Efficacy and safety of tacrolimus ointment in pediatric Patients with moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an immunological skin disease. It is common in pediatric populations and often requires topical steroid treatment. Moderate to severe AD may not respond to topical steroids. They often require systemic steroids, which may result in growth retardation. Protopic, a non-steroid, tacrolimus based ointment which is a calcinurin inhibitor has been proved to be effective in caucacian with AD. OBJECTIVE: To evaluate safety and efficacy of 0.03% tacrolimus ointment (Protopic&) in moderate to severe AD in pediatric patients age 2-12 years. MATERIAL AND METHOD: This was a one month multicenter open-label clinical trial using tacrolimus ointment twice daily in 61 subjects with moderate to severe AD from September to December 2004. Efficacy assessments were measured by Physician's Global Evaluation of Clinical Response (PhGECR), Eczema area and Severity Index (EASI), Patient's Global Evaluation of Clinical Response (PaGECR), and Quality of Life (QOL). Safety assessment was measured by incidence rate of adverse events. RESULTS: Fifty-eight patients completed the studies. Twenty-two patients were male; thirty-nine patients were female. Twenty-nine patients had moderate AD. Thirty-two patients had severe AD. Three cases had discontinued treatment at the third week due to increase in severity. Over all PhGECR were significantly increased, 94% showed moderate improvement in PhGECR at week 4 or end of treatment (EOT)and 83% had better improvement in PaGECR at EOT Within 7 days, tacrolimus demonstrated rapid onset in reduction of EASI score and itch in patients. Mean QOL were significantly decreased at the end of the present study. Incidence of adverse events included application site burning (21%), itching (17%), pruritus (9%), infections(3%), and erythema and folliculitis (2%). Burning sensation, erythema, pruritus and itching were resolved after the first week. CONCLUSION: Topical tacrolimus ointment is effective and safe in moderate to severe AD. It significantly improved PhGECR, EASI, PaGECR, and QOL in pediatric patients after the first week of treatment and continued through the end of the study. The major adverse events were burning, itching, and pruritus, which were resolved within the first week of therapy.

Henoch-Schonlein purpura: clinical manifestations and long-term outcomes in Thai children.

The clinical features of 47 children with Henoch-Schonlein purpura (HSP) are presented. The most common ages at presentation ranged from 3-5 years. Duration of data collection was 60 months. The peak incidence was from December to February. The organ involvements included skin (100%), gastrointestinal tract (74.5%), renal (46.8%) and joint (42.6%). Renal involvement was detected within the first 2 months in 16 cases (72.7%) but was delayed until 6 months after diagnosis in 6 cases. No risk factors for renal involvement could be identified. The mean duration of follow-up was 2.6 years (range 1-5 years). Six out of 16 (37.5%) patients had residual renal diseases but none were end stage. Recurrent episodes of abdominal pain and skin purpura were found in a few cases during the first year. Overall prognosis of HSP is good and long-term morbidity is predominantly associated with renal involvement. Patients with initially normal urinalysis should have sequential urinary examination at least for 6 months.

Neonatal lupus erythematosus: clinical manifestations and management.

The authors report 6 cases of neonatal lupus erythematosus (NLE) who were seen at Ramathibodi Hospital from 1993 to 2000. The female to male ratio was 1:5. Cutaneous lesions were the major manifestation in all cases. Other clinical manifestations were thrombocytopenia, hepatosplenomegaly and mild elevation of liver enzymes. Skin rashes mostly erupted at 3-6 weeks old. None had a complete heart block but one had abnormal electrocardiograph (ECG) changes compatible with Wolff-Parkinson-White syndrome (WPW). Four of six patients had thrombocytopenia. All of the abnormalities resolved spontaneously except thrombocytopenia. Three of six needed blood transfusion to replace blood loss from gastrointestinal bleeding. Intravenous immunoglobulin (IVIG) 2 g/kg was given in 3 cases with good response in two of three cases. Platelets rose rapidly and maintained at a normal level within 24-48 hours. Combined therapy with corticosteroid 2 mg/kg was given to 1 case with good outcome. Telangiectasia was the most common sequelae especially in patients who had periorbital lesions resembling raccoon's eyes. The authors conclude that IVIG in the dose of 1 g/kg for 1-2 days is an effective treatment for NLE with severe thrombocytopenia especially when corticosteroid is contraindicated.

Antineutrophilic cytoplasmic antibody-positive systemic vasculitis associated with propylthiouracil therapy: report of 2 children with Graves' disease.

