tacrolimus and Stevens-Johnson-Syndrome

Common pediatric skin conditions such as infantile atopic dermatitis, vitiligo, hemangiomas of infancy, warts, and molluscum contagiosum do not always respond to standard therapy. In some settings pediatricians will use "off-label" medications if the benefit-to-risk ratio is favorable. This article reviews important literature from the past year related to "off-label" immune-based treatment of skin disease, using the topical immunomodulators tacrolimus, pimecrolimus, and imiquimod, as well as intravenous Ig.. The topical immunomodulators tacrolimus and pimecrolimus have been embraced by pediatricians as long awaited alternatives for treating atopic dermatitis in children 2 years of age and older. Their unique appeal as nonsteroidal topical agents with good safety profiles has led to their frequent use for unapproved indications. A number of recent publications detail their use in infantile atopic dermatitis in children as young as 3 months of age, as well as use in other conditions such as vitiligo. Imiquimod, another topical immunomodulator, approved for genital wart treatment in adults, has also been examined for "off-label" pediatric use in nongenital warts, molluscum contagiosum, hemangiomas of infancy, and basal cell carcinoma. Finally, "off-label" use of intravenous Ig has been evaluated for the life-threatening dermatoses Stevens-Johnson syndrome and toxic epidermal necrolysis.. In the absence of larger controlled trials, pediatricians must consider the cumulative weight of smaller studies with their personal experience when assessing any role for "off label" therapy. The recent literature reviewed herein will facilitate such assessments of the non-steroid topical immune modifiers tacrolimus, pimecrolimus, and imiquimod as well as intravenous immunoglobulin.

Topics: Adjuvants, Immunologic; Aminoquinolines; Child; Clinical Trials as Topic; Dermatitis, Atopic; Hemangioma; Humans; Imiquimod; Immunoglobulins; Immunologic Factors; Immunosuppressive Agents; Infant; Molluscum Contagiosum; Skin; Skin Diseases; Stevens-Johnson Syndrome; Tacrolimus; Vitiligo; Warts

Acute graft-versus-host disease (aGVHD) is a severe and fatal complication after orthotopic liver transplantation (OLT). Clinical manifestations of severe aGVHD can resemble drug-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and there are also various medications, such as antibiotics and immunosuppressants, used after transplantation, causing a diagnostic dilemma. Furthermore, there have been no standardized diagnostic and therapeutic strategies for OLT-aGVHD due to its rarity.. A 52-year-old man presented with generalized maculopapular eruptions, fever, and pancytopenia 1 month after OLT and 4 days after taking sulfamethoxazole/trimethoprim. After assessment of the scoring criteria for drug causality of drug allergy, histopathological findings of skin biopsy, lymphocyte activation test of the potential offending drug, and microchimerism study, the diagnosis was in favor of aGVHD mimicking SJS/TEN. Considering severe sepsis, the anti-tumor necrosis factor alpha (TNF-α) agent, etanercept, was used to replace tacrolimus and corticosteroid. Skin lesions resolved gradually after anti-TNF-α biologics rescue; tacrolimus and corticosteroid therapy were re-administrated after controlling sepsis. Pancytopenia recovered and the patient was discharged in a stable condition.. We demonstrated a diagnostic strategy for OLT-aGVHD. Targeting therapy with anti-TNF-α blockade and a temporary withdrawal of traditional immunosuppressants may be among effective and safe therapeutic options of OLT-aGVHD for those with severe sepsis.

Topics: Adrenal Cortex Hormones; Graft vs Host Disease; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Pancytopenia; Sepsis; Stevens-Johnson Syndrome; Tacrolimus; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha

Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening disease. Vanishing bile duct syndrome (VBDS) is a rare cause of progressive cholestasis. Both syndromes are mostly related with drugs. We report a case of a patient with ciprofloxacin-induced SJS and acute onset of VBDS, and reviewed the related literature. It is the first case of ciprofloxacin-induced VBDS successfully treated with tacrolimus. This case reminds physicians of the importance of drug reactions, their severity, techniques for diagnosis and methods of management.

Topics: Adult; Bile Duct Diseases; Ciprofloxacin; Deglutition Disorders; Dysuria; Female; Humans; Immunosuppressive Agents; Stevens-Johnson Syndrome; Tacrolimus; Treatment Outcome

Topics: Bile Duct Diseases; Bile Ducts, Intrahepatic; Carbamazepine; Child, Preschool; Cholestasis; Hepatitis B; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Methylprednisolone; Pancreatitis; Stevens-Johnson Syndrome; Tacrolimus

Topics: Adjuvants, Immunologic; Aminoquinolines; Condylomata Acuminata; Dermatitis; Dermatology; Humans; Imiquimod; Interferon Inducers; Keratolytic Agents; Stevens-Johnson Syndrome; Tacrolimus

Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.

Topics: Acute Disease; Adult; Bile Duct Diseases; Biopsy; Child; Cholestasis; Female; Humans; Ibuprofen; Liver; Liver Cirrhosis; Prednisone; Stevens-Johnson Syndrome; Tacrolimus; Time Factors; Ursodeoxycholic Acid