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PubMed2003

The sensitivity and specificity of "caterpillar bodies" in the differential diagnosis of subepidermal blistering disorders.

Caterpillar bodies are eosinophilic, elongated, segmented bodies located within the roofs of blisters and are considered to represent a specific histopathologic feature of porphyric bullous eruptions, including porphyria cutanea tarda and erythropoietic protoporphyria. The possibility that similar or identical bodies may be present in other disorders prompted further study exploring the specificity of caterpillar bodies in the differential diagnosis of subepidermal vesiculobullous disorders. Seventy-six cases exhibiting subepidermal clefting were reviewed by light microscopy. "Classic" caterpillar bodies were present in porphyria cutanea tarda (6 of 14) and 1 case representing either venous stasis-associated bulla or possibly bullosis diabeticorum. Caterpillar body-like clusters were present in porphyria cutanea tarda (5 of 14), erythropoietic protoporphyria (1 of 3), bullous pemphigoid (7 of 24), and junctional or dystrophic epidermolysis bullosa (3 of 5). In some cases, classic caterpillar body and caterpillar body-like clusters coexisted in a blister roof. Caterpillar bodies or caterpillar body-like clusters were not identified in any cases of dermatitis herpetiformis, linear IgA bullous dermatosis, bullous erythema multiforme, epidermolysis bullosa acquisita, or wound-healing reactions. In contrast to caterpillar bodies, caterpillar body-like clusters were negative for PAS or Type IV collagen stains. In conclusion, caterpillar bodies appear to represent a specific feature of porphyria cutanea tarda (specificity, 98%) but were present in less than half of those cases in this study (sensitivity, 43%). Caterpillar body-like clusters are less specific and may be present in porphyria cutanea tarda, erythropoietic protoporphyria, pseudoporphyria, bullous pemphigoid, epidermolysis bullosa, and epidermolysis bullosa acquisita.

Adult↗
PubMed1991

GM-CSF as an alternative to dose modification of the combination zidovudine and interferon-alpha in the treatment of AIDS-associated Kaposi's sarcoma.

Combined zidovudine (ZDV) and interferon-alpha (IFN) is an appealing therapy for AIDS-associated Kaposi's sarcoma because of the antiretroviral as well as antitumor potential of this combination. Overlapping myelotoxicity of these agents, however, frequently complicates their clinical use. This phase I/II study was undertaken to test the safety and efficacy of granulocyte-macrophage colony stimulating factor (GM-CSF) in those patients who became neutropenic while receiving ZDV (1,200 mg/day) and IFN (9 MU/day). Despite a "high-risk" population of patients, the tumor response rate among evaluable patients was 50% (33% overall). Sixty-four percent of patients required GM-CSF and all patients receiving GM-CSF had a prompt improvement in their absolute neutrophil count (ANC). The use of GM-CSF was associated with an improved end of study ANC (p less than 0.05), but was not associated with tumor response, CD4 count improvement, or improved change in hemoglobin concentration. GM-CSF/ZDV/IFN was not associated with increased toxicity over ZDV/IFN; however, two unusual events occurred in the GM-CSF/ZDV/IFN group: erythema multiforme and glucose intolerance. Dose-limiting thrombocytopenia and anemia were seen in two patients and anemia in one patient on GM-CSF/ZDV/IFN. No consistent alterations in serum HIV p24 antigenemia were noted in either group. The use of GM-CSF mitigated the neutropenia of combined ZDV and IFN. Further study evaluating the utility of this hematopoietic growth factor in combination therapies for AIDS patients is warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The complications of dermal tattooing.

Dermal tattooing has been performed for over 4,000 years. Some of the reported complications from tattooing include pyogenic infections, viral hepatitis, syphilis, tuberculosis cutis, rubella, herpes simplex, herpes zoster, psoriasis, lichen planus, lupus, pigment allergy and sensitivity, keloids, sarcoidal granulomas, erythema multiforme, malignant melanoma, squamous cell carcinoma, and basal cell carcinoma. Most complications can be avoided by utilizing proper aseptic technique and avoiding exotic pigments. A survey of the members of the American Society of Ophthalmic Plastic and Reconstructive Surgery was taken to determine the prevalence of eyelid tattooing and complications encountered. The findings of this survey are presented.

Coloring Agents↗
PubMedDate not supplied

Management of severe toxic epidermal necrolysis in children.

