Tobramycin and antiglaucoma agents as increasing culprits of periorbital allergic contact dermatitis from topical ophthalmic medications: A 24-year study from Turkey.

BACKGROUND: Allergic contact dermatitis (ACD) from topical ophthalmic medications (TOMs) poses an additional disease burden to patients who already suffer from eye problems. OBJECTIVES: To investigate the epidemiological/clinical profile of patients with periorbital ACD from TOMs in Turkey. PATIENTS AND METHODS: This was a retrospective, cross-sectional, single tertiary centre study based on files of 75 patch tested patients with suspected periorbital ACD from TOMs among a total of 2801 consecutively patch tested patients with suspected ACD of any origin between 1996 and 2019. RESULTS: Periorbital ACD was diagnosed in 25 of 75 (33.3%) patients (female:male = 1.8:1; age range: 6-85 years) with suspected ACD from TOMs showing an overall prevalence of 0.9% (25/2801) among the whole patch test population. Atopy was not present. Tobramycin-containing TOMs were the most frequent culprits, followed by antiglaucoma preparations. Their frequency increased, whereas no new cases of neomycin-induced ACD were observed after 2011. Positivities with thimerosal were of unknown clinical relevance, while benzalkonium chloride (BAC) caused ACD in two patients. The diagnosis would be missed in each 20% of patients without performing day (D) 4 and D7 readings and strip-patch testing. Ten culprits were identified only by testing with patients' own TOMs in eight (32%) patients. CONCLUSIONS: Aminoglycosides, particularly tobramycin, were the leading cause of ACD from TOMs. The frequency of ACD from tobramycin and antiglaucoma medications increased after 2011. BAC was a rare but important allergen. Additional D4 and D7 readings, strip-patch testing, and testing with patients' own TOMs seem essential when patch testing with eye medications.

Long-term dupilumab therapy in Netherton syndrome with severe atopic manifestations: Case report and review of the literature.

We herein present a unique patient of Netherton syndrome (NS) with ichthyosis linearis circumflexa (ILC) lesions associated with severe atopic manifestations since infancy, showing different responses of atopic and ILC lesions to a 2-year dupilumab therapy. The atopic eczematous lesions and pruritus healed remarkably, dramatically improving the patient's quality of life, whilst the scalp hair showed a clinical and light microscopic improvement. The additional recovery in axillary/pubic/extremity hair growth, sweating and nail growth in the presented case was not previously reported in NS patients treated with dupilumab. However, dupilumab had no therapeutic effect on ILC lesions which were not pruritic and showed a treatment-independent wax and waned course.

Sorbitan sesquioleate: a rare contact allergen that is also an important indicator of allergic contact dermatitis from crossreacting compounds as well as for false-positive fragrance allergy.

BACKGROUND: Controversy exists about the addition of sorbitan sesquioleate (SSO) to the European baseline series for concomitant patch testing, particularly with fragrance mix (FM) I and Myroxylone pereirae (MP), which both contain SSO as an emulsifier. AIM: To investigate SSO contact sensitization and concomitant positive patch test reactions to FM I or MP in Turkey. METHODS: This was a retrospective analysis of 840 patients consecutively patch tested with SSO 20% petrolatum between 1996 and 2020. RESULTS: The prevalence of SSO sensitization was 0.6% (5 of 840). In four of the five patients, clinical relevance could be established from SSO crossreactants, mainly in moisturizers and topical pharmaceuticals other than corticosteroids. Positive patch test reactions with unknown clinical relevance were observed to FM I or MP (both containing 5% SSO) in 71.4% of patients with a positive/questionable positive reaction to SSO (P < 0.001) and to other patch test allergens containing 1-5% SSO. CONCLUSIONS: SSO was a very good indicator for positive patch test reaction with unknown clinical relevance to fragrances and other allergens containing 1-5% SSO. We suggest that SSO should be tested as a negative control with any commercially available patch test allergen containing SSO at any concentration. Moreover, clinicians should be alert for SSO synonyms and for other sorbitan derivatives in product labels, as SSO itself might not be the culprit but an indicator for crossreacting allergens.

Long-term efficacy and safety of ustekinumab for moderate-to-severe psoriasis: A 9-year real-life experience from a tertiary referral center in Turkey.

