ABSTRACT
The cutaneous manifestations of Crohn's disease are myriad. A 15-year-old girl presented with recurrent lip swelling and eventual development of diarrhea and targetoid macules on the palms, feet, and back. She was finally diagnosed with Crohn's disease in the setting of a clinical presentation and histopathology consistent with orofacial granulomatosis and erythema multiforme. We review the literature and summarize reported occurrences of these cutaneous diseases in children with Crohn's disease.
Subject(s)
Crohn Disease/diagnosis , Erythema Multiforme/complications , Granulomatosis, Orofacial/diagnosis , Adolescent , Crohn Disease/complications , Crohn Disease/drug therapy , Female , Glucocorticoids/therapeutic use , Granulomatosis, Orofacial/complications , Humans , Immunosuppressive Agents/therapeutic use , Skin/pathologyABSTRACT
Benign melanocytic nevi are slowly growing acquiredor congenital tumors with varied morphology,commonly encountered in dermatology clinics. Anytumor with rapid clinical growth must be assessedcarefully in order to exclude malignancy. We report awoman with a histopathologically benign intradermalnevus that presented as a rapidly evolving largecutaneous mass on the ear. Owing to the discrepancybetween the clinical and histopathological findings,an extensive histopathological work-up involvingmany deeper sections, immunohistochemical stains,and fluorescent in situ hybridization (FISH) analysiswas conducted in order to rule out malignancy.
Subject(s)
Ear Neoplasms/diagnosis , Nevus, Intradermal/diagnosis , Nevus, Pigmented/diagnosis , Skin Neoplasms/diagnosis , Ear Neoplasms/pathology , Female , Humans , Middle Aged , Nevus, Intradermal/pathology , Nevus, Pigmented/pathology , Skin Neoplasms/pathologyABSTRACT
Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years.
ABSTRACT
With improved outcomes associated with radiotherapy (RT), post-irradiation tumors are increasingly seen in long-term cancer survivors. We report a case of a young woman who presented with a three-year history of a vascular lesion on the temple, previously irradiated for a childhood brain tumor. The history of radiation, the clinical appearance, and the biopsy findings of an atypical vascular proliferation in the dermis, were worrisome for a malignant vascular neoplasm and prompted surgical excision. However, further tissue analysis of the excised specimen confirmed a benign atypical vascular lesion (AVL) overlying a banal pilar cyst. Distinguishing post-radiation benign from malignant vascular lesions can be difficult because they share overlapping clinical and histopathologic features. Thus, any vascular lesion that occurs in a previously irradiated field should be excised completely with tumor-free margins and examined histologically.
Subject(s)
Astrocytoma/radiotherapy , Brain Neoplasms/radiotherapy , Neoplasms, Radiation-Induced/pathology , Neoplasms, Vascular Tissue/pathology , Skin Neoplasms/pathology , Epidermal Cyst/pathology , Epidermal Cyst/surgery , Female , Humans , Neoplasms, Vascular Tissue/etiology , Neoplasms, Vascular Tissue/surgery , Radiotherapy/adverse effects , Skin Neoplasms/etiology , Skin Neoplasms/surgery , Young AdultABSTRACT
Denileukin diftitox (Ontak) is an immunotoxin used in the treatment of cutaneous T-cell lymphomas. Vascular leak syndrome is a known complication of this therapy, although the syndrome is most often self-limited. We report the case of a patient with cutaneous gamma/delta (gammadelta) T-cell lymphoma and previous undiagnosed liver disease treated with denileukin diftitox. Just 4 days after initiating drug therapy, the patient developed profound vascular leak syndrome characterized by a rapid fall in his previously normal serum albumin to levels below the limit of detection. The patient then quickly deteriorated into rhabdomyolysis and eventual death. To our knowledge, this is the first report of a death directly related to denileukin diftitox therapy. The purpose of this case is to increase awareness and improve management of patients who are treated with denileukin diftitox with resulting vascular leak syndrome leading to hypoalbuminemia.
Subject(s)
Diphtheria Toxin/adverse effects , Diphtheria Toxin/therapeutic use , Fibrosis/complications , Interleukin-2/adverse effects , Interleukin-2/therapeutic use , Lymphoma, T-Cell, Cutaneous/complications , Lymphoma, T-Cell, Cutaneous/drug therapy , Vascular Diseases/chemically induced , Diphtheria Toxin/administration & dosage , Fatal Outcome , Fibrosis/drug therapy , Fibrosis/pathology , Humans , Interleukin-2/administration & dosage , Lymphoma, T-Cell, Cutaneous/pathology , Male , Middle Aged , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Syndrome , Treatment FailureABSTRACT
The dual-function Rel(Mtb) protein from Mycobacterium tuberculosis catalyzes both the synthesis and hydrolysis of (p)ppGpp, the effector of the stringent response. In our previous work [Avarbock, D., Avarbock, A., and Rubin, H. (2000) Biochemistry 39, 11640], we presented evidence that the Rel(Mtb) protein might catalyze its two opposing reactions at distinct active sites. In the study presented here, we purified and characterized fragments of the 738-amino acid Rel(Mtb) protein and confirmed the hypothesis that amino acid fragment 1-394 contains both synthesis and hydrolysis activities, amino acid fragment 87-394 contains only (p)ppGpp synthesis activity, and amino acid fragment 1-181 contains only (p)ppGpp hydrolysis activity. Mutation of specific residues within fragment 1-394 results in the loss of synthetic activity and retention of hydrolysis (G241E and H344Y) or loss of hydrolytic activity with retention of synthesis (H80A and D81A). The C-terminally cleaved Rel(Mtb) fragment proteins have basal activities similar to that of full-length Rel(Mtb), but are no longer regulated by the previously described Rel(Mtb) activating complex (RAC). Residues within the C-terminus of Rel(Mtb) (D632A and C633A) are shown to have a role in interaction with the RAC. Additionally, size exclusion chromatography indicates Rel(Mtb) forms trimers and removal of the C-terminus results in monomers. The C-terminal deletion, 1-394, which exists as a mixture of monomers and trimers, will dissociate from the trimer state upon the addition of substrate. Furthermore, the trimer state of fragment 1-394 appears to be a catalytically less efficient state than the monomer state.
Subject(s)
Ligases/chemistry , Multienzyme Complexes/chemistry , Mycobacterium tuberculosis/enzymology , Pyrophosphatases/chemistry , Binding Sites , Catalytic Domain , Enzyme Stability , Hydrolysis , Ligases/biosynthesis , Ligases/genetics , Ligases/metabolism , Magnesium/chemistry , Multienzyme Complexes/biosynthesis , Multienzyme Complexes/genetics , Multienzyme Complexes/metabolism , Mycobacterium tuberculosis/genetics , Peptide Fragments/chemistry , Peptide Fragments/genetics , Pyrophosphatases/biosynthesis , Pyrophosphatases/genetics , Pyrophosphatases/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/metabolismABSTRACT
Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. Analysis of the Mtb genome predicts the existence of a branched aerobic respiratory chain terminating in a cytochrome bd system and a cytochrome aa(3) system. Both chains can be initiated with type II NADH:menaquinone oxidoreductase. We present a detailed biochemical characterization of the aerobic respiratory chains from Mtb and show that phenothiazine analogs specifically inhibit NADH:menaquinone oxidoreductase activity. The emergence of drug-resistant strains of Mtb has prompted a search for antimycobacterial agents. Several phenothiazines analogs are highly tuberculocidal in vitro, suppress Mtb growth in a mouse model of acute infection, and represent lead compounds that may give rise to a class of selective antibiotics.