition not often observed in SCLE. Our findings suggest that oral involvement in SCLE may not be as rare as once thought, and that patients with intense facial lesions are at particular risk of developing oral lesions.     

Measuring the activity of the disease in patients with cutaneous lupus erythematosus

The Systemic Lupus Activity Measure (SLAM) is a system proposed by rheumatologists to measure disease activity in their patients with systemic lupus erythematosus (LE). It involves scoring a group of clinical symptoms and laboratory findings, the maximum possible score being 84. In systemic LE, the mid-point is between 9 and 12. We applied SLAM to 176 patients with cutaneous LE. Ninety-seven had localized discoid LE (L-DLE), 59 had disseminated discoid LE (D-DLE) and 20 had subacute cutaneous LE (SCLE). Eighty-five patients had low activity disease (0-4 points), 72 mildly active disease (5-9 points), 15 moderately active disease (10-14 points) and only four had very active disease (>/= 15 points). The most frequent lesions in patients who scored more than 10 points were photosensitivity, cicatricial alopecia, Raynaud's phenomenon and oral ulcers. Fifty patients were followed up for more than 5 years (mean follow-up 9 years). Nine of these had an increased SLAM score. Seven had L-DLE, one D-DLE and one SCLE. Seven of the 50 patients had photosensitivity, five cicatricial alopecia, five non-cicatricial alopecia, two Raynaud's phenomenon and two oral ulcers. Three patients who started with L-DLE evolved to D-DLE. The SLAM system is useful in the monitoring of disease activity in patients with cutaneous LE. Over time, even L-DLE patients may develop active disease. Photosensitivity, alopecia, oral ulcers and Raynaud's phenomenon seem to herald a worse prognosis.