tacrolimus and Lupus-Erythematosus--Cutaneous

Topical tacrolimus and pimecrolimus are indicated for treatment of atopic dermatitis, but they have been studied in many off-label uses. Double-blind and open studies have shown favorable results with topical tacrolimus and pimecrolimus in oral lichen planus. In 1 study of oral lichen planus, blood tacrolimus was detected in 54% of patients, but there were no signs of systemic toxicity. Double-blind and open studies of vitiligo have shown favorable results with tacrolimus in combination with excimer laser, especially for lesions over bony prominences and on extremities. Similarly, double-blind studies of vitiligo have shown favorable results when pimecrolimus is combined with narrow-band UVB, especially for facial lesions. Double-blind and open studies of psoriasis have shown favorable results for tacrolimus and pimecrolimus, especially for inverse psoriasis. Topical calcineurin inhibitors have been effective in many other cutaneous disorders, and further studies would help clarify their roles.

Topics: Administration, Cutaneous; Calcineurin Inhibitors; Child; Child, Preschool; Crohn Disease; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Female; Humans; Lichen Planus, Oral; Lupus Erythematosus, Cutaneous; Male; Off-Label Use; Psoriasis; Rosacea; Skin Diseases; Tacrolimus; Therapies, Investigational; Vitiligo

Lesions of cutaneous lupus erythematosus (CLE) are refractory to a wide range of topical or systemic therapies. The pathogenesis of CLE is multifactorial and polygenic, and many of its details remain unclear. However, immunologic evidence suggests the possible therapeutic use of tacrolimus and pimecrolimus. CLE is one of the most common dermatological autoimmune disorders worldwide, which includes systemic lupus erythematosus (SLE) with malar rash, subacute cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE).. Our aim was to determine the efficacy of topical pimecrolimus and tacrolimus in the treatment of cutaneous lupus erythematosus.. The literature was systematically reviewed. Medline, Embase, and the Cochrane Database were searched for systemic reviews, randomised controlled trials and nonrandomised clinical trials using the search terms "pimecrolimus", "Elidel", "SDZ ASM 981", "tacrolimus", "Protopic", "FK506" and "cutaneous lupus erythematosus". Studies were assessed independently by two authors.. Five studies were eligible for inclusion in this review. Only one of them was a randomised controlled trial (RCT). There was no significant difference between tacrolimus and clobetasol; however, evidence indicates the highest tolerability of tacrolimus compared with corticosteroids. This review indicates the efficacy of tacrolimus and pimecrolimus in, at least initial, cutaneous lesions of SLE. However, in SCLE and DLE lesions, the efficacy appears to be lower, perhaps due to the chronicity of those lesions.. The lack of RCTs is characteristic. Future studies should focus on efficacy, short- and long-term effects and cost-effectiveness. However, tacrolimus and pimecrolimus show efficacy, and such effort is worthwhile.

Topics: Administration, Topical; Clobetasol; Databases, Factual; Glucocorticoids; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Randomized Controlled Trials as Topic; Skin; Tacrolimus

This literature review revealed an unexpected paucity of data derived from adequately powered, randomized, controlled trials to guide evidence-based treatment of the cutaneous manifestations of lupus. Lupus erythematosus is characterized by spontaneous fluctuations in disease activity. This characteristic may serve to explain some of the contradictions in published evidence and cautions us not to rely too heavily on data derived from inadequately powered studies, small uncontrolled case series, or individual case reports, which are additionally subject to publication bias. Clearly, there is a pressing need to conduct adequately powered clinical research studies to fill these gaps in our knowledge. There also is a need for controlled trials to assess drug safety in patients with SLE. Much of the data regarding side-effect profiles of the immunomodulatory drugs has been compiled in patients receiving organ transplantation or chemotherapy for malignant diseases and extrapolated to patients with lupus. Given that there is often a substantial overlap in symptoms related to drug toxicity and to lupus erythematosus, careful studies should be conducted to assess the safety and toxicities of both established and newer medical therapies, especially those whose efficacy is supported only by small trials and case reports. Table 4 summarizes the results of our literature review. For each drug, we give the highest level of data we found, both for the treatment of lupus erythematosus in general and for the treatment of the cutaneous manifestation of lupus in particular.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antimalarials; Azathioprine; Cladribine; Cyclophosphamide; Cyclosporine; Evidence-Based Medicine; Humans; Immunoglobulin G; Immunologic Factors; Immunotherapy; Isoxazoles; Leflunomide; Lupus Erythematosus, Cutaneous; Methotrexate; Mycophenolic Acid; Rituximab; Tacrolimus; Thalidomide

