Mar Llamas-Velasco

Biological Treatments in Atopic Dermatitis

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases that affect both children and adults with a prevalence of 30% and 10%, respectively. Even though most of patients respond satisfactory to topical anti-inflammatory drugs, about 10% require one or more systemic treatments to achieve good control of their illness. The progressive and increasingly detailed knowledge in the immunopathogenesis of AD has allowed research on new therapeutic targets with very promising results in the field of biological therapy. In this article, we will review the different biological treatments with a focus on novel drugs. Their mechanism of action, current status and results from clinical trials and observational studies will be specified.

Eccrine squamous syringometaplasia secondary to cutaneous extravasation of docetaxel: report of three cases

Eccrine squamous syringometaplasia is characterized by the metaplasia of cuboidal epithelial cells of the eccrine sweat ducts into squamous epithelial cells. It has been associated with several conditions including chemotherapy‐related bilateral dermatitis, an entity that can take place in body areas rich in eccrine glands, as well as in acral erythema related to chemotherapy. Only a few cases because of cutaneous extravasation of chemotherapy have been previously reported. We report three cases of eccrine squamous syringometaplasia secondary to extravasation of docetaxel.

Refractory generalized pustular psoriasis responsive to a combination of adalimumab and acitretin

combination of adalimumab and acitretin Editor, Generalized pustular psoriasis is a distinctive rare variant of psoriasis which may become complicated by systemic alterations. Its management causes some difficulties, despite the availability of new modes of treatment with biologic therapy. The combination of biologics with acitretin has already been described for the treatment of moderate-to-severe plaque psoriasis but not for pustular psoriasis. We report a patient with generalized pustular psoriasis resistant to systemic conventional and biologic therapy, treated successfully with adalimumab in combination with acitretin. A 21-year-old woman presented with a 14-year history of pustular eruptions arising on an erythematous skin associated with scaly erythematous plaques; this was diagnosed clinically and histologically as pustular psoriasis. The patient had suffered an icthyosiform dermatitis during early childhood but was otherwise healthy. She had initially been treated with topical agents and intermittent courses of oral acitretin (0.5–1.0 mg/kg/d) since October 1994. In January 2004, the patient developed an acute severe thrombocytopenia that led to acitretin interruption, although the causal relationship with the drug was unclear. The patient then experienced a flare in psoriasis accompanied by fever and general malaise. Over the following four years, she was treated with different drugs as monotherapy or in combination. Firstly, treatment with oral intermittent cycles of cyclosporin (3 mg/kg/d) was ineffective. Then, acitretin monotherapy was restarted (50 mg/d), but achieved only a partial improvement with no side effects. Psoralen combined with ultraviolet A (PUVA) therapy was administered with acitretin for 12 weeks for a total dose of 37.5 J/cm and achieved a partial response. During a second cycle of PUVA therapy, after two doses of 2.0 J/cm and 2.5 J/cm, the patient developed a severe generalized pustular flare of psoriasis and required hospitalization (Fig. 1). Oral methotrexate (20 mg/week) was started, but new episodes of malaise and disseminated cutaneous lesions proved this to be unsuccessful. Intravenous infusions of infliximab (6 mg/kg) were added to methotrexate. The patient presented an increase in transaminase levels, and methotrexate was substituted by acitretin. This combination facilitated a remarkable improvement in the patient’s psoriasis, achieving almost complete clearance of the lesions, but the effectiveness of the therapy decreased progressively and relapses occurred. Infliximab was then substituted by subcutaneous adalimumab (80 mg at baseline, 40 mg at week 1, and then 40 mg every two weeks), which, in combination with acitretin (50 mg/d), achieved a dramatic improvement in the skin lesions (Fig. 2). After 11 months of continuous treatment, the patient’s psoriasis remains well controlled despite the progressive reduction of the acitretin dose (to 30 mg/d). The combination of acitretin with a biologic agent represents, in some cases, a unique approach in the Figure 1 Severe pustular generalized flare requiring hospitalization

Primary cutaneous malignant granular cell tumor: an immunohistochemical study and review of the literature.

Granular cell tumors (GCTs) are uncommon soft tissue tumors characterized by cytoplasmic granular appearance of the neoplastic cells. Malignant granular cell tumors (MGCTs) comprise less than 2% of GCTs and are mostly found in the subcutaneous soft tissues of the lower extremities, especially the thighs. Very few cases have been reported in the skin. The uncommon occurrence of cutaneous MGCTs and their histopathologic similarities with their benign counterpart make difficult the diagnosis of this particular malignancy. We describe a primary cutaneous MGCT that presented as a left posterior chest wall mass in a 51-year-old woman. Local excision was performed for the primary tumor, which was first interpreted as an atypical GCT, but 3 months later a left axillary mass appeared, and subsequent axillary lymph node dissection demonstrated metastatic disease in 4 of 12 excised lymph nodes. We report the immunophenotype of this primary cutaneous MGCT, which was studied with an ample panel of antibodies and compare our results with those of the few previously reported cases in the skin and subcutaneous soft tissues.

