[Hyperpigmentation of the abdominal skin. Diagnosis: Morbus Gougerot-Carteaud PCR].
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Abdominal Wall↗
Biomedical subjects
T Hunziker
Publications and source records attributed to T Hunziker.
[Pemphigoid nodularis triggered by hypereosinophilic syndrome?].
Pemphigoid nodularis (PN) is a rare clinical variant of pemphigoid characterized by prurigo-like skin lesions and antibodies against BP180 and BP230 characteristic for bullous pemphigoid. Interestingly, most PN patients never develop blisters. This condition is often resistant to treatment. We describe a female patient who was initially diagnosed with hypereosinophilic dermatitis. Later on, in the presence of eosinophilic infiltrations in the gastrointestinal tract, obstructive ventilation disorder, pericardial and pleural effusions, the diagnosis of idiopathic hypereosinophilic syndrome was made. During the following 3 years she developed recalcitrant PN.
Aged↗
Grover's disease induced by cetuximab.
A 71-year-old man exhibited an acute acneiform rash affecting the face and the upper trunk about 2 weeks after starting cetuximab, an epidermal growth factor (EGF) receptor antagonist treatment for metastatic colon cancer. The skin eruption faded after stopping cetuximab and applying topical corticosteroids. The reexposure to cetuximab 3 weeks later provoked a more extended relapse of the skin rash, which then clinically and histologically corresponded to transient acantholytic dermatosis . While the acneiform cutaneous side effects of the EGF receptor antagonists are interpreted as a result of the direct interference with pilosebaceous follicle homeostasis, in this case an acrosyringium-related pathogenesis might be postulated. Applying topical corticosteroids and emollients, the cetuximab therapy could be pursued.
Acneiform Eruptions↗
[Autologous cultured skin substitutes].
Progress in cell culture and biomaterial technologies has resulted in commercially available autologous and allogeneic skin substitutes that are composed of keratinocytes and/or fibroblats, in part combined with allogeneic (fibrin) or xenogeneic (collagen, hyaluronan) matrix substances. So far, clinical testing of tissue-engineered products focused on chronic wounds (vascular leg ulcers, diabetic foot ulcers); another major indication, however, is large acute skin defects (burns). During the last decade, partly-controlled clinical trials have been performed with several cultured skin substitutes, studying primarily vascular leg ulcers; a few of these products have been approved for defined indications by the regulatory authorities of various countries. To fulfill regulatory requirements and be eligible for reimbursement, safety as well as cost-effectiveness have to be documented for these novel therapies in contrast to established methods for clearly defined clinical settings; this, in combination with restricted health care resources, is actually hampering the clinical breakthrough of tissue engineering in the treatment of skin wounds, despite undiminished research activities.
Animals↗
Successful treatment of chemotherapy-refractory Sézary syndrome with alemtuzumab (Campath-1H).
INTRODUCTION: Sézary syndrome (SS) is a cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical T cells. Median survival after diagnosis is 10 yr, with chemotherapy resistance being a major problem in advanced disease. Alemtuzumab (Campath-1H) is a monoclonal antibody directed against the lymphocytic antigen CD52, expressed on B- and T-cells. Alemtuzumab is approved for relapsing chronic B-cell leukemia and seems to be active also in T-cell lymphomas such as T-cell prolymphocytic lymphoma, SS and mycosis fungiodes. CASE HISTORY: A 32-yr-old male patient presented with advanced stage, extensively pretreated SS with heavily itching erythroderma, peripheral lymphadenopathy, circulating Sézary cells and bone marrow infiltration. The disease had not responded to PUVA/interferon-alpha and progressed on chemotherapy with CHOP, 2-CDA, vinorelbine, etoposide and liposomal doxorubicin. Following treatment with alemtuzumab (30 mg i.v. three times per week for 10 wk), itching resolved rapidly and an almost complete remission was achieved within 3 months after starting this treatment. At 12-month follow up, no disease progression was present. CONCLUSION: In accordance with previous data, this single case underlines the potent activity of alemtuzumab in advanced, chemotherapy-refractory SS.
Adult↗
Progressive respiratory failure in paraneoplastic pemphigus associated with chronic lymphocytic leukemia.
A 70-year-old Caucasian man with chronic lymphocytic leukemia suffered from widespread, histologically proven cutaneous lichen planus responding to topical corticosteroids. 2 years later, he presented with painful erosive stomatitis and increasing dyspnea. Histology, direct and indirect immunofluorescence were diagnostic for paraneoplastic pemphigus. A full diagnostic workup could not disclose the cause of the progressive respiratory insufficiency. Despite aggressive treatment of the lymphocytic leukemia and the paraneoplastic pemphigus, the patient died 3 months after diagnosis. Paraneoplastic pemphigus may lead to pulmonary failure which is refractory to treatment and has a fatal outcome.
Aged↗
Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy.