Topical calcineurin inhibitors are licensed for the treatment of atopic dermatitis; however, the efficacy of tacrolimus in cutaneous lupus erythematosus (CLE) has only been shown in single case reports.. In a multicenter, randomized, double-blind, vehicle-controlled trial, we sought to evaluate the efficacy of tacrolimus 0.1% ointment for skin lesions in CLE.. Thirty patients (18 female, 12 male) with different subtypes of CLE were included, and two selected skin lesions in each patient were treated either with tacrolimus 0.1% ointment or vehicle twice daily for 12 weeks. The evaluation included scoring of clinical features, such as erythema, hypertrophy/desquamation, edema, and dysesthesia.. Significant improvement (P < .05) was seen in skin lesions of CLE patients treated with tacrolimus 0.1% ointment after 28 and 56 days, but not after 84 days, compared with skin lesions treated with vehicle. Edema responded most rapidly to tacrolimus 0.1% ointment and the effect was significant (P < .001) in comparison to treatment with vehicle after 28 days. Clinical score changes in erythema also showed remarkable improvement (P < .05) after 28 days, but not after 56 and 84 days. Moreover, patients with lupus erythematosus tumidus revealed the highest degree of improvement. None of the patients with CLE demonstrated any major side effects.. The study was limited by the small sample size.. Explorative subgroup analyses revealed that topical application of tacrolimus 0.1% ointment may provide at least temporary benefit, especially in acute, edematous, non-hyperkeratotic lesions of CLE patients, suggesting that calcineurin inhibitors may represent an alternative treatment for the various disease subtypes.

Topics: Administration, Topical; Adult; Age Factors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Hospitals, University; Humans; Lupus Erythematosus, Cutaneous; Male; Maximum Tolerated Dose; Middle Aged; Ointments; Recurrence; Reference Values; Risk Assessment; Severity of Illness Index; Sex Factors; Tacrolimus; Treatment Outcome

Topics: Adult; Clobetasol; Double-Blind Method; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Male; Ointments; Tacrolimus; Treatment Outcome

To determine the efficacy of tacrolimus ointment 0.1% on resistant cutaneous lesions in patients with lupus erythematosus.. Twelve patients with skin manifestations were studied. Six had discoid lupus (DL), four subacute cutaneous lupus erythematosus (SCLE) and two systemic lupus erythematosus (SLE). All patients had extensive skin lesions refractory to previous treatment. Patients received topical tacrolimus 0.1% for a minimum of 6 weeks and response was evaluated by physicians' and patients' assessment and documented with photographs at baseline and at the end of the treatment.. Eleven of 12 patients completed the therapy. One patient with DL discontinued because of side--effects-peeling and a burning sensation. Six patients were clearly improved, one patient had a minor remission of his face lesion while in four the rashes remained the same. Two patients with SCLE had significant regression of their lesions while the other two had no improvement. In DL, two had certain improvement, one minor improvement and two were without response. The patients with SLE had significant amelioration of their extensive photosensitive rash.. Tacrolimus ointment 0.1% may be an effective alternative in patients with severe resistant cutaneous manifestations in lupus erythematosus.

Topics: Adult; Aged; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Ointments; Tacrolimus; Treatment Outcome

Topical treatment of cutaneous lupus erythematosus usually includes potent glucocorticosteroids. However, prolonged use causes adverse side effects including skin atrophy as the foremost concern. In contrast to glucocorticosteroids, the anti-inflammatory and immunosuppressive macrolactam pimecrolimus has no atrophogenic potential. Affected areas of 11 patients with different forms of lupus erythematosus were treated with pimecrolimus 1% cream under semiocclusive conditions twice daily for 3 weeks. Skin involvement before and after therapy was assessed by means of a clinical score. In all patients, significant regression of skin lesions was observed after therapy (P <.001). This was an open and uncontrolled study on a limited number of cases. We suggest that pimecrolimus 1% cream could be an efficacious and safe treatment option for cutaneous lupus erythematosus.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Child; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Patient Acceptance of Health Care; Tacrolimus; Treatment Outcome

Lupus erythematosus tumidus (LET) is an uncommon type of cutaneous lupus erythematosus (CLE) that is rarely associated with other forms of lupus erythematosus.. We report a 62-year-old Chinese man presented with recurrent erythematous facial plaques for 1 year and a low-grade fever for 1 week. He had been diagnosed as discoid lupus erythematosus (DLE) 1 year before. Physical examination showed diverse lesions, including prominent swelling of the eyelids, a few erythematous, edematous plaques on the left forehead, face, and neck, and 2 hairless macules. The histopathologic findings reveal liquefaction degeneration of the basal cells, perivascular, and periadnexal infiltration of lymphocytes, and interstitial mucin deposition in the superficial, and deep dermis.. A diagnosis of LET was made on clinical and histological features.. The patient started treatment with prednisolone (1 mg/kg. d), combined with hydroxychloroquine (200 mg twice daily), and topical tacrolimus.. The cutaneous lesions completely cleared after a period of 3 months. No adverse effects or clinical evidence of recurrence had been found during the 6-month follow-up period.. We report a case of LET converted from DLE with diverse lesions, unusual pathologic findings and slow response to the treatment of corticosteroids combined with hydroxychloroquine. We speculate that a continuous spectrum may include DLE, LET, and systemic lupus erythematosus (SLE), these 3 entities could potentially, convert between each other.

