Transient acantholytic dermatosis induced by recombinant human interleukin 4

Mahler, Susan J.; Villez, Richard L. De; Pulitzer, Donald R.

doi:10.1016/0190-9622(93)70169-t

Cited by 43 publications

(24 citation statements)

References 22 publications

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“…A review of the medications that these patients were taking did not show a clear pattern to suggest a catisal relationship. None of the patients was noted to have taken recombinant interleukin 4 (5).…”

Section: Resultsmentioning

confidence: 99%

“…Since Grover first described transient acantholytic dermatosis in 1970 (1), there has been much speculation, but little consensus, as to the pathogenic mechanism of the disease. Ultraviolet radiation (1,2), heat and excessive sweating (3,4), drugs (5), infection (6) and malignancy (7-10) have all been associated with the disease; some of these have been implicated as instigating factors.…”

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confidence: 99%

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Grover's disease (transient acantholytic dermatosis): relationship of acanthoiysis to acrosyringia

et al. 1998

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Transient acantholytic dermatosis is often associated with excessive sweating, fever, and bed confinement. The pathogenesis of this disease has been postulated to be poral occlusion of damaged eccrine intraepidermal ducts. Histological and immunohistochemical and ultrastructural studies were performed on 10 biopsies from 10 patients with transient acantholytic dermatosis. Immunoreactions for carcinoembryonic antigen and cytokeratin-7 to identify eccrine duct epithelium were performed on all 11 biopsies. In addition, 5 of the biopsies were immunoreacted for cytokeratin 8. All immunoreactions were reviewed independently by two observers to determine extent of reactivity and whether it correlated with areas of epidermal acantholysis. Among the 11 biopsies, 8 showed acantholysis not associated with eccrine duct outflow tracts. In 2 biopsies the acantholysis was consistently associated with acrosyringea; in one case acantholysis was inconsistently associated with eccrine outflow tracts. Epidermal acantholysis in patients with Grover's disease is associated with the outflow tracts of eccrine ducts in a subgroup of patients. Although leakage of sweat from occluded sweat ducts in acrosyringia may be the mechanism operating in a subgroup of patients with Grover's disease, this does not appear to be the subgroup of patients in whom Grover's disease develops in the setting of being bedridden and/or sweating.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Grover's disease (transient acantholytic dermatosis): relationship of acanthoiysis to acrosyringia

et al. 1998

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“…[209] Eruption was closely related to the time of IL-4 administration, gradually resolved several days after discontinuation and reappeared soon after a further IL-4 course in 2 patients. This cutaneous eruption was not clearly related to fever, and an effect mediated by the production of plasminogen activator or a putative antibody-mediated mechanism were suggested.…”

Section: Interleukin-4 (Il-4)mentioning

confidence: 94%

Clinical Toxicity of Cytokines Used As Haemopoietic Growth Factors

1995

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A number of cytokines are used as haemopoietic growth factors and this review focuses on toxicities associated with granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1, IL-3, IL-4, IL-6 and macrophage colony-stimulating factor (M-CSF). Both GM-CSF and G-CSF, currently approved for clinical use, are generally well tolerated by the majority of patients during short term administration. Constitutional symptoms and bone pain are the most frequently reported adverse effects, but they are rarely treatment-limiting. Reactivation of rheumatoid symptoms, and exacerbation of autoimmune thyroiditis or autoimmune haematological disorders have sometimes been described. Severe cardiovascular complications include the possibility for arterial thromboses and the vascular leak syndrome, which is more specifically observed with GM-CSF. Reports of several cases and small series of patients have suggested that growth factors might increase the pulmonary toxicity of chemotherapy, a possibility that remains debated and requires further attention. Generalised or local cutaneous reactions are frequently noted with GM-CSF. Leukocytoclastic vasculitis was observed with both growth factors, while neutrophilic dermatoses have been mostly described with G-CSF. Exacerbation of psoriasis and isolated anaphylactic reactions have appeared with GM-CSF and G-CSF. The hepatotoxic potential of the growth factors is not clearly established, but the occurrence of coagulation abnormalities has recently been reported. Renal and biological disturbances are usually transient. Long term treatment with GM-CSF and G-CSF also seems to be well tolerated, but the possible occurrence of several adverse events, i.e. bone disorders, leukaemia, unmasking or acceleration of underlying disease, require further investigation in patients receiving prolonged treatment, as in myelodysplasia. Finally, antibodies against growth factors have been reported only with GM-CSF. Other cytokines are still under investigation. Flu-like and constitutional symptoms, sometimes dose-limiting, have been reported with IL-1, IL-3, IL-4 and IL-6, while M-CSF was occasionally associated with such adverse effects. More specific adverse events, also frequently considered as dose-limiting toxicities, include hypotension with IL-1, severe headache or skin rash with IL-3, and nasal congestion and gastroduodenal lesions with IL-4. Severe capillary leak syndrome has been reported only with IL-4. M-CSF toxicity is minimal and limited to reversible but sometimes dose-limiting thrombocytopenia and ophthalmological symptoms with the recombinant product. Again, the safety of long term administration of these cytokines has not yet been determined, and IL-3-induced disease progression in myelodysplastic patients has been suggested.