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme that results in extensive epidermal sloughing; the condition is associated with a mortality of up to 70%. From 1991 to 1998, 10 children with severe toxic epidermal necrolysis were referred to a regional pediatric burn facility. Wounds were managed with strategy involving prevention of wound desiccation and superinfection, including the frequent use of biologic wound coverings. Children unable to guard their airway because of extensive oropharyngeal involvement were prophylactically intubated. Enteral nutrition was stressed. Steroids were not used and antibiotics were administered to managed specific foci of infection only. The 2 boys and 8 girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years) and sloughed surface area of 76+/-6% of the body surface (range 50 to 95%). Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were felt to have triggered the syndrome. Six children (60%) required intubation for an average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal involvement occurred in 9 (90%) and ocular involvement in 9 (90%). Although infectious complications were common (2 pneumonias, 2 urinary infections, 1 bacteremia, 2 central line infections, and 2 candidemias), all children survived after lengths of stay in the burn unit averaging 19+/-3 (range 6 to 40) days. The most common long-term morbidity was keratitis sicca (2 children, 20%), finger nail deformities (3 children, 30%), and variegated skin pigment changes (5 children, 50%). Although having both a cutaneous and visceral wound that predispose them to infectious complications, most children with TEN will survive if managed with a strategy emphasizing biologic wound closure, intensive nutritional support, and early detection and treatment of septic foci. Burn units have the resource set required to manage severe TEN and early referral of such children may have a favorable impact on survival.

Adolescent↗
PubMed1997

Adverse reactions to trimethoprim-sulfamethoxazole among children with human immunodeficiency virus infection.

BACKGROUND: The clinical course of HIV infection is frequently different among infants and children from that in adults. In adults among the most common sources of morbidity related to therapy are adverse drug reactions, notably to trimethoprim-sulfamethoxazole. Although there are case reports of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection, the precise rate and clinical characteristics of these adverse reactions among HIV-infected children are unknown. METHODS: We reviewed the clinical records of all children referred to a regional HIV clinic in a 6-year period. Therapy and suspected adverse drug reactions to therapy were reviewed by one of the investigators not involved in patient care. Adverse drug reactions were identified and characterized according to previously established criteria. RESULTS: During this time 78 children were referred for assessment of possible HIV infection, 45 of whom were ultimately determined to have the infection. Twenty-five were treated with trimethoprim-sulfamethoxazole, 15 (60%) of whom tolerated therapy and 10 (40%) of whom had adverse reactions. The most common type of adverse reaction was erythema multiforme (70%), followed by neutropenia (20%) and Stevens-Johnson syndrome (10%). In two patients a serious adverse reaction to trimethoprim-sulfamethoxazole led to the diagnosis of HIV infection. CONCLUSIONS: The overall incidence and type of serious adverse reactions to trimethoprim-sulfamethoxazole among infants and children with HIV infection appear to be similar to those among adults.

Anti-Infective Agents↗
PubMed1983

Chronic bullous dermatosis of childhood.

Chronic blistering dermatosis of childhood (CBDC) in a 1-year-old black girl responded to the administration of sulfapyridine. CBDC is a rare blistering skin disease characterized by the presence of tense bullae and the linear deposition of IgA at the dermal-epidermal junction of lesional and perilesional skin. The disease may resemble bullous impetigo, bullous erythema multiforme, dermatitis herpetiformis, or pemphigus. The treatment involves the use of either dapsone or sulfapyridine.

Chronic Disease↗
PubMed2005

Human immunodeficiency virus, pregnancy, and Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening dermatologic disorders that are more common in the setting of a compromised immune system. We present the case of a pregnant patient with known human immunodeficiency virus (HIV) infection who presented with Stevens-Johnson syndrome after treatment with antibiotics for a urinary tract infection. CASE: A young woman at 33 4/7 weeks of gestation with known HIV infection presented to the emergency room with a chief complaint of rash, fever, blisters, and lower abdominal pain. Her symptoms were present for 2 days after ingestion of nitrofurantoin, prescribed for a urinary tract infection. She was diagnosed with preterm labor and possibly Stevens-Johnson syndrome. Due to active labor, HIV, and vaginal stenosis, a primary cesarean was performed. A skin biopsy performed at the time of admission confirmed the diagnosis of a drug-induced dermatosis (erythema multiforme), evidenced by subepidermal bullae, hemorrhage, and acantolated, dyskeratotic eosinophilic cells. CONCLUSION: Stevens-Johnson syndrome and toxic epidermal necrolysis represent a spectrum of disease that has been long associated with multiple drugs, recently including many antiretroviral medications. It also seems that the incidence of these conditions is increased in immunocompromised patients. We speculate that the combination of HIV and pregnancy in addition to antibiotic treatment, such as with nitrofurantoin, may induce Stevens-Johnson syndrome in patients with severely altered immune systems.

