Annular Lichenoid Dermatitis (of Youth)

About 20 years after its first description, Annular Lichenoid Dermatitis of Youth (ALDY) is recognized as a distinctive lichenoid dermatosis with specific clinical and histological features. The disease occurs mostly in young persons all over the world, runs a chronic course, and has an obscure etiopathogenesis. Clinically, lesions consist of persistent, asymptomatic erythematous macules and round-oval annular patches with a red-violaceous non-scaling border and central hypopigmentation, mostly localized on the groin and flanks. Histology shows a peculiar lichenoid dermatitis characterized by irregular epidermal hyperplasia with an alternation of thinned and quadrangular rete ridges and a dense band-like lichenoid infiltrate of lymphocytes in the papillary dermis. Typically, there is infiltration of lymphocytes into the lower epidermal layers with massive necrosis/apoptosis of keratinocytes, which is limited to the tips of rete ridges. Dermal lymphocytes are usually CD3+, CD4+, while most of the intraepidermal T cells are CD8+. Analysis of TCR-γ-chain gene rearrangement displayed polyclonality in all cases examined. Differential diagnosis mainly includes morphea, mycosis fungoides, annular erythemas and inflammatory lesions of vitiligo. Topical corticosteroids and topical tacrolimus represent the most effective drugs for ALDY treatment.

Genital nodular scabies in Indonesian adolescent boy

<p class="abstract">Scabies is an infection caused by infestation and sensitization to the parasitic mite <em>Sarcoptes</em> <em>scabiei</em> <em>var</em>. <em>hominis</em>. World Health Organization (WHO) in 2017 declared that scabies was included as Neglected Tropical Diseases (NTD) and become a significant health concern in many developing countries. According to the Global Burden of Disease Study in 2015, Indonesia was the first place among 195 countries with the greatest scabies burden. Nodular scabies is an uncommon clinical variant in classical scabies cases, characterized by persistent pruritic nodules due to immune response against the mites and their products (eggs and scybala). This variant was occurring in about 7% of scabies patients. The incidence and prevalence of nodular scabies are still unknown. Nodular scabies is usually found in young children and affect the male genitalia, especially in the scrotum. The diagnosis of nodular scabies generally can be made clinically and supported by a history of receiving adequate anti-scabies treatment. Active infestation form or atypical manifestations of nodular scabies might be confused the diagnosis. Diagnostic tools such as dermoscopic and skin biopsy may aid in differentiating them. Histopathology features also can rule out the differential diagnosis. Corticosteroid (topical or injection) and topical inhibitor calcineurin (tacrolimus) was reported effective in treating nodular scabies. We reported an Indonesian adolescent boy who has been diagnosed with scabies complained of persistent pruritic nodules on his genital for several months despite adequate anti scabies therapy being given. Intralesional corticosteroid injection was the options treatment of this case due to the nodular lesion being resistant with topical corticosteroids, while topical tacrolimus is difficult to obtain in our region.</p>

Local immunosuppression in WZS-pig to rhesus monkey Descemet’s stripping automated endothelial keratoplasty: An innovative method to promote the survival of xeno-grafts

Corneal xenotransplantation is an effective solution for the shortage of human corneas. We investigated the feasibility and efficacy of different postoperative protocols on xeno-Descemet's stripping automated endothelial keratoplasty (DSAEK) grafts. Thirty rhesus monkeys were randomly divided into three groups: control group (C), only Descemet's membrane (DM) stripping; DSAEK 1 (D1) and DSAEK 2 (D2) groups, DM stripping followed by endothelial keratoplasty. Betamethasone 3.5 mg was subconjunctival injected in groups control and D1 postoperatively, while animals in group D2 were treated with topical 0.1% tacrolimus and topical steroids. All groups were evaluated by slit-lamp microscopy, anterior segment OCT and LSCM for at least nine months. A total of 24 monkeys (24 eyes) met the inclusion criteria. Nine months after DSAEK surgery, all xenografts showed good attachment, and most corneas were transparent. Graft rejection occurred in 25% of the cases in group D1 and 28.57% of those in group D2 (P > 0.05). The corneal endothelium density in the DSAEK groups was 2715.83±516.20/mm² (D1) and 2220.00 ± 565.13/mm² (D2) (P > 0.05). Xenogeneic corneal endothelial grafts can survive and function in rhesus monkey eyes for a long time with subconjunctival steroid or topical tacrolimus and steroid treatment.

