A pharmacogenetic basis for the safe and effective use of azathioprine and other thiopurine drugs in dermatologic patients.
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Alleles↗
Biomedical subjects
L E Gibson
Publications and source records attributed to L E Gibson.
Sweet syndrome: acute febrile neutrophilic dermatosis.
Sweet, in 1964, described a skin condition characterized by fever, leukocytosis, tender erythematous plaques, and, histopathologically, a predominantly neutrophilic dermal inflammation. However, other dermatologic conditions can present with similar clinical and histological features. Therefore, diagnostic criteria are important for the correct diagnosis. Use of systemic steroids is the treatment of choice for Sweet syndrome. A number of other medications can be useful at times, such as potassium iodide, dapsone, indomethacin, and colchicine.
Diagnosis, Differential↗
Lipomembranous changes in nodular-cystic fat necrosis.
Three cases of nodular-cystic fat necrosis presenting with focal lipomembranous changes are reported. The lesions consisted of solitary (cases 1 and 3) or multiple (case 2) subcutaneous nodules on the upper (case 1) or lower (cases 2 and 3) extremities which had evolved over weeks to years. At surgical excision, solitary or multiple, freely mobile nodules within a cystic cavity were observed. Histologically, encapsulated fat nodules showing variable amounts of necrosis without marked inflammatory changes were present. Focal lipomembranous changes were observed in some nodules. Our observations seem to support the concept that lipomembranous changes are nonspecific and uncommon patterns of fat necrosis caused by a wide variety of local or systemic events that may cause a compromise in the blood supply of the subcutaneous tissue.
Adipose Tissue↗
Henoch-Schönlein purpura: clinicopathologic correlation of cutaneous vascular IgA deposits and the relationship to leukocytoclastic vasculitis.
Significant cutaneous vascular IgA deposits are common in Henoch-Schönlein purpura but not in other vasculitides. The specificity for IgA vascular deposits for Henoch-Schönlein purpura is not well defined. To examine the specificity of IgA vascular deposits for this disease, we compared clinicopathologic features of 92 cases with IgA vascular deposits and a direct immunofluorescence impression of vasculitis with 90 similar cases without IgA deposits. Henoch-Schönlein purpura was diagnosed in 24% of cases with vascular IgA deposits on direct immunofluorescence examination. IgA deposits were frequent in erythema nodosum and venous stasis-related problems and in cryoglobulinemia, coagulopathic vasculopathies, and livedoid vasculitis. Of our cases, 78% exhibited vascular fluorescence with multiple conjugates. No histologic or immunofluorescence pattern alone was specific. The diagnostic specificity for Henoch-Schönlein purpura is improved if gastrointestinal involvement, upper respiratory infection, or age < 20 years is present. We propose diagnostic criteria for Henoch-Schönlein purpura incorporating clinical findings yielding sensitivity and specificity > 90%.
Biopsy↗
Sweet's syndrome: systemic signs and symptoms and associated disorders.
OBJECTIVE: To characterize the findings associated with acute febrile neutrophilic dermatosis (Sweet's syndrome [SS]) and the response of SS to treatment. DESIGN: We retrospectively reviewed 48 cases of SS encountered at the Mayo Clinic between 1980 and 1992. MATERIAL AND METHODS: Histopathologic specimens and medical records were studied to determine initial manifestations, patterns of involvement, systemic signs and symptoms (including mucosal, musculoskeletal, hematologic, pulmonary, hepatic, and renal findings), and conditions associated with SS. RESULTS: In patients with SS, the typical manifestations are the acute onset of tender, erythematous or violaceous nodules or plaques in association with fever, leukocytosis, and dermal neutrophilia. In our study group, the cutaneous lesions most frequently involved the arms and legs. Of our 48 patients, 26 (54%) had a hematopoietic, plasma cell, or malignant disorder, and many of these patients had associated anemia, especially the male patients. No single laboratory finding specifically indicated an association with serious systemic disease. Most patients were treated with a tapering dose of prednisone, which yielded a good response. CONCLUSION: Clinical acumen and appropriate laboratory tests are the main requirements for detection of hematologic disorders, internal malignant diseases, or other systemic conditions associated with SS.
Adult↗
Chronic hepatitis C and skin diseases: a review.