Adrenal Cortex Hormones↗
PubMed1994

Expression of Fas antigen on keratinocytes in vivo and induction of apoptosis in cultured keratinocytes.

Fas antigen, which belongs to a nerve growth factor/tumor necrosis factor receptor superfamily, is a membrane protein that induces apoptosis. In humans, distribution of Fas antigen has been reported on cell lines and lymphocytes. Immunohistochemical studies revealed Fas antigen on the keratinocytes of lesional epidermis in lichenoid drug eruption, erythema multiforme, contact dermatitis, bullous pemphigoid, pemphigus vulgaris, and herpes zoster; it is co-expressed with intercellular adhesion molecule-1. Cultured keratinocytes expressing Fas antigen increased from 8.4% to 34.6% after stimulation with interferon gamma for 24 h. Treatment of interferon-gamma-stimulated keratinocytes with anti-Fas for 48 h resulted in DNA fragmentation and death of 32% of cells, suggesting that Fas antigen may mediate apoptosis. The expression of Fas antigen on keratinocytes in lesional skin suggests that death via Fas antigen may play an important role in the pathogenesis of keratinocyte cytotoxicity.

Antibodies↗
PubMed1992

A new method to measure type I and III collagen synthesis in human skin in vivo: demonstration of decreased collagen synthesis after topical glucocorticoid treatment.

Collagen is synthesized as procollagen and large extra domains known as propeptides are cleaved off enzymatically. In the present study we have measured the carboxyterminal propeptide of type I collagen (PICP) and the aminoterminal propeptide of type III collagen (PIIINP) in blister fluids of human skin. High concentrations of PICP were found in the spontaneous blisters of patients with bullous pemphigoid, erysipelas, or erythema multiforme. Detectable amounts were also found in suction blisters induced on healthy skin. Because the concentrations in suction blisters were several times higher than in corresponding serum, most of PICP and PIIINP was derived from the underlying dermis. This method was used for assessing type I and type III collagen synthesis after topical glucocorticoid treatment. Clobetasol-17-propionate (CP) decreased the concentrations of PICP by 75% after 1 d of treatment, the maximum inhibition (92%) being found after 2 d treatment. PIIINP was also affected. Hydrocortisone and hydrocortisone-17-butyrate also decreased the concentrations of PICP and PIIINP, but less markedly than CP. Partial recovery was seen 3 d after stopping the treatment. Thus measurement of collagen type specific propeptides in suction blisters can be used as an estimate of collagen synthesis in vivo, avoiding both local anesthesia and skin biopsing. With radioimmunoassays for PICP and PIIINP a large number of samples can also be processed simultaneously.

Administration, Topical↗
PubMed1988

Development of an in vitro keratinocyte model for use in the study of HSV specific cytotoxicity.

Herpes simplex virus (HSV) specific immune mediated cytotoxicity may be involved in control of HSV infections and in the tissue damage induced by HSV infection or HSV related skin disease such as herpes associated erythema multiforme. Developing an in vitro model to study this process has proved difficult due to the lack of an appropriate target cell that will express HSV antigens but is not simultaneously subject to viral induced cell death. The purpose of this study was to develop a model in which keratinocytes express cell surface HSV specific antigens but at the same time are protected from death due to viral infection. We found that keratinocytes infected with HSV in the presence of acyclovir (ACV) expressed such antigens yet remained viable for a period of time after the onset of antigen expression such that cytotoxicity studies could be successfully performed. Rabbit skin cells, a transformed keratinocyte line, or second passage human neonatal foreskin keratinocytes were grown in culture medium with or without 200 microM ACV and were infected with HSV. Examination by direct immunofluorescence with anti-HSV antibody revealed uniform HSV antigen expression by cells both with and without ACV by 8 h after infection. Cells infected without ACV exhibited marked structural abnormalities including formation of multinucleated giant cells, while cells with ACV showed fewer such changes throughout a 24-h period. An Ethidium Bromide-Acridine Orange cytotoxicity assay demonstrated significant increases in the cytotoxicity of infected cells not protected by ACV compared to that of cells with ACV (p less than .001). This in vitro model should prove useful in the investigation of HSV specific immune mediated cytotoxicity.

Acridine Orange↗
PubMed1990

Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets.