TOPICAL TACROLIMUS 0.1% FOR TREATMENT OF CUTANEOUS MICROCYSTIC LYMPHATIC MALFORMATIONS

Microcystic lymphatic malformations as described in the international literature form a subgroup of low-flow congenital vascular malformations (VM) resulting from irregular embryological development. Microcystic lesions normally manifest as an accumulation of lymph- and blood-filled vesicles that, when externalized, cause skin maceration with consequent pain and potential infection resulting in the impairment of the patient's quality of life. There is no consensus on a standardized algorithm nor clear guidelines for successful treatment of this type of lymphatic malformation, and treatment options employed often result in ambivalent and transient outcomes with a high rate of recurrence. The topical formulation of tacrolimus is a well-known FDA-approved anti-T cell agent that was recently identified as a potent activator of ALK1, which is involved in several processes and functions including angiogenesis. We investigated if topical administration of tacrolimus may be an effective therapy for directly targeting cutaneous microcystic lymphatic malformations as a complement to systemic treatment. The study enrolled four patients with cutaneous microcystic lymphatic malformations: three male (ages: 13, 15, 18) and one female (age: 30). Two of the patients presented lesions on their backs, one patient on the left hand and one on the left lower limb. All four patients received treatment with topical tacrolimus 0.1% twice a day for 10 weeks on a previously selected area for application. Weekly clinical follow-ups were conducted along with close physician-patient contact. All patients displayed a satisfactory response after treatment. Lymphorrhea and bleeding were stopped in all cases and the esthetic aspect of lesions improved in two patients. To date, all patients presented no clinically significant changes to the size or extension of the lesion. Topical tacrolimus treatment is a promising and reasonable option for microcystic lymphatic malformations. Our results encourage further exploration in larger populations with the consideration that it is a safe and effective alternative or complementary therapy to systemic treatment.

Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model

Background: Uveitis is an infrequent disease which constitutes a major cause of ocular morbidity. Correct management is essential, being corticosteroids its cornerstone. In case of contraindication to corticosteroids or treatment failure, the use of topical tacrolimus (TAC) could be an alternative which has already demonstrated safety and effectiveness in other ocular pathologies. However, TAC eye drops are not marketed, thus their elaboration must be carried out in Hospital Pharmacy Departments (HPDs). Methods: 32 Sprague-Dawley rats were divided into 4 groups of 8 rats each: a) untreated healthy rats (Healthy); b) untreated Endotoxin-Induced Uveitis model-rats (EIU); c) EIU-rats treated with standard treatment of dexamethasone ophthalmic drops (DXM) and d) EIU-rats treated with TAC-hydroxypropyl-β-cyclodextrin eye drops previously developed by our group (TAC-HPβCD). The mRNA expression levels of IL-6, IL-8, MIP-1α and TNF-α, quantitative analysis of leucocytes in aqueous humor and histological evaluation were performed. Results: TAC-HPβCD eye drops demonstrated to reduce ocular inflammation, expression of IL-6, TNF-α, MIP-1α and leukocyte infiltration in aqueous humor. Conclusions: TAC-HPβCD eye drops showed beneficial effect in EIU model in rats, positioning as an alternative for uveitis treatment in case of corticosteroids resistance or intolerance.

A Case of Exfoliative Vesiculobullous Prurigo Pigmentosa Cured by Doxycycline and Topical Tacrolimus

Prurigo pigmentosa is a rare inflammatory skin disease characterized by an unexpected onset of diffuse erythematous papules and macules usually on the chest, neck, and back. These generally resolve, leaving reticular hyperpigmentation. Rarely, vesicular or bullous forms have been reported. We present a case of exfoliative vesiculobullous prurigo pigmentosa in a 13-year-old boy. He presented with symmetrical eruption of papules and vesicles on his back, neck, and chest in the last 10 days, causing pruritis and prickling sensation. Within a few days, the bullous lesions and all affected areas of the skin showed exfoliation. Histological study and clinical findings indicated the condition to be vesiculobullous prurigo pigmentosa with exfoliation. Treatment with doxycycline 200 mg/day and topical tacrolimus ointment showed a good response. The lesions resolved, leaving a light-brown reticulated hyperpigmentation. In conclusion, this was a case of exfoliative vesiculobullous prurigo pigmentosa in an adolescent man successfully treated with doxycycline and topical tacrolimus as an effective and safe treatment option.