BACKGROUND: Mastocytosis and/or elevated basal serum tryptase may be associated with severe anaphylaxis. OBJECTIVE: To analyse Hymenoptera venom-allergic patients with regard to basal tryptase in relation to the severity of sting reactions and the safety and efficacy of venom immunotherapy. METHODS: Basal serum tryptase was measured in 259 Hymenoptera venom-allergic patients (158 honey bee, 101 Vespula). In 161 of these (104 honey bee, 57 Vespula), a sting challenge was performed during venom immunotherapy. RESULTS: Nineteen of the 259 patients had an elevated basal serum tryptase. Evidence of cutaneous mastocytosis as documented by skin biopsy was present in 3 of 16 patients (18.8%). There was a clear correlation of basal serum tryptase to the grade of the initial allergic reaction (P<0.0005). Forty-one of the 161 sting challenged patients reacted to the challenge, 34 to a bee sting and 7 to a Vespula sting. Thereof, 10 had an elevated basal serum tryptase, i.e. 1 (2.9%) of the reacting and 2 (2.9%) of the non-reacting bee venom (BV) allergic individuals, as compared to 3 (42.9%) of the reacting and 4 (8%) of the non-reacting Vespula venom-allergic patients. Thus, there was a significant association between a reaction to the sting challenge and an elevated basal serum tryptase in Vespula (chi2=6.926, P<0.01), but not in BV-allergic patients. Systemic allergic side-effects to venom immunotherapy were observed in 13.9% of patients with normal and in 10% of those with elevated basal serum tryptase. CONCLUSIONS: An elevated basal serum tryptase as well as mastocytosis are risk factors for severe or even fatal shock reactions to Hymenoptera stings. Although the efficacy of venom immunotherapy in these patients is slightly reduced, most of them can be treated successfully. Based on currently available data, lifelong treatment has to be discussed in this situation.
Adolescent↗
Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development.
Although numerous chemokines act on monocytes, none of them is specific for these cells. Here, we show that breast and kidney-expressed chemokine (BRAK) is a highly selective monocyte chemoattractant. Migration efficacy and Bordetella pertussis toxin-sensitive Ca(2+) mobilization responses to BRAK were strongly enhanced after treatment of monocytes with the cyclic AMP-elevating agents prostaglandin E(2) and forskolin. BRAK is the first monocyte-selective chemokine, as other types of blood leukocytes or monocyte-derived dendritic cells and macrophages did not respond. Expression in normal skin keratinocytes and dermal fibroblasts as well as lamina propria cells in normal intestinal tissues suggests a homeostatic rather than an inflammatory function for this chemokine. In addition, macrophages were frequently found to colocalize with BRAK-producing fibroblasts. We propose that BRAK is involved in the generation of tissue macrophages by recruiting extravasated precursors to fibroblasts, which are known to secrete essential cytokines for macrophage development.
Cell Differentiation↗
Muckle-Wells syndrome?
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Diagnosis, Differential↗
[Eosinophilic fasciitis (Shulman syndrome)].
We report on a 35-year-old female with eosinophilic fasciitis (Shulman's syndrome). The characteristic features of this disease are scleroderma-like skin indurations, predominantly on the extremities, with joint contractures and intermittent blood eosinophilia. Histologic findings include fibrosis of muscle fascia and eosinophilic infiltration. Systemic corticosteroid therapy usually results in remission of symptoms. In this case refractory to systemic corticosteroids, we report for the fist time a successful therapy using cyclophosphamide.
Adult↗
IgG, IgA and IgE autoantibodies against the ectodomain of BP180 in patients with bullous and cicatricial pemphigoid and linear IgA bullous dermatosis.
BACKGROUND: Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. OBJECTIVES: We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. METHODS: Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180. RESULTS: All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180. CONCLUSIONS: The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures.
Adult↗
IgG autoantibodies from bullous pemphigoid patients recognize multiple antigenic reactive sites located predominantly within the B and C subdomains of the COOH-terminus of BP230.
Bullous pemphigoid is a subepidermal bullous disorder characterized by an autoantibody response against the bullous pemphigoid antigen 230 (BP230) and the bullous pemphigoid antigen 180 (BP180), a cytoplasmic component and a transmembrane component, respectively, of hemidesmosomes. Although immunodominant sequences within the extracellular domain of BP180 have been identified, characterization of the antigenic sites on BP230 is still incomplete. To identify autoantibody-reactive sites on BP230 and to examine whether the targeted regions are contained within functionally important domains, recombinant fragments encompassing almost the entire BP230 were used to assess the reactivity of 25 bullous pemphigoid sera by immunoblotting. Our results demonstrate that (i) the region bearing the B and C subdomains of the COOH-terminus of BP230 contains immunodominant sequences recognized by the majority of bullous pemphigoid sera; (ii) additional autoantibody- reactive sites are present over extended regions of the NH2-terminal half of BP230 without evidence for antigenic cross-reactivity between the NH2- and COOH-termini of BP230; and, finally, (iii) autoantibodies reacting with the BP230 tail predominantly belong to the IgG4 and IgG1 subclasses, suggesting that both autoreactive TH2 and autoreactive TH1 cells regulate the autoantibody response to immunodominant sequences of BP230. As the COOH- terminus of BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque, whereas its NH2-terminus contains sequences important for its interaction with other constituents of hemidesmosomes, autoantibodies to BP230 might precipitate subepidermal blister formation and perpetuate the disease not only by eliciting an inflammatory reaction but also by interfering with the function of BP230 and thus the stability of hemidesmosomes.