Immunologic cytotoxicity is an important endpoint of the immune response to tumors, viral infected cells, grafted tissues, and exogenous microorganisms, and is also an important mechanism of disease, especially in autoimmunity. There are multiple mechanisms of immunologic cytotoxicity, but each has three major stages: leukocyte/target attachment, specific recognition, and target lysis following effector activation. Adhesion molecules present on leukocytes and potential targets appear to be involved in all three stages of cytotoxicity. A major factor in all types of cellular cytotoxicity is the interaction of LFA-1 on leukocytes and CAM-1 on targets. Modulation of ICAM-1 levels on target by the cytokines TFN-g, IL-1, and TNF-a is a major point of control of the susceptibility of targets to cytotoxicity by many different cytotoxic mechanisms. It also appears that modulation of the avidity of LFA/ICAM-1 binding is another important control point in modulating immunologic cytotoxicity. Cytokines also have important effects on immunologic cytotoxicity in ways other than adhesion molecule induction: effector priming to better respond to specific recognition signals, effector mobilization into tissue, and expansion of cytotoxic effector populations. ICAM-1 on the surface of epidermal keratinocytes and melanocytes is likely to greatly influence cytotoxic damage of these cells in diseases as photosensitive lupus erythematosus, lichen planus, erythema multiforme, and vitiligo. It has been found that the epidermal staining pattern for ICAM-1 in each of these diseases in distinctive and different in each disease. It is proposed that disease-specific induction of ICAM-1 by factors such as UVR and herpes-virus is an important determinant in triggering these skin diseases and in determining the pattern of disease.

Cell Adhesion Molecules↗
PubMed2004

Sesquiterpene lactone mix patch testing supplemented with dandelion extract in patients with allergic contact dermatitis, atopic dermatitis and non-allergic chronic inflammatory skin diseases.

We investigated the value of patch testing with dandelion (Compositae) extract in addition to sesquiterpene lactone (SL) mix in selected patients. After we detected a case of contact erythema multiforme after patch testing with dandelion and common chickweed (Caryophyllaceae), additional testing with common chickweed extract was performed. A total of 235 adults with a mean age of 52.3 years were tested. There were 66 men and 169 women: 53 consecutive patients with allergic contact dermatitis (ACD); 43 with atopic dermatitis (AD); 90 non-atopics suffering from non-allergic chronic inflammatory skin diseases; 49 healthy volunteers. All were tested with SL mix 0.1% petrolatum (pet.) and diethyl ether extracts from Taraxacum officinale (dandelion) 0.1 and 3.0% pet. and from Stellaria media (common chickweed) 0.1 and 3% pet. A total of 14 individuals (5.9%) showed allergic reaction (AR) to at least 1 of the plant allergens, 4 (28.6%) to common chickweed extract, and 11 (78.6%) to Compositae allergens. These 11 persons made the overall prevalence of 4.7%: 8 (3.4%) were SL-positive and 3 (1.3%) reacted to dandelion extract. 5 persons (45.5%) had AD, 2 had ACD, 2 had psoriasis and 2 were healthy controls. The Compositae allergy was relevant in 8 cases (72.7%). The highest frequency of SL mix sensitivity (9.3%) was among those with AD. Half the SL mix-sensitive individuals had AD. ARs to dandelion extract were obtained only among patients with eczema. A total of 9 irritant reactions (IRs) in 9 individuals (3.8%) were recorded, 8 to SL mix and 1 to common chickweed extract 3.0% pet. No IR was recorded to dandelion extract (P = 0.007). Among those with relevant Compositae allergy, 50.0% had AR to fragrance mix and balsam of Peru (Myroxylon pereirae resin) and colophonium. SLs were detected in dandelion but not in common chickweed. Our study confirmed the importance of 1 positive reaction for emerging, not fully established, Compositae allergy. In conclusion, the overall prevalence of 4.7% in our study represents a basal SL mix detection rate of 3.4% reinforced and safely supplemented by testing with the dandelion extract.

Adolescent↗
PubMed2004

Statins: novel additions to the dermatologic arsenal?