Pharmacogenetics of ustekinumab in patients with moderate-to-severe plaque psoriasis

Aim/Materials & methods: Few studies have evaluated the influence of pharmacogenetics in psoriatic patients treated with ustekinumab. We evaluated 121 polymorphisms to study a possible association between these SNPs and the response to ustekinumab (PASI75 at 4 months; n = 69). RESULTS/CONCLUSION The adjusted results (false discovery rate) showed an association between five SNPs in TNFRSF1A, HTR2A, NFKBIA, ADAM33 and IL13 genes, and poor response to ustekinumab. Furthermore, six SNPs in CHUK, C17orf51, ZNF816A, STAT4, SLC22A4 and Corf72 genes were associated with better response to ustekinumab. However, there was no significant association between response to ustekinumab and SNPs in HLA-C as it has been recently described. Finally, a higher weight was obtained in nonresponders than responders (p = 0.018). Further studies would be necessary to be closer to personalized medicine.

Occlusive Nonvasculitic Vasculopathy.

Abstract: We review the most characteristic clinical and histopathologic findings of the cutaneous manifestations of the occlusive nonvasculitic vasculopathic disorders. Clinically, most of these conditions are characterized by retiform purpura. Histopathologic findings consist of occlusion of the vessel lumina with no vasculitis. Different disorders may produce nonvasculitic occlusive vasculopathy in cutaneous blood and lymphatic vessels, including embolization due to cholesterol and oxalate emboli, cutaneous intravascular metastasis from visceral malignancies, atrial myxomas, intravascular angiosarcoma, intralymphatic histiocytosis, intravascular lymphomas, endocarditis, crystal globulin vasculopathy, hypereosinophilic syndrome, and foreign material. Other times, the occlusive disorder is due to platelet pugging, including heparin necrosis, thrombocytosis secondary to myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, and thrombotic thrombocytopenic purpura. Occlusive vasculopathy may also appear in cold-related gelling agglutination, like that occurring in cryofibrinogenemia, cryoglobulinemia, cold agglutinin syndrome, and crystalglobulinemia. Microorganisms may also occlude the vessels lumina and this is especially frequent in ecthyma gangrenosum, opportunistic fungi as aspergillosis or fusariosis, Lucio phenomenon of lepromatous leprosy and disseminated strongyloidiasis. Systemic coagulopathies due to defects of C and S proteins, coumarin/warfarin-induced skin necrosis, disseminated intravascular coagulation, and antiphospholipid antibody/lupus anticoagulant syndrome may also result in occlusive nonvasculitic vasculopathy. Finally, vascular coagulopathies such as Sneddon syndrome, livedoid vasculopathy, and atrophic papulosis may also cause occlusion of the vessels of the dermis and/or subcutis. Histopathologic study of occlusive vasculopathic lesions is the first step to achieve an accurate diagnosis, and they should be correlated with clinical history, physical examination, and laboratory findings to reach a final diagnosis.

Polymorphisms associated with etanercept response in moderate-to-severe plaque psoriasis

AIM Few studies have evaluated the influence of pharmacogenetics in psoriatic patients treated with etanercept. MATERIALS & METHODS We evaluated the association between 124 polymorphisms with the response to etanercept in patients with moderate-to-severe plaque psoriasis at 3 months (n = 78) and 6 months of treatment (n = 68). RESULTS The results of the multivariate analysis showed an association between polymorphisms rs13437088 (HLA-B/MICA), rs96844 (MAP3K1), rs2431697 (PTTG1), rs9304742 (ZNF816A) and the response to etanercept at 3 months. Besides polymorphisms rs928655 (GBP6) and rs2546890 (IL12B) were associated to response at 6 months. CONCLUSIONS Nevertheless, these biomarkers should be validated in large-scale studies before its implementation in clinical practice.

Hypopigmented macules secondary to imatinib for the treatment of chronic myeloid leukemia: a histopathologic and immunohistochemical study

A few series addressing the cutaneous side effects related to imatinib in the skin have been published, but only one described scarce histopathologic information in seven patients.

Loss of Fumarate Hydratase and Aberrant Protein Succination Detected With S-(2-Succino)-Cysteine Staining to Identify Patients With Multiple Cutaneous and Uterine Leiomyomatosis and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.

Aims:Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance, and clinically challenging to diagnose. Immunohistochemical stainings may favor an earlier diagnosis. Methods and Results:The authors have tested 31 smooth muscle neoplasms. Ten of the 13 lesions from patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented strongly positive FH staining although 5 cases were negative. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. Anti-S-(2-succino)-cysteine (2SC) showed the opposite intensity staining pattern and showed great correlation with anti-FH (rho spearman = −0.797). Anti-2SC staining increased the diagnostic accuracy in 19% of the cases. Limitations:The main limitation of this study is the lack additional clinical data to further classify the cases as the case inclusion was histopathological. Conclusions:Negative FH staining could indicate a high risk of HLRCC but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. Thus, when there is a doubtful case, anti-2SC may be added to exclude the syndrome if a negative staining is found.

Cutaneous angiosarcoma mimicking xanthoma: a challenging histopathologic diagnosis with important consequences

Cutaneous angiosarcoma may show protean histopathologic features. Rare or uncommon variants include epithelioid, clear cell, granular cell, verrucous, pseudolymphomatous and signet‐ring cell types. Perhaps the rarest type consists of cutaneous angiosarcoma with xanthomization of neoplastic cells. We report an extraordinary case with almost all neoplastic cells exhibiting a xanthomatous appearance that was studied both histopathologically and immunohistochemically. We discuss the histopathologic differential diagnosis of foamy cell angiosarcoma with other neoplasms that may show similar histopathology.