Topics: Antirheumatic Agents; Dermis; Drug Administration Routes; Drug Therapy, Combination; Humans; Hydroxychloroquine; Lupus Erythematosus, Cutaneous; Male; Middle Aged; Prednisolone; Tacrolimus; Treatment Outcome

Oral and topical calcineurin inhibitors (CIs) have been reported to lead to complete lesion remission in several dogs with vesicular cutaneous lupus erythematosus (VCLE).. To report retrospectively on the effectiveness and adverse effects of systemic (ciclosporin) and/or topical (tacrolimus/pimecrolimus) CIs in 11 dogs with VCLE.. Inclusion criteria were: (i) presence of characteristic annular, polycyclic or serpiginous ulcerations distributed over the groin, axillae and/or ventral abdomen; (ii) a histopathological diagnosis of VCLE (i.e. a lymphocyte-rich interface dermatitis with vesiculation); (iii) treatment that included CIs for at least eight weeks; and (iv) follow-up until death/euthanasia or for a minimum of 12 months post-diagnosis.. Initial therapy included the avoidance of excessive sun exposure, oral glucocorticoids [six of 11 dogs (55%); progressively tapered over a month] and once daily ciclosporin [11 dogs (100%); median 5.8 mg/kg]. A complete remission (CR) of signs occurred between days 35 and 70 after starting CIs in eight dogs (73%); increasing ciclosporin dosage and adding topical tacrolimus induced a CR in two additional dogs (18%). Relapses were common when doses were tapered or discontinued. With the exception of three dogs that were euthanized, clinical signs were maintained in CR with oral ciclosporin (eight of eight dogs treated, 100%) or topical tacrolimus/pimecrolimus (four of eight dogs; 50%) with a median follow-up of 2.9 years.. These observations support CIs as the preferable therapeutic alternatives to long-term immunosuppression with oral glucocorticoids in dogs with VCLE.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Calcineurin Inhibitors; Cyclosporine; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Lupus Erythematosus, Cutaneous; Male; Skin; Tacrolimus; Treatment Outcome

Topics: Administration, Cutaneous; Administration, Oral; Adult; Biopsy, Needle; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunohistochemistry; Lupus Erythematosus, Cutaneous; Male; Mucinoses; Prednisolone; Rare Diseases; Severity of Illness Index; Tacrolimus; Treatment Outcome

Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable.. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline.. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline.. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Dog Diseases; Dogs; Drug Combinations; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Male; Niacinamide; Tacrolimus; Tetracycline; Vitamin B Complex

Lupus miliaris disseminatus faciei (LMDF) is a distinctive facial eruption of a debatable nosology, unknown etiology and spontaneously resolving course albeit with scarring. The aim of this study was to present the clinico-histopathological features, the rationale for treating and therapeutic response in patients with LMDF treated with different agents, and to attempt to clarify its nosology. Clinical details and demographic data of 29 biopsy-proven cases of LMDF were studied. Laboratory work up included complete blood count, erythrocyte sedimentation rate, tuberculin testing, chest X-ray, serum calcium levels and serum angiotensin-converting enzyme levels. Special stains like Ziehl-Neelsen, periodic acid Schiff and reticulin staining were used, and acid-fast bacilli culture was performed in each patient. The patients were treated with oral minocycline, dapsone, prednisolone and isotretinoin as monotherapeutic agents, or with a combination of oral dapsone plus prednisolone, and oral dapsone plus topical tacrolimus. Six patients had extrafacial lesions. Histological analysis revealed three different patterns: tuberculoid granuloma with central caseation necrosis in 20 patients; sarcoidal-like granuloma in six patients; and non-specific localized perifollicular lymphohistiocytic infiltrate in three patients. Nine out of 11 patients treated with minocycline did not respond, whereas dapsone and low dose prednisone alone or in combination produced good results. Topical tacrolimus with dapsone in seven patients yielded excellent results. Early and judicious use of medicines can clear this condition without scarring. LMDF should be accepted as a distinct entity. Facial idiopathic granulomas with regressive evolution (FIGURE), an acronym suggested is an apt, self-explanatory and easy term for LMDF, with no connotation of tubercular etiology.

