Association between alopecia areata, psoriasis vulgaris, thyroid disease, and metabolic syndrome.

Although the association between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both women ultimately progressed to treatment-resistant alopecia universalis. This constellation of autoimmunity and metabolic syndrome presents a therapeutic challenge while highlighting the need for full laboratory assessment of AA patients. Careful selection of biological treatment regimens may offer therapeutic benefit for both their psoriasis and AA while giving us experience with the newer biologics in AA.

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.

Pyoderma gangrenosum, acne and suppurative hidradenitis syndrome following bowel bypass surgery.

The clinical triad of pyoderma gangrenosum (PG), acne and suppurative hidradenitis (PASH) has recently been described as a new disease entity within the spectrum of autoinflammatory syndromes, which are an emerging group of inflammatory diseases distinct from autoimmune, allergic and infectious disorders. PASH syndrome is similar to PAPA (pyogenic arthritis, acne and PG), but it differs in lacking the associated arthritis and on a genetic basis. PAPA syndrome is caused by mutations in a gene involved in the regulation of innate immune responses, the PSTPIP1, while no mutations have been detected to date in patients with PASH syndrome. We report a young male patient who developed coexisting disseminated PG, typical suppurative hidradenitis and acneiform eruption on the face, after he had undergone bowel bypass surgery for obesity. The cutaneous manifestations associated with bowel bypass syndrome often mimic PG or other neutrophilic dermatoses, suggesting a pathogenesis related to neutrophil-mediated inflammation for this condition. This is the first report describing PASH syndrome after bariatric surgery, and we propose to include such neutrophilic dermatoses in the list of complications occurring after bowel bypass surgery. Extensive genetic studies may help to clarify the etiopathogenesis of PASH as well as of autoinflammatory diseases in general.

Livedoid vasculopathy in a patient with lupus anticoagulant and MTHFR mutation: treatment with low-molecular-weight heparin.

Livedoid vasculopathy is characterized by painful purpuric lesions on the extremities which frequently ulcerate and heal with atrophic scarring. For many years, livedoid vasculopathy has been considered to be a primary vasculitic process. However, there has been evidence considering livedoid vasculopathy as an occlusive vasculopathy due to a hypercoagulable state. We present the case of livedoid vasculopathy in a 21-year-old female who had been suffering of painful lower extremity lesions of 3 years duration. The patient was found to be lupus anticoagulant positive and homozygous for methylenetetrahydrofolate reductase C677T mutation. The patient was successfully treated with low-molecular-weight heparin.

Cutaneous manifestations of anti-angiogenic therapy in oncology: Review with focus on VEGF inhibitors.

The role of the VEGF signaling pathway in angiogenesis has been extensively investigated, and many new targeted anti-angiogenic drugs have evolved from this knowledge. The recent approval and introduction of these anti-neoplastic drugs has revolutionized the treatment of many types of cancers, but has also revealed numerous toxicities to the skin and its adnexae. Since these cutaneous side effects may have a significant impact on the physical, emotional and psychosocial health of patients, it is important for dermatologists and oncologists alike to be aware of the cutaneous complications of these drugs in order to properly diagnose and treat them. This review will detail the presentation of the cutaneous complications of the anti-angiogenic drugs, most notably bevacizumab, sorafenib and sunitinib, and shed light on the management of such adverse reactions.

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.

Autoinflammatory skin disorders in inflammatory bowel diseases, pyoderma gangrenosum and Sweet's syndrome: a comprehensive review and disease classification criteria.

Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) are skin diseases usually presenting with recurrent ulcers and erythematous plaques, respectively. The accumulation of neutrophils in the skin, characteristic of these conditions, led to coin the term of neutrophilic dermatoses to define them. Recently, neutrophilic dermatoses have been included in the group of autoinflammatory diseases, which classically comprises genetically determined forms due to mutations of genes regulating the innate immune response. Both PG and SS are frequently associated with inflammatory bowel diseases (IBDs); however, IBD patients develop PG in 1-3 % of cases, whereas SS is rarer. Clinically, PG presents with deep erythematous-to-violaceous painful ulcers with well-defined borders; bullous, pustular, and vegetative variants can also occur. SS is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions, and a diffuse neutrophilic dermal infiltrate. It is also known as acute febrile neutrophilic dermatosis. Treatment of PG involves a combination of wound care, topical medications, antibiotics for secondary infections, and treatment of the underlying IBD. Topical therapies include corticosteroids and the calcineurin inhibitor tacrolimus. The most frequently used systemic medications are corticosteroids and cyclosporine, in monotherapy or in combination. Dapsone, azathioprine, cyclophosphamide, methotrexate, intravenous immunoglobulins, mycophenolate mofetil, and plasmapheresis are considered second-line agents. Hyperbaric oxygen, as supportive therapy, can be added. Anti-TNF-α agents such as etanercept, infliximab, and adalimumab are used in refractory cases. SS is usually responsive to oral corticosteroids, and the above-mentioned immunosuppressants should be considered in resistant or highly relapsing cases.

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.

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.

Renal venous thrombosis in a newborn with prothrombotic risk factors.

Renal venous thrombosis (RVT) is a rare but a well recognized entity in children and neonates. The clinical signs of neonatal RVT include hypertension, enlarged kidney(s), hematuria, renal insufficiency, proteinuria, thrombocytopenia, or all. Persisting impairment of kidney function and hypertension are serious and common complications in patients with RVT. Risk factors for the development of RVT include maternal diabetes mellitus, pathologic states associated with thrombosis (e.g., shock, dehydration, perinatal asphyxia, polycythemia), and sepsis. Inherited prothrombotic abnormalities have been described in some reports of RVT. We report the case of a male newborn with left RVT and associated homozygosity for both factor V Leiden (G1691A) and methylenetetrahydrofolate reductase C677T mutations in addition to elevated serum lipoprotein (a). The patient was treated with heparin. We believe our case to be the first reported case in the English medical literature of such an association between neonatal RVT and homozygosity for both factor V Leiden and methylenetetrahydrofolate reductase. This case and other studies clearly demonstrate that neonatal RVT should be evaluated for thrombophilia conditions.