There is a paucity of data on long-term (≥5-year) outcomes of ustekinumab therapy for psoriasis in real-life clinical practice. This observational, retrospective study aimed to evaluate the long-term efficacy and safety profile of ustekinumab in 52 adult patients with moderate-to-severe chronic plaque psoriasis who were treated with ustekinumab for at least 28 weeks and a maximum of 105 months in our tertiary referral center in Turkey, between 2010 and 2019. Response to therapy was assessed using Psoriasis Area and Severity Index (PASI). Logistic regression analysis was performed to determine significant associations (p-value <0.05) with response to treatment. The PASI50, PASI75, PASI90, and PASI100 response rates were 97.8%, 88.9%, 53.3%, and 35.5%, respectively, at year 1 and 100%, 80.0%, 60.0%, and 40.0%, respectively, at year 5. Non-obesity was independently associated with PASI90 response at year 2 (p = 0.043), while biologic-naivety was independently associated with PASI90 responses at year 2 (p = 0.047) and year 3 (p = 0.021). An absolute PASI score of ≤3 was achieved by 82.2% and 80.0% of the patients at year 1 and year 5, respectively. Nine patients received adjuvant therapy and nine underwent ustekinumab dose escalation. These strategies were effective for recapturing clinical response in most patients. Ustekinumab was generally well-tolerated with no dose-related and cumulative toxicity, or drug interaction over a mean of 33.5 ± 21.1 months. The main reasons for discontinuation were secondary failure and loss to follow-up. Our 9-year real-life clinical experience demonstrates that ustekinumab is an efficacious and safe treatment option for long-term therapy of moderate-to-severe plaque psoriasis.

Inflammatory status might direct ILC and NK cells to IL-17 expressing ILC3 and NK subsets in Behcet's disease.

Innate lymphoid cells (ILCs) are lymphoid cells that have important effector and regulatory functions in innate immunity and tissue remodeling. Uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. Behcet's disease (BD) is a complex systemic inflammatory disorder of unknown etiology. It has been shown that natural killer (NK) cells may play an immunoregulatory role in BD, however the role of ILCs is unknown. In this study, the levels and functions of ILCs and NK cell subsets in BD patients were investigated. Cell surface and cytotoxic granules (perforin and granzyme) expression of NK cells and ILCs were evaluated and labeled according to whole blood lysing protocol in peripheral blood samples obtained from the patients and healthy subjects. Cytokine levels of NK cells were investigated in stimulated peripheral blood mononuclear cells. All data were analyzed by flow cytometry. Total ILC and ILC3+ cells were increased in active BD patients compared to inactive BD patients and healthy subjects. There was no significant difference between the patients and healthy subjects regarding NK cell surface and intracellular molecule expression. Although, an increase in IFN-γ and IL-17, and a decrease in IL-4 levels were observed in CD56dim NK cell subset of BD patients. Recent studies showed increased neutrophilic infiltration and IL-17 secreting Th17 cells in BD patients. It is known that ILC3+cells are similar to Th17 subset regarding their cytokine profile and transcription factor expression patterns. Results of current study may suggest that inflammatory microenvironment in BD patients might direct ILC cells to differentiate into ILC3+ subset, and IL-17 released by NK cells might have a role in neutrophilic infiltration.

Comparison of three different dose regimens of methylprednisolone as initial therapy for pemphigus vulgaris of moderate severity: A single-center retrospective study from Turkey.

BACKGROUND: Currently, no consensus exists on the dosing regimen of corticosteroids in relation to disease severity in pemphigus vulgaris. OBJECTIVE: To evaluate the efficacy of three initial dose regimens of methylprednisolone in the treatment of moderate pemphigus. METHODS: We retrospectively analysed the data of 46 patients with moderate pemphigus vulgaris, who initially received either low (0.60-0.80 mg/kg/day), moderate (0.81-1.20 mg/kg/day) or high (1.21-2.0 mg/kg/day) doses of methylprednisolone. RESULTS: The median time to disease control and hospital stay was shortest in the high-dose group (8.5 days and 27.5 days, respectively). The low-dose group had the highest rate of adjuvant therapy (88.8%, P = 0.035). Cumulative methylprednisolone doses and corticosteroid-related adverse events were similar in the moderate- and high-dose groups. The initial methylprednisolone dose showed a significant inverse correlation with time to disease control (r = -0.319, P = 0.031) and a weak inverse correlation with length of hospital stay (r = -0.282, P = 0.058). LIMITATIONS: Retrospective design and small patient size are major limitations. CONCLUSION: In the treatment of moderate pemphigus vulgaris, high initial doses of corticosteroid seem to provide early disease control and shortened hospital stay without notable increases in cumulative corticosteroid doses. This treatment strategy may lower the risk for nosocomial infections and reduce the economic burden of pemphigus.

Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi-drug refractory patients: A case series of high efficacy and safety profile.

Secukinumab, the first monoclonal antibody that inhibits interleukin-17A, has been shown to have rapid and long-lasting efficacy in the treatment of moderate-to-severe psoriasis. However, there are still difficult-to-treat cases in which even dose-escalation fails to provide a clinical response. In such cases, combining secukinumab with a conventional systemic agent may be a rational approach. Although methotrexate is most commonly preferred, acitretin may also be considered a good alternative, with its lower hepatotoxic potential. Data are limited regarding the use of combination therapy of secukinumab and acitretin for psoriasis. We herein present three patients with chronic plaque, generalized pustular and erythrodermic psoriasis, respectively, accompanied by multiple comorbidities, in whom skin clearance could not be achieved with several conventional and biologic therapies (including escalated dose regimens of secukinumab in two patients). Alternatively, we used a combination of secukinumab with low-dose acitretin, which resulted in a complete or almost complete skin clearance in all patients, with no adverse events or increased toxicity. Based on our real-life clinical experience with those patients, acitretin seems an effective and safe option to be used in combination with secukinumab. Even in patients who are refractory to multiple drugs including escalated doses of secukinumab, the addition of low-dose acitretin may be helpful in achieving treatment goals, decreasing the need for switching to another biologic therapy.

Methylchloroisothiazolinone/methylisothiazolinone and methylisothiazolinone contact allergy: A 24-year, single-center, retrospective cohort study from Turkey.

BACKGROUND: Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI allergy caused a global epidemic during the period 2010 to 2015, reaching its peak in 2013/14. OBJECTIVE: To investigate the characteristics of MCI/MI and MI allergy in Turkey over 24 years. METHODS: A total of 2310 patients patch tested between 1996 and 2019 with MCI/MI 0.01% aq. or MCI/MI 0.02% aq., with or without MI 0.2% aq., were analyzed. RESULTS: The overall prevalence of contact sensitization was 3.3% (n = 77) with a peak level of 16.4% in 2015. The prevalence gradually decreased thereafter, but was still high (6.5%) in 2019. Seventy-three patients had clinically relevant sensitizations. MI could detect clinically relevant sensitizations in all seven patients with a negative patch test reaction to MCI/MI 0.02%. Non-occupational allergic contact dermatitis (ACD) was most frequently seen, mainly in women, with hand/face eczema from rinse-off or leave-on cosmetics, such as wet wipes. Occupational ACD was mainly seen among men with airborne eczema from wall paints in house painters, or with hand eczema from hair gel/wax in men's barbers. CONCLUSIONS: The prevalence of MCI/MI and MI sensitization in Turkey following the peak in 2015 is still high. This is probably due to the currently allowed level of 100 ppm for MI in rinse-off cosmetics. This needs to be urgently reduced.

Use of biologic therapies for psoriasis during pregnancy and long-term outcomes of exposed children: A 14-year real-life experience at a tertiary center in Turkey and review of the literature.

Data regarding the use of biologic therapies for psoriasis during pregnancy are scarce with even more limited knowledge about the long-term safety of in utero exposure. We retrospectively evaluated nine pregnancies in six women with psoriasis who were exposed to biologic therapies between 2006 and 2019 in our psoriasis clinic, a tertiary referral center in Turkey. Pregnancy outcomes included the delivery of seven healthy babies without any complications, one elective abortion, and one ectopic pregnancy. All exposed children, aged between 14 months and 13 years (median age: 4.0 years), showed normal growth and neuropsychological development without immunodeficiencies, allergies, malignancies or other diseases. Based on up-to-date collective data in the literature and our real-life clinical experience presented here, exposure to biologic therapies during pregnancy for psoriasis does not seem to be associated with adverse pregnancy or neonatal outcomes. Our results are also reassuring with respect to long-term outcomes of exposed children, but need to be confirmed through further large prospective studies. Nevertheless, use of biologic therapies during late pregnancy, particularly during the third trimester, should be reserved for high-need patients with psoriasis and definitely requires a delicate risk/benefit balance on a case-by-case basis.