Topics: Adult; Dapsone; Drug Therapy, Combination; Facial Dermatoses; Female; Humans; Lupus Erythematosus, Cutaneous; Male; Middle Aged; Prednisone; Tacrolimus; Treatment Outcome; Young Adult

Despite a range of available topical and systemic therapies, treatment of cutaneous lupus erythematosus (CLE) can be challenging. Objectives. To evaluate the efficacy of a specially formulated preparation of tacrolimus 0.3% in clobetasol propionate 0.05% ointment (TCPO) in the treatment of CLE.. Case notes of 13 patients with treatment-resistant CLE (11 discoid LE, 1 systemic LE and 1 subacute cutaneous LE) who had used twice-daily TCPO (TCPO group) were reviewed. These were compared with five similar patients with resistant CLE who had been given 0.1% tacrolimus ointment alone (TO group).. In the TCPO group (mean treatment duration 20 months, range 1-72), a good or excellent response was seen in five and six patients, respectively; one patient showed slight improvement. Telangiectasia and acne were observed in two patients. No systemic side-effects were noted. In the TO group (mean treatment duration 6 months, range 1-24), one patient showed good improvement and two showed slight improvement.. The results of our small retrospective study suggest that TCPO may be more effective than either 0.1% tacrolimus or clobetasol propionate 0.05% ointment monotherapy in the treatment of recalcitrant CLE. Randomized controlled trials are needed to confirm these preliminary findings.

Topics: Administration, Topical; Adult; Aged; Clobetasol; Cohort Studies; Dermatologic Agents; Drug Administration Schedule; Drug Combinations; Female; Humans; Lupus Erythematosus, Cutaneous; Male; Middle Aged; Retrospective Studies; Tacrolimus; Treatment Outcome; Young Adult

Topics: Administration, Cutaneous; Dermatologic Agents; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Middle Aged; Tacrolimus; Treatment Outcome

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Male; Pemphigoid, Bullous; Tacrolimus

Topics: Administration, Oral; Administration, Topical; Aged; Anti-Inflammatory Agents; Basement Membrane; Chloroquine; Drug Therapy, Combination; Epithelium; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Methylprednisolone; Photosensitivity Disorders; Skin; Tacrolimus

Topics: Administration, Topical; Adult; Facial Dermatoses; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Middle Aged; Sampling Studies; Severity of Illness Index; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Tacrolimus; Treatment Outcome

Subacute cutaneous lupus erythematosus is a subset of cutaneous lupus erythematosus with unique immunological and clinical features. The first series of patients found to have drug-induced subacute cutaneous lupus erythemotosus were secondary to hydrochlorothiazide. Since that time, several other drugs have been implicated in the induction of subacute cutaneous lupus erythemotosus. A 44-year-old woman presented with a 9-week history of a mildly pruritic, photosensitive rash that started on her chest. One month prior to her skin outbreak she was started on bupropion for mild depression. She was noted to have multiple annular erythematous plaques on her anterior chest, shoulders, back, arms and face. The patient was advised to stop the bupropion and to start topical tacrolimus, and was encouraged to apply a broad-spectrum sunscreen. Her skin completely cleared within 1 month of initiating this treatment regimen. This case is a unique example of bupropion-induced subacute cutaneous lupus erythemotosus. Our patient exemplifies the necessity of a complete medical history, including current medications, especially when subacute cutaneous lupus erythemotosus is suspected.

Topics: Adult; Antidepressive Agents, Second-Generation; Bupropion; Depression; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Sunscreening Agents; Tacrolimus; Treatment Outcome

Topics: Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Middle Aged; Ointments; Tacrolimus

Topics: Facial Dermatoses; Follow-Up Studies; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Male; Middle Aged; Ointments; Skin; Tacrolimus; Time Factors

The topical therapy of cutaneous lupus erythematosus (LE) consists mainly of corticosteroids which may lead to significant side effects when overused. We report the efficacy of topical tacrolimus as a therapeutic adjunct in 3 patients with cutaneous LE of the face. All patients, 1 with systemic LE and a malar rash, 1 with annular subacute cutaneous LE, the other with a papular variant of subacute cutaneous LE, experienced significant improvement following application of tacrolimus ointment. Treatment with topical tacrolimus was tolerated well without major side effects in all patients. The presented cases are in line with recent reports that topical tacrolimus may be effective in facial LE.

Topics: Administration, Cutaneous; Adult; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Middle Aged; Pilot Projects; Tacrolimus

Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Dermatologic Agents; Female; Humans; Lupus Erythematosus, Cutaneous; Tacrolimus