Topical Tacrolimus in Patients with Hands Eczema Taking into Account the Severity of Dermatoses, Some Cytokine Profile Indicators, Content of Vitamin D and Genetic Polymorphism of the Glucocorticoid Receptor Gene

The purpose of the study was to evaluate and compare the therapeutic capacity of 0.1% topical tacrolimus ointment in patients with hand eczema who were resistant to glucocorticoid treatment, taking into account the severity of dermatosis, interleukin-17A and interleukin-2 concentrations, vitamin D and genetic polymorphism of the glucocorticoid receptor gene. Materials and methods. The venous blood of 143 patients with hand eczema aged (42.2±11.1) years was used in the study. During the patients examination the data on age, sex, body mass index (kg/m2), body mass index ≥25 kg/m2 (%), smoking, IgE (iu/ml), interleukin-17A (pg/ml), interleukin-2 (pg/ml), and 1,25(OH)2D3 (ng/ml) were obtained. The Hand Eczema Severity Index was also assessed in each subject. According to the Hand Eczema Severity Index value all patients were divided into three subgroups: mild, moderate and severe eczema. Patients with mild and moderate eczema were appointed topical glucocorticoid 0.1% mometasone furoate cream twice a day for 2 weeks. Patients with severe hand eczema was appointed additionally systemic corticosteroid – a solution of dexamethasone by intramuscular injection at the dose of 8 mg/day No. 3, then another 4 mg/day for other 2 days. After 2 weeks, individuals who did not respond well to glucocorticoid treatment were prescribed tacrolimus 0.1% ointment twice a day for 2 weeks. BclI SNP (rs41423247) of the glucocorticoid receptor gene (NR3C1) was determined using the polymerase chain reaction-restriction fragment length polymorphism method (Fleury et al. 2003). The statistical analysis was performed using the program SPSS 22.0. The quantitative variables were tested for normal distribution by the Shapiro-Wilk method. The comparisons of the means between the two subgroups were performed using Student's t-test for independent samples. The comparison of the frequencies distribution in the subgroups was performed using the Pearson test. The P value <0.05 was considered as significant. Results and discussion. Findings in a previous study showed that not all people with hand eczema responded well to treatment with topical 0.1% mometasone furoate cream and systemic glucocorticoid. After 2 weeks of topical tacrolimus, of 51 patients who were not responsive to glucocorticoid treatment, 39 responded well to therapy. The concentration of interleukin-17A in the blood serum of such people was significantly lower than in people who did not respond to treatment. Conclusion. We did not find any differences in the content of immunoglobulin E, interleukin-2, 1α,25(OH)2D3 and BclI polymorphism of the glucocorticoid receptor gene in the subjects under study

Efficacy of Topical Tacrolimus 0.05% Suspension in Steroid-Resistant and Steroid-Dependent Vernal Keratoconjunctivitis

Objective: The purpose of this study was to investigate the safety and effectiveness of topical tacrolimus 0.05% suspension in the management of prolonged steroid-dependent and -resistant vernal keratoconjunctivitis (VKC). Materials and methods: The present interventional prospective case series were conducted on the research units suffering from refractory VKC between 2017, April and 2020, December. Despite routine drug treatment, consisting of topical steroids (steroid-resistant group), all subjects exhibited active symptomatic illness or were dependent on topical steroids (steroid-dependent group). After discontinuation of all medications for at least 1 week, the patients received eye drop (topical tacrolimus 0.05%) minimally for six months. Objective and subjective signs and symptoms were examined for alterations after one week, and one and six months of treatment. Analyses were continued for probable systemic and ocular adverse effects. Results: The study included 28 eyes of 14 participants (including 4 females and 10 males), with the mean age of 22 ± 8 years (between 11 and 38 years), and the mean VKC duration of 12 ± 6 years (between 5 and 23 years), as well as follow up period of 10±2 months (between 6 and 12 months). The results showed an improvement (P<0.001) in the symptoms such as mucus discharge, foreign body sensation, photosensitivity, redness, burning and itching. The initial sign was conjunctival hyperemia, which improved one week after treatment. Other objective signs including, conjunctival and limbal papillary hypertrophy, corneal pannus and corneal punctate epithelial erosions improved at least one month after treatment. No changes were observed in corneal opacity during follow-up (p> 0.05). There were no systemic or ocular adverse effects. Conclusion: This is the first time that tacrolimus suspension drops 0.05%, are used in these cases. Topical tacrolimus 0.05% was shown to be an effectiveness and safe agent to treat the refractory VKC. This drug is recommended to be prescribed prior to the appearance of side effects such as corneal opacity, irreversible deficiency in limbal stem cell, and steroid side effects. Keywords: Vernal keratoconjunctivitis, Tacrolimus eye drop, Refractory