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), atorvastatin, cerivastatin, fluvastatin, pravastatin, lovastatin and simvastatin, reduce atherogenesis and cardiovascular morbidity. Besides, there is growing evidence that statins have immunomodulatory activities. Statins downregulate the expression of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MAC-1) and lymphocyte function-associated antigen-1 (LFA-1), on leucocytes and endothelial cells and, through binding to LFA-1, interfere with ICAM-1-LFA-1 interaction, which is crucial for activation of lymphocytes by antigen-presenting cells, ingress of leucocytes into the inflammation sites and immunologic cytotoxicity. Statins inhibit the inducible expression of major histocompatibility complex class II in several cell types including macrophages and downregulate the expression of T-helper-1 (Th1) chemokine receptors on T cells, leading further to inhibition of activation of lymphocytes and their infiltration into the inflammation sites. Statins block the induction of inducible nitric oxide synthase and the expression of several proinflammatory cytokines such as tumour necrosis factor-alpha and interferon-gamma in macrophages and possess antioxidant effects. These agents inhibit the proliferation of immunocytes and the activation of natural killer cells. Regarding the above facts and in view of their safety and inexpensiveness, statins may prove invaluable in the treatment of a multiplicity of dermatologic disorders, especially those characterized by ingress of activated leucocytes into the skin, such as alopecia areata, vitiligo, lichen planus, subacute cutaneous lupus erythematosus, erythema multiforme, psoriasis, bullous pemphigoid, systemic sclerosis, mycosis fungoides, toxic epidermal necrolysis and Behcet's disease.

Humans↗
PubMed1990

Evaluation of skin test reactions in patients with non-immediate type drug eruptions.

Skin test reactions were evaluated in 242 patients who appeared to develop delayed type drug eruptions from the clinical course. The patch testing was positive in 62 (31.5%) of 197 patients tested and the intradermal testing in 105 (89.7%) of 117 patients. The positive ratios of intradermal testing were higher in maculopapular (MP), erythema multiforme (EM), and erythrodermic (ED) types than in eczematous (Ecz) type drug eruptions, while those of patch testing were comparatively high in ED, Ecz type, and anticonvulsant-induced drug eruptions. It is considered that the combination of patch testing and intradermal testing is useful for determination of causative drugs in delayed type drug eruptions.

Adolescent↗
PubMed1990

Histopathologic study of cutaneous lesions in Behçet's syndrome.

Light microscopic studies of 55 patients with complete and incomplete types of Behçet's syndrome were reviewed. We reported here 39 skin biopsies from 30 patients with cutaneous lesions of oral, and genital ulcers, folliculitis, erythema multiforme, and thrombophlebitis. Leukocytoclastic vasculitis was seen in 5 of 12 (42%) cases of oral ulcers and 2 of 7 (29%) of genital ones. Lymphocytic vasculitis was demonstrated in 3 of 12 (25%) cases of oral ulcers and 4 of 7 (57%) of genital ulcers. However, the vasculitis was observed only locally in the areas with moderate or severe inflammation. From the biopsy specimens of our cases with fully developed mucocutaneous lesions of Behçet's syndrome, it appears that the forms of vasculitis that are often emphasized in the literature are a phenomenon secondary to the intense inflammation seen in such cutaneous lesions.

Behcet Syndrome↗
PubMed1994

Pathogenesis of mucocutaneous lesions in Behçet's disease.

Behçet's disease (BD) is characterized by recurrent oral aphthae, skin lesions, eye lesions, and genital ulceration. To determine the pathogenesis of BD, we performed histological and immunohistochemical studies of these mucocutaneous lesions, an assay of neutrophil activity, and HLA typing. Dense dermal or subcutaneous infiltrations of polymorphonuclear cells (PMN) without leukocytoclastic vasculitis were found in 28 of 57 lesions. Immunohistochemically, deposits of C3 on the vessels were found in 12 of 31 lesions. Deposits of immunoglobulin were not found except for one of IgM. C3 deposits and PMN infiltrations were significantly related (p < 0.05). PMN activity by polarization was enhanced; however, the results did not show a significant relationship with the PMN infiltrations or the C3 deposits. The incidence of HLA-B51 was significantly high in BD, but no significant relationship was found between HLA-B51 and the results of other examinations. These results suggest that the pathogenesis of BD lesions differs from that of collagen diseases and that C3 deposits on the vessels may play an important role in the development of mucocutaneous lesions where PMN have mainly infiltrated.

Adolescent↗
PubMed2001

Acute hemorrhagic edema in a four-year-old Japanese boy.

A case of acute hemorrhagic edema (AHE), a unique form of leukocytoclastic vasculitis limited only to the skin, was seen in a four-year-old boy. It was characterized by an abrupt onset of fever, peripheral edema, and rosette-shaped purpuric plaques. Although the skin lesion might be confused clinically with other dermatoses such as Henoch-Schönlein purpura, Sweet's disease and erythema multiforme, his laboratory data were normal, and the disorder follows a benign course with spontaneous resolution within one week.

Acute Disease↗