OBJECTIVE: To emphasize the ongoing role of chronic hepatitis C virus (HCV) infection in the cause or exacerbation of severe dermatologic disorders. DESIGN: We present two case reports to outline the pertinent findings in hepatitis C-related cryoglobulinemia, leukocytoclastic vasculitis, and lichen planus and discuss the main disorders associated with chronic HCV infection. RESULTS: Chronic HCV infection has recently been recognized in association with various skin disorders. The most commonly reported association is the triad of leukocytoclastic vasculitis, cryoglobulinemia, and chronic HCV infection. Other cutaneous disorders associated with HCV infection include porphyria cutanea tarda, lichen planus, erythema nodosum, urticaria, erythema multiforme, and polyarteritis nodosa. CONCLUSION: Patients with onset or exacerbation of these disorders should undergo assessment for HCV infection.
Adult↗
The role of genetic variation in thiopurine methyltransferase activity and the efficacy and/or side effects of azathioprine therapy in dermatologic patients.
BACKGROUND: Thiopurine methyltransferase (TPMT) is one of three major enzymes involved in the metabolism of azathioprine and its active metabolite 6-mercaptopurine. Thiopurine methyltransferase activity is determined by an allelic polymorphism for either high (TPMTH) or low (TPMTL) enzyme activity. Homozygotes for the low activity allele are known to be at risk for profound myelosuppression with azathioprine. Heterozygotes may be at risk for myelosuppression. Homozygotes for the high activity allele may be inadequately immunosuppressed with conventional, empiric doses of azathioprine. We analyzed TPMT activity in red blood cell (RBC) lysates and determined the TPMT genotypes (based on normal population screening) of 28 dermatologic patients. This information was correlated with the observed efficacy and side effects of azathioprine therapy. OBSERVATIONS: Two patients with TPMT levels of less than 12.5 U/mL RBCs (both TPMTH heterozygotes) experienced leukopenia (white blood count < 4.0 x 10(9)/L) with azathioprine doses around 1.5 mg/kg. A third patient who experienced leukopenia had a TPMT level at the lower end of the homozygous range (15.5 U/mL RBCs) but received the highest dose of azathioprine (2.6 mg/kg) of all patients in this series. Ten patients with TPMT levels of more than 18.5 U/mL RBCs (all TPMTH homozygotes) receiving less than 1.5 mg/kg of azathioprine were judged to have a poor clinical response. In comparison, seven patients with TPMT levels between 12.5 and 18.5 U/mL RBCs (six TPMTH homozygotes and one TPMTH heterozygote) receiving 0.9 to 1.8 mg/kg of azathioprine had a favorable clinical response. Adverse effects of gastrointestinal upset and liver function test abnormalities did not appear to correlate with TPMT activity. CONCLUSION: The TPMTH heterozygotes may be at increased risk for myelosuppression with standard, empiric doses of azathioprine. On the other hand, homozygotes for TPMTH, particularly those with TPMT levels at the upper end of the homozygous range, may have a poor clinical response to azathioprine due to inadequate empiric dosing.
Adult↗
Cutaneous vasculitis.
Cutaneous vasculitis comprises a wide spectrum of clinical syndromes and histopathologic findings that share the common theme of vascular inflammation and blood vessel damage. Clinical pattern and proper histopathologic studies are essential to the proper classification and evaluation of vasculitis. This article discusses the major types of cutaneous vasculitis typified by necrotizing or leukocytoclastic vasculitis and includes discussions of Henoch-Schönlein purpura, urticarial vasculitis, erythema elevatum diutinum, cutaneous polyarteritis nodosa, livedoid vasculitis, and cutaneous granulomatous vasculitis.
Erythema↗
Home care: the next frontier of pediatric practice.
An overview of pediatric home care issues reveals the breadth and scope of services available to permit pediatricians to provide care at home. This care option has undergone explosive growth and represents one of the fastest-growing health expenditures. Paradoxically, direct physician involvement in the home has been limited during this expansion because of the way home care has been designed and organized with inadequate reimbursement for physician participation, and lack of awareness by, and education of, physicians concerning their roles and responsibilities. The rationale for physician involvement in home care includes the need for determination and reevaluation of the medical necessity of home care services. Future changes in health care delivery and payment will encourage even more consideration of alternative care sites. Physician participation in program and protocol design will facilitate and encourage the appropriate use of the home as a care setting. For the pediatrician to know about home care requires the development of a curriculum to be implemented in academic centers for physicians-in-training and in professional associations for continuing medical education. This curriculum should enable physicians to become primary participants in home care and should lead to research opportunities to evaluate the benefits of home care.
Child↗
Clinical evaluation of the macroduct sweat collection system and conductivity analyzer in the diagnosis of cystic fibrosis.