Aged↗
Tumorlike eosinophilic granuloma of the skin.
In 1952, Kuske reported on a patient with a peculiar tumor on the dorsum of the right hand; histological analysis revealed a dense dermal infiltrate with numerous eosinophils. Not aware of any similar case report in the literature, he coined the descriptive term "tumor-like eosinophilic granuloma of the skin." In 1995, a 55-year-old white man with cancer of the prostate presented with a 4-month history of two reddish-brown, solid skin tumors on his left forearm and on the right side of his abdomen, respectively. Histologic examination revealed a dense, superficial and deep, tumorlike dermal inflammatory infiltrate consisting mainly of eosinophils as well as neutrophils and in part epithelioid, in part foamy histiocytes. Flame figures were absent. Immunohistochemical analysis was negative for S-100 protein, whereas sporadic cells in the infiltrate were CD1a positive and many mononuclear-histiocytic cells reacted with MAC 387. Stains as well as cultures for bacteria, mycobacteria, and fungi were negative. The descriptive diagnosis of tumorlike eosinophilic granuloma of the skin was made. Seven weeks after prostatectomy, both tumors resolved spontaneously and so far has not recurred. In our opinion, this is the second report of Kuske's tumorlike eosinophilic granuloma of the skin. Perhaps tumorlike eosinophilic granuloma of the skin, eosinophilic ulcer of the mucosa, and transient eosinophilic nodulomatosis should be considered a mucocutaneous reaction pattern as is seen in cats. In humans, hypersensitivity reactions or atopy could emerge as an etiological link.
Adenocarcinoma↗
[Maculopapular exanthema: should suspected drugs continue to be used?].
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Drug Monitoring↗
Human melanocytes grown in epidermal equivalents transfer their melanin to follicular outer root sheath keratinocytes.
Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred "through racial barriers". Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.
Biological Transport↗
Pmg-1 and pmg-2 constitute a novel family of KAP genes differentially expressed during skin and mammary gland development.
The epidermis, by invagination of the undifferentiated ectodermal cells, gives rise to several distinct structures including hair, sebaceous, eccrine sweat and mammary glands. We have recently isolated a novel gene, pmg-1, expressed in the pubertal mouse mammary gland. While investigating its genomic structure, we identified a related gene in close proximity, which we have termed pmg-2. pmg-1 and pmg-2 are intron-less, are transcribed in opposite directions and are separated by a potential promoter region of 2.8 kb containing putative binding motifs for the developmental transcription factors Lef-1, Sox5 and D-STAT. pmg-1 and pmg-2 encode small proteins rich in G, S, F, Y and Q and contain characteristic repeats reminiscent of the keratin-associated proteins (KAPs). Both genes are expressed in growing hair follicles in skin as well as in sebaceous and eccrine sweat glands. Interestingly, expression is also detected in the mammary epithelium where it is limited to the onset of the pubertal growth phase and is independent of ovarian hormones. Their broad, developmentally controlled expression pattern, together with their unique amino acid composition, demonstrate that pmg-1 and pmg-2 constitute a novel KAP gene family participating in the differentiation of all epithelial cells forming the epidermal appendages.
Amino Acid Sequence↗
Drug-induced linear IgA bullous dermatosis associated with ceftriaxone- and metronidazole-specific T cells.
BACKGROUND: Previous reports indicate that various drugs may induce linear IgA bullous dermatosis (LABD). The role of T cells and T-cell-derived cytokines in the pathomechanism of such skin lesions, however, has remained unclear. OBJECTIVE: To describe a case of LABD induced by ceftriaxone and metronidazole in an 80-year-old female suffering from cholelithiasis with concomitant cholecystitis and provide evidence that drug-specific T cells and their cytokines may contribute to the development of LABD lesions. METHODS: We performed flow cytometry analysis of peripheral blood T cells during LABD, epicutaneous testing (scratch-patch) and lymphocyte proliferation analysis (LTT) with the suspected drugs, routine histological and immunohistochemical examination of the acute skin lesions during LABD as well as of the positive epicutaneous test reactions and measurement of cytokines (IL-4, IL-5, IL-10, TNF-alpha, IFN-gamma) in the supernatant of the LTT cultures. RESULTS: An increased number mainly of activated CD8+ cells was detected in the peripheral blood during LABD. T cell sensitization to ceftriaxone and metronidazole was confirmed by epicutaneous testing and LTT, indicating that these methods may be useful in identifying the causative drugs. Enhanced cytokine levels, particularly of IL-5, were found in the supernatant of the LTT stimulated with ceftriaxone and metronidazole. Furthermore, in situ expression of IL-5 was confirmed in the patient's skin lesions by immunohistochemistry. CONCLUSION: Our findings suggest that in addition to IgA antibodies drug-specific T cells and their subsequent release of cytokines may play an important role in the pathogenesis of drug-induced LABD.
Aged↗
Cultured keratinocyte grafts.
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Biological Dressings↗