Infliximab for the treatment of recalcitrant generalized pustular psoriasis of pregnancy: Report of a challenging case.

Pustular psoriasis of pregnancy (PPP), also known as impetigo herpetiformis, is a rare gestational dermatosis that may induce life-threatening complications for both the mother and fetus. Treatment of recalcitrant generalized PPP may be challenging as available therapeutic options are limited. We herein present a 24-year-old pregnant woman with generalized PPP accompanied by high fever, fatigue, leukocytosis, and elevated levels of serum acute phase reactants. The patient was resistant to a combination treatment of high-dose cyclosporine (7.5 mg/kg/d, peroral), systemic methylprednisolone (1 mg/kg/d, intramuscular), and empirical antibiotherapy. However, she dramatically improved with infliximab (5 mg/kg, intravenous infusion), which was introduced at week 28 of pregnancy. Even within 24 hours after the first infusion of infliximab, pustular lesions began to regress with a rapid decline in fever. Following the third infusion, clearance of pustular lesions with a slight erythema was observed. Serum levels of leukocytes and acute phase reactants returned to normal. There were no adverse events related to infliximab therapy. At 40 weeks, the patient gave birth to a healthy baby. Our experience reported herein suggests that infliximab may serve as a rapidly acting, highly effective, and well-tolerated "rescue" therapy in recalcitrant generalized PPP, which poses a big therapeutic challenge for clinicians.

Doxepin in difficult-to-treat chronic urticaria: A retrospective, cross-sectional study from Turkey.

Doxepin is an old tricyclic antidepressant, whose efficacy in chronic urticaria had been well documented until 1990. However, over the past three decades, there has been limited data on its use. We aimed to assess the efficacy and safety of doxepin in the treatment of patients with chronic urticaria who were poorly responsive to antihistamines. In this retrospective, cross-sectional, single-center study from Turkey, data were examined from patients with chronic urticaria who had poor antihistamine responses and received doxepin therapy from 1998 to 2017. Patient data were analyzed with regard to the duration of the disease, age, sex, treatment outcomes using a weekly urticaria activity score (UAS7), and adverse effects of doxepin therapy. A reduction of ≥90% in UAS7 was defined as "complete response," 30-89% as "partial response" and <30% as "no significant response." Thirty-six patients were included in this study. Doxepin was effective in a majority (n = 27, 75%) of the patients with a short onset time. Sixteen patients (44.4%) showed a complete response. Mild sedative and anticholinergic side effects were well tolerated. Doxepin seems to be a reasonable, efficient, and affordable alternative for the treatment of chronic urticaria in patients who respond poorly to antihistamine therapy.

Psoriasiform skin eruption in a patient receiving certolizumab-pegol for ankylosing spondylitis: Report of a case and review of the literature.

Certolizumab-pegol is the first and only pegylated TNF-α antagonist approved in the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. We herein present a case of certolizumab-pegol induced generalized psoriasiform eruption in a patient with ankylosing spondylitis. The diagnosis was based on typical clinical and histopathological findings and further confirmed with Naranjo Adverse Drug Reaction Probability Scale which revealed a total score of nine supporting a definite causal relationship between the drug and skin eruption. As an important finding, a significant improvement of the generalized plaque lesions was achieved upon a therapy including high-potency topical corticosteroid and oral antihistamine without discontinuation of certolizumab-pegol. Moreover, we also present a literature review of the previously published cases with certolizumab-pegol induced psoriasiform eruption. Since all of these cases had Crohn's disease or rheumatoid arthritis as the underlying disease, this is the first case report of certolizumab-pegol induced psoriasiform eruption in a patient with ankylosing spondylitis, to the best of our knowledge.

A recalcitrant case of Jacquet erosive diaper dermatitis after surgery for Hirschsprung disease in a boy with Waardenburg-Shah syndrome.

We herein present a 4 year-old boy with Waardenburg-Shah syndrome who developed Jacquet erosive diaper dermatitis following a total colectomy and ileoanal anastomosis procedure for Hirschsprung disease. The diagnosis was made according to history and typical clinical findings. Complete resolution of the recalcitrant lesions after an ileostomy procedure supported the diagnosis. This case highlights the importance of being familiar with the predisposing factors and clinical presentation of this rare and severe form of chronic irritant dermatitis, since it may easily be misdiagnosed as other diseases in children and may lead to unnecessary diagnostic procedures, treatments, and anxiety due to suspicion of child abuse.