The purposes of this study were to compare sweat tests used in diagnosing cystic fibrosis (CF), as performed with the Macroduct collection system, with those utilizing the more laborious quantitative pilocarpine iontophoresis test (QPIT), and to ascertain the efficacy of the Sweat-Chek conductivity analyzer in eliminating some possibly unnecessary chloride analyses. A Macroduct sweat test was performed on one arm and a QPIT on the other on 1090 patients, 93 of whom had CF. Of these, 514 patients (43 with CF) also had a conductivity determination on the Macroduct sweat sample. All subjects were referred to the laboratory of one of us (K.B.H.) for sweat testing. Of the QPIT samples, 0.7% were inadequate, as were 6.1% of those from the Macroduct system. When sodium and chloride concentrations from the two tests were compared, the standard errors of the estimate were 3.90 and 3.85, respectively. Agreement within 8 mEq/L could then be expected with 95% confidence limits. With use of the Sweat-Chek analyzer, no patient with CF was found to have a conductivity of less than 90 mmol/L, whereas 430 (91%) of the non-CF subjects had a conductivity of less than 50 mmol/L. None of those 430 subjects had a sweat chloride value > 32 mmol/L. We conclude that the Macroduct collection system provides results equally as satisfactory as those provided by the QPIT and that the Sweat-Chek analyzer frequently eliminates the necessity of measuring chloride concentrations.
Adolescent↗
Ophthalmic findings in scleromyxedema.
PURPOSE: To catalog ophthalmic findings in a cohort of patients with scleromyxedema. METHODS: Thirty-five biopsy-proven patients with scleromyxedema evaluated at the Mayo Clinic in Rochester, Minnesota, from 1960 to 1991 were identified. Eye examinations were performed on 17 of the patients. Ophthalmic findings not attributable to other systemic or ocular disease were recorded. RESULTS: The following abnormalities were considered secondary to scleromyxedema: corneal opacities (2 patients), thickened eyebrow or eyelid skin (4 patients), lagophthalmos (1 patient), and ectropion (2 patients). One patient who had concurrent polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome also had choroidal folds and papilledema. A corneal biopsy in one patient disclosed deposits of acid mucopolysaccharide, consistent with one of two previously published cases. CONCLUSION: A series of patients with scleromyxedema was reviewed. This systemic disorder infrequently may cause visually significant ophthalmic manifestations, including eyelid changes and corneal deposits. Further study is needed to characterize better the nature of the corneal opacities.
Adult↗
Drug-induced linear IgA bullous dermatosis: report of six cases and review of the literature.
BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease that may be associated with drug exposure. OBJECTIVE: Our purpose was to compare the clinical, pathologic, and immunofluorescence findings in drug-induced LABD with those in the idiopathic type. METHODS: Six patients with an acute drug eruption were identified who had linear IgA deposition at the basement membrane zone (BMZ). Lesional tissue was examined by brightfield microscopy, and perilesional tissue was examined by direct immunofluorescence (DIF). The presence of circulating BMZ antibody was assayed by indirect immunofluorescence (IIF) on monkey esophagus (ME) and salt-split human skin (SS). RESULTS: Histopathologic examination showed subepidermal bullae with varying numbers of inflammatory cells. DIF showed linear IgA at the BMZ; three of the patients also had weak deposition of C3 at the BMZ. Serum from five patients was studied by IIF. One patient had circulating IgA BMZ antibodies in a titer of 1:80 on ME, localized to the dermal side on SS. All patients were free of lesions within 5 weeks after discontinuation of the drug. CONCLUSION: Drug-induced LABD is a self-limited eruption characterized by linear deposition of IgA without IgG at the BMZ. Most patients lack circulating antibodies. The distribution of lesions and the course of the disease differ from those of idiopathic LABD.
Aged↗
Lymphomatoid papulosis: a clinical and histopathologic review of 53 cases with leukocyte immunophenotyping, DNA flow cytometry, and T-cell receptor gene rearrangement studies.