Systemic vasculitis is a rare complication of therapy with antithyroid medication. Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis has been described in patients treated with propylthiouracil (PTU) and methimazole (MMI). The majority of cases have underlying Graves' disease. The authors report 2 children who developed ANCA-associated systemic vasculitis during PTU therapy of Graves' disease. One patient, after PTU treatment for 3 years, developed severe systemic vasculitis. After 3 weeks of arthritis, she abruptly presented with hematuria, proteinuria and edema concomitant with anemia. Her serum creatinine was elevated, to 6 mg/dl. Renal biopsy revealed crescentic glomerulonephritis. After admission, she developed intracerebral hemorrhage and pulmonary hemorrhage. She had positive perinuclear-ANCA (p-ANCA) with a titer of 1:160. Despite intensive therapy with immunosuppressive agents and plasmapheresis, as well as discontinuation of PTU, she died of the complications of severe systemic vasculitis. The other patient developed fever, arthralgia and leukocytoclastic vasculitis of the skin during treatment with PTU for about 2 years. Her symptoms and skin lesions disappeared after discontinuation of PTU. However, she has had a persistently high titer of p-ANCA 1:320 through 17 months follow-up time. Thus, patients who are treated with PTU can develop ANCA-positive vasculitis in a mild or severe form. Therefore, they should be carefully followed and monitored, not only for their thyroid status but also the serious complications of PTU.

Sebaceous nevus syndrome as the underlying cause of intractable seizures in a one-month-old infant.

A one-month-old male infant with generalized seizures since 2 days old was evaluated at the Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. His seizures were initially characterized as focal movement of the right upper and lower limbs followed by generalized tonic. Initially, phenobarbital was administered but failed to control his seizures. Physical examination revealed generalized mild hypotonia with a hyperpigmented brownish patch affecting the left side of his face. The initial diagnosis was sebaceous nevus syndrome which is one of the neurocutaneous syndromes. The diagnosis was confirmed by skin biopsy of the affected lesion. The literature was reviewed and discussed. The authors emphasized the importance of thorough physical examination including evaluation of specific skin lesion which would be a leading clue in making the diagnosis of symptomatic epilepsy in infants.

Congenital self-healing Langerhans cell histiocytosis with pulmonary involvement: spontaneous regression.

Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare condition which may present at birth or during the neonatal period. It is usually characterized by eruption of multiple, discrete and red-brown papules and nodules which may increase in size and number during the first few weeks of life with spontaneous regression. Systemic signs are usually absent except for occasional mild hepatomegaly. The authors report a case of CSHLCH associated with multiple lung cysts with spontaneous regression. A healthy full term male infant presented at birth with numerous diffuse discrete dark-red papules sized 0.2-1.0 cm scattered on the eyelids, temporal areas of the scalp, neck, palms and soles. Histologic findings were mixed inflammatory infiltration of numerous histiocytes. Immunochemistry findings were S-100 and CDla positive consistent with CSHLCH. Hepatomegaly and multiple lung cysts were detected at 1 month old. Since he was healthy, no medication was given except for close monitoring. At 2 months of age, hepatomegaly was resolved but the liver had sclerosing change. Skin lesions regressed completely at the age of 4 months. Lung cysts were markedly improved at 7 months old and completely resolved at 1 year old. Spontaneous regression in CSHLCH with lung involvement has never been reported in Thailand.

Therapeutic efficacy and safety of loratadine syrup in childhood atopic dermatitis treated with mometasone furoate 0.1 per cent cream.

Atopic dermatitis is a common skin disease in Thai children. The treatment of atopic dermatitis requires topical corticosteroids, emollients, systemic antihistamine as well as avoidance of the precipitating factors. A double blind multicenter placebo controlled study was conducted to assess the therapeutic efficacy of topical mometasone furoate 0.1 per cent cream in combination with loratadine syrup. Forty-eight patients, 23 boys and 25 girls, mean age 73.67 months, with atopic dermatitis were included in the study. The severity of the disease was measured by using the SCORAD index including the degree of erythema, dryness, edema/papulation, oozing/crusting, lichenification, and excoriation. Total area involved was measured and a target area of dermatitis was selected for specific evaluation. The degree of clinical signs and pruritic symptom was graded. The sensation of pruritus, disturbance of sleep due to pruritus, and feeling of sleepiness in the morning were recorded. Mometasone furoate 0.1 per cent cream was applied to all patients once daily. One group received loratadine syrup and another group received placebo syrup. They were followed-up on day 5, 8 and 15. The severity of atopic dermatitis and pruritus significantly decreased after 14 days of treatment in both groups (p < 0.001). There was no difference in therapeutic response between the loratadine and placebo groups (p = 0.99). All signs examined had decreased by the end of the study. The result demonstrated that 0.1 per cent mometasone therapy is very effective for treating childhood atopic dermatitis. Loratadine did not show beneficial effect when combined with good topical corticosteroid but it was safe and had no serious side effect on the children.

Drug eruptions: the value of oral rechallenge test and patch test.

All in-and out-patients, who came for drug eruption consultation at the Dermatology Clinic, Ramathibodi Hospital from December 1997 to November 1998 were included in this study. Medical histories and physical examinations were performed by one of the authors. In suspected cases, a skin biopsy was performed to confirm the diagnosis. Patch test and oral challenge test were performed in some patients who had maculopapular, fixed drug eruption and acute generalized exanthematous pustulosis, with informed consent. Among 80 patients, the most common cutaneous reaction was maculopapular rash. Antimicrobial, drugs were the most common causative agents. The patch test was positive in only one patient from 12 cases. The oral provocative test was positive in two patients from 4 cases. It is concluded that oral provocative test is still necessary to get a definite diagnosis of causative agent. The value of patch test needs further study.