Rim S. Ishak

Hypoxia-inducible factor in cancer angiogenesis: Structure, regulation and clinical perspectives

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations. In this paper, we review what has been described about HIF-1: its structure, its regulation and target genes, its role in cancer, and its implication for cancer therapy.

Penicillamine Revisited: Historic Overview and Review of the Clinical Uses and Cutaneous Adverse Effects

Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. These cutaneous adverse effects may correlate with the dosage and duration of penicillamine therapy as well as the disease being treated.

Non-Uremic Calcific Arteriolopathy (Calciphylaxis) in Relapsed/Refractory Hodgkin's Lymphoma: A Previously Unreported Association

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Cutaneous sarcoidosis: clinicopathologic study of 76 patients from Lebanon

Sarcoidosis is a multi‐system granulomatous disease of unknown etiology. The skin is involved in 25% of cases. Studies on cutaneous sarcoidosis from our region are lacking.

Vulvar pyoderma gangrenosum with renal involvement

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis of unknown etiology which usually occurs over the lower extremities; however, unusual presentations such as that involving the genital region have been described. Extracutaneous involvement of PG in the form of sterile neutrophilic infiltrates in various organs has infrequently been reported. We hereby describe a case of PG that was limited to the vulvar and perianal area in a 37-year-old female, with associated renal involvement in the form of a slight increase in the serum creatinine, microhematuria of glomerular origin and proteinuria. The patient had a rapid response of both her mucocutaneous lesions and renal dysfunction after the initiation of systemic steroids. The present case highlights the importance of evaluating all patients with PG for extracutaneous disease to avoid potentially harmful diagnostic or therapeutic procedures. Two other reasons for interest are the localized presentation of disease on the genital region and the presence of vascular involvement, albeit without signs of true vasculitis, vascular changes possibly being a histological hallmark of PG involving genitalia.

Successful treatment of hydroxyurea-associated chronic leg ulcers associated with squamous cell carcinoma.

Hydroxyurea (HU) is an antineoplastic drug used in the treatment of chronic myeloproliferative neoplasms (MPNs). HU is associated with cutaneous adverse effects, whereas severe complications such as leg ulcers and non-melanoma skin cancers (NMSCs) are rare and only observed after long-term treatment. We herein report a patient with essential thrombocythemia (ET) treated chronically with HU, and who developed refractory bilateral leg ulcers complicated by squamous cell carcinoma (SCC) over both heels. The patient was successfully managed by multiple debridement stages and skin grafting surgeries.

Hypopigmented papules on the upper trunk and forearm of a young man.

What is your diagnosis?

Successful Management of Hydroxyurea-induced Leg Ulcers in Essential Thrombocythemia: Report of 3 Cases.

Essential thrombocythemia is one of the myeloproliferative neoplasms with a plethora of thrombohemorrhagic complications. Hydroxyurea has been proven to be an effective treatment for this condition. However, it is not without side effects. We herein report 3 patients with essential thrombocythemia treated with hydroxyurea who developed refractory leg ulcers, and we outline their successful management. We also review the literature to shed light on the mechanism of this toxicity. Awareness of this important treatment complication is important to avoid the pitfall of futile invasive interventions.

Corticosteroid-Pulstherapie bei Alopecia areata: 10-Jahres-Langzeitergebnisse

Hintergrund: Zur Wirksamkeit der Corticosteroid-Pulstherapie bei Alopecia areata (AA) liegen nur wenige Daten vor. Ziel: Mit dieser Studie sollten die Langzeitergebnisse von Patienten unter Methylprednisolon-Bolustherapie untersucht werden. Methoden: In diese Studie wurden 60 Patienten eingeschlossen, die zwischen 1995 und 2000 eine Behandlung erhalten hatten. Die Kurzzeitergebnisse wurden im Jahr 2000 analysiert. Die Untersuchung der Langzeitergebnisse von 30 Patienten erfolgte 2010 mithilfe eines telefonischen Fragebogens. Ergebnisse: Bei 10/30 Patienten war 6 Monate nach der Bolusgabe ein signifikantes Haarwachstum zu beobachten. Die Hälfte der Patienten mit multifokaler AA hatte nach 6 Monaten auf die Therapie angesprochen, aber weniger als ein Viertel der Patienten mit Alopecia totalis (AT) und Alopecia universalis (AU) waren Responder. Die Untersuchung der Langzeitergebnisse erfolgte nach durchschnittlich 12,3 Jahren; 8/10 der initialen Responder hatten eine leichte oder keine Erkrankung und 14/20 initialen Non-Responder litten an schwerer AA. Schlussfolgerungen: Diese Studie bestätigte die geringe kurz- und langfristige Wirksamkeit dieser Behandlung bei AT und AU.

Vergleichende Studie der systemischen Entzündungsreaktionen bei Psoriasis vulgaris und allergischer Kontaktdermatitis

Hintergrund: Psoriasis vulgaris (PV) ist mit einer niedriggradigen systemischen Entzündung verbunden. Ziel: Die Serummuster von Zytokinen und Wachstumsfaktoren wurden bei Patienten mit PV und allergischer Kontaktdermatitis (ACD) sowie bei gesunden Probanden untersucht, um systemische Entzündungsreaktionen bei diesen Erkrankungen zu beschreiben und zu vergleichen. Methoden: Insgesamt 12 entzündungssensitive Biomarker wurden mit Hilfe der Evidence Investigator™ Biochip-Technologie gleichzeitig analysiert. Ergebnisse: Bei PV waren der proinflammatorische Tumornekrosefaktor-α (TNF-α), Interferon-γ (IFN-γ), die Interleukine IL-1β, -2, -6, -8 und das Monozyten-Chemotaktische Protein-1 (MCP-1) erhöht. Bei ACD waren 2 Marker (TNF-α und MCP-1) erhöht und das regulatorische Zytokin IL-10 wies einen niedrigeren Wert auf. Das proinflammatorische IL-2 hatte bei PV und ACD die stärksten Korrelationen mit anderen pro- bzw. antiinflammatorischen Zytokinen, während IL-6 positiv mit dem Psoriasis Area and Severity Index korrelierte. Die Konzentrationen der Wachstumsfaktoren korrelierten mit MCP-1, jedoch nur bei PV. Schlussfolgerung: Obwohl PV eine vielfältigere proinflammatorische systemische Reaktion induziert, ist auch ACD mit einem systemischen Anstieg von Entzündungsmediatoren verbunden.