BACKGROUND: Lymphomatoid papulosis (LyP) is a recurrent hemorrhagic papular skin eruption with a clinically benign course and histopathologic features of lymphoma. OBJECTIVE AND METHODS: To better characterize this disease, we studied 53 patients seen since 1965. RESULTS: A lymphoproliferative malignancy developed within 2 to 36 years after onset of LyP in eight patients. Histologically, the dermis in LyP showed an infiltrate of large (type A) or small (type B) atypical lymphocytes. The large atypical cells (type A) stained with CD30 (Ber-H2). Seven of the patients in whom lymphoma developed had type A histologic features. DNA flow cytometry showed mainly a diploid pattern, except for two cases that showed aneuploidy. Five of 11 patients showed T-cell receptor (TCR) clonal gene rearrangements; lymphoma has not developed in these patients. One patient had a TCR rearrangement in a plaque of mycosis fungoides but not in the LyP lesion. CONCLUSION: LyP is either a reactive skin condition or a localized lymphoid malignancy. Neither DNA flow cytometry nor TCR gene rearrangement can predict the 15% to 19% of patients in whom a lymphoma will develop. Continued observation of all patients is essential.
Adult↗
Lipomembranous (membranocystic) changes associated with morphea: a clinicopathologic review of three cases.
Lipomembranous (membranocystic) changes represent a distinctive form of pathology in adipose tissue. Although first described in the rare neurodegenerative disorder now called Nasu-Hakola disease, this change has also been observed in a variety of relatively common inflammatory and noninflammatory dermatoses. We report three cases of morphea associated with marked lipomembranous (membranocystic) changes in the subcutaneous adipose tissue.
Adipose Tissue↗
Cutaneous Wegener's granulomatosis: clinical, histopathologic, and immunopathologic features of thirty patients.
BACKGROUND: Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous inflammation and vasculitis. Its cutaneous manifestations vary. OBJECTIVE: We reviewed and characterized the clinical, pathologic, and immunopathologic features of the specific cutaneous manifestations of WG and investigated the sensitivity and the specificity of anti-neutrophilic cytoplasmic antibody (c-ANCA) in the cutaneous manifestations of this disease. METHODS: A retrospective analysis was conducted of 244 cases of WG observed between 1988 and 1992. RESULTS: Skin involvement occurred in 14% of the patients and was more frequent in generalized WG. Skin lesions may be an early premonitory sign of renal disease. Necrotizing ulcerations resembling pyoderma gangrenosum were not uncommon. Leukocytoclastic vasculitis was the most common cutaneous pathologic pattern. Findings of c-ANCA were positive in 81% of patients with cutaneous WG. CONCLUSION: Skin involvement usually occurred at presentation with generalized disease. c-ANCA is a valuable adjunct to diagnosis and follow-up of WG.
Adolescent↗
The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation.
Cutaneous granulomatous vasculitis is an uncommon histopathologic finding that has been associated with lymphoproliferative disorders, systemic vasculitis, autoimmune inflammatory diseases, and infection. To define further the concept of cutaneous granulomatous vasculitis and to emphasize its clinical importance, we reviewed biopsy material from 8 patients seen from 1985 through 1992. All biopsies showed evidence of blood vessel damage with fibrinoid change or hemorrhage (or both) and granulomatous inflammation in and around vessel walls. Special stains for microorganisms were negative in all cases. Associated medical disorders included neuropathy (2 patients), sarcoid-like disease (2), systemic vasculitis (1), lymphoma and suspected lymphoma (1 each), and associated herpes simplex virus (1). T-cell gene-rearrangement studies were negative in a patient with suspected lymphoma. Granulomatous cutaneous vasculitis is most commonly associated with lymphoma and systemic vasculitis. In selected cases, infection should be considered as an underlying cause.
Aged↗
Blepharochalasis associated with dermatomyositis and acute lymphocytic leukemia.
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Child, Preschool↗
Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients.
BACKGROUND: Erythema elevatum diutinum is a rare condition representing a chronic leukocytoclastic vasculitis. OBJECTIVE: Clinical and laboratory features of the disease were reviewed to better understand the disease. METHODS: The medical records and histopathologic slides of 13 patients with erythema elevatum diutinum were studied. RESULTS: The lesions were violaceous, deep red, or brown and typically were papules or plaques. Lesions were most often located on the extensor surfaces of the extremities. Associated medical problems included hematologic abnormalities in six patients: IgA clonal gammopathies (four), multiple myeloma (one), and myelodysplasia (one). Erythema elevatum diutinum preceded the myeloproliferative disorders by an average of 7.8 years. All patients showed vasculitis. Leukocytoclasia was present in 27 of 35 specimens. The predominant cell type in the inflammatory infiltrate was polymorphonuclear leukocytes or a mixture of polymorphonuclear leukocytes and lymphocytes. CONCLUSION: The most significant finding of this study is the association of erythema elevatum diutinum with hematologic disease, most frequently an IgA monoclonal gammopathy.
Adult↗