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“…IL-3 Therapie bei Patienten nach Chemotherapie führte in einigen Fällen zu Urtikaria, peripheren Ödemen und Flush (8). Eine transiente akantholytische Dermatose (M. Grover) wurde in mehreren mit IL-4 behandelten Patienten beobachtet (29). Periphere Ödeme sind nach IL-4 Injektion häufiger beobachtet worden (5).…”

Section: Andere Zytokineunclassified

Cutaneous side effects of clinically relevant cytokine therapies

Trefzer

Hofmann²,

Sterry³

2003

Dtsch med Wochenschr

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Zytokine sind eine heterogene Familie von kleinen, löslichen Proteinen, deren Aktion über spezifische Rezeptoren vermittelt wird. Mit dieser Rezeptorbindung werden über eine komplizierte Signalkaskade bestimmte Proteinkinasen phosphoryliert und somit aktiviert. Dadurch bilden sich Komplexe so genannter STAT-Proteine und anderer zytoplasmatischer Proteine. Diese Komplexe dringen in die Kerne ein und aktivieren über die Bindung an DNA-Sequenzen ein breites Spektrum von Genen. Zytokine sind sehr potente Moleküle, die im nanomolaren oder picomolaren Bereich Einfluss haben auf Zellproliferation, Zelldifferenzierung, Leukozytenmigration und -funktion, die Zahl hämatopoetischer Zellen, Temperaturregulation, Akute-Phase-Reaktionen und Zellüberleben (25). Auf manche Zellen wirken Zytokine als Induktoren von Zytokinen. Letztere können hierbei für eine therapeutische Wirkung verantwortlich sein, aber auch eine wichtige Rolle bei den Nebenwirkungen (NW) spielen. Neben zahlreichen Zytokin-induzierenden Faktoren gibt es auch Mediatoren, die eine Zytokinwirkung bzw. Zytokingenexpression hemmen können. Der klassische Inhibitor sind hierbei Glucocorticoide, die entsprechend als Immunsuppressiva und antiinflammatorische Wirkstoffe eingesetzt werden können. Manche Zytokine wirken auch als Inhibitoren der Synthese anderer Zytokine. So hemmt beispielsweise IL-10 die Produktion von TNFα und IL-1 in Monozyten. Weil sie das Wachstum von individuellen Zellen modifizieren und das Immunsystem durch die Wechselwirkung mit anderen physiologischen Systemen beeinflussen, sind Zytokine in eine Vielzahl von sowohl physiologischen als auch pathophysiologischen Prozessen involviert (13). Dies ist dadurch zu erklären, dass alle Zytokine pleiotrop wirken, d.h. über die Rezeptorbindung verschiedenste Aktivitäten in ihren Zielzellen vermitteln.Zytokine werden in verschiedene Klassen eingeteilt. Es werden hierbei Interleukine, Interferone, Wachstumsfaktoren und die Mitglieder der TNF-Familie unterschieden (Tab.1). Zytokine verfügen als körpereigene Proteine über einen hohen therapeutischen Wert, auch für Hauterkrankungen. Entsprechend werden zahlreiche Zytokine bei Malignomen, Hauterkrankungen oder anderen systemischen Erkrankungen klinisch eingesetzt (4), während sich andere noch in der klinischen Erprobung befinden.Wegen der Kurzlebigkeit der Zytokine sind zur Behandlung in der Regel relativ hohe Dosen notwendig. Die Verwendung rekombinanter Zytokine bietet Vorteile durch die Kontrolle der Blutkonzentrationen und der biologischen Aktivität, die durch die Zytokine induziert werden können. Hier sollen die vielfältigen kutanen Nebenwirkungen (NW) der bereits klinisch angewendeten Zytokintherapien besprochen werden. Eine Vielzahl weiterer Zytokine sowie anti-Zytokintherapien befinden sich noch im experimentellen Stadium des klinischen Einsatzes mit entsprechend wenigen Informationen über das Nebenwirkungsprofil. kurzgefasst: Zytokintherapien erlangen immer größere Bedeutung. Durch die zunehmende klinische Anwendung nimmt die Anzahl an berichteten Nebenwi...

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Transient acantholytic dermatosis induced by recombinant human interleukin 4

Cited by 43 publications

References 22 publications

Grover's disease (transient acantholytic dermatosis): relationship of acanthoiysis to acrosyringia

Grover's disease (transient acantholytic dermatosis): relationship of acanthoiysis to acrosyringia

Clinical Toxicity of Cytokines Used As Haemopoietic Growth Factors

Cutaneous side effects of clinically relevant cytokine therapies

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