A Challenging Case of Metastatic Crohn's Disease Without Gastrointestinal Manifestations.

Metastatic Crohn's disease (MCD) is a rare cutaneous manifestation of Crohn's Disease (CD), defined as non-caseating, granulomatous skin lesions non-contiguous with the gastrointestinal (GI) tract. Most patients with MCD either have concomitant classic manifestations of CD or develop them within a few months to years. We report a case of MCD without known involvement of the GI tract, after more than three years from diagnosis. After failure or intolerance to several conventional treatments, including oral corticosteroids and azathioprine, adalimumab was initiated with a good response.  Diagnosis of cutaneous CD is made by a combination of clinical and histopathological findings. Therapeutic options include topical, intralesional, and systemic corticosteroids as well as topical and systemic immunosuppressants and immunomodulators. Surgical excision may be considered for refractory cases.

Case for diagnosis. A pruritic eruption of keratotic papules over the face and neck

Abstract Generalized eruptive keratoacanthoma of Grzybowski is a rare variant of multiple keratoacanthomas counting with about 40 cases reported. It is a chronic and progressive disease for which none of the described therapeutic options has been entirely satisfactory. We report a case of an 83-year-old female who presented with a 3-month history of extremely pruritic, multiple, skin-coloured to erythematous to brownish, millimetric papules, with a keratotic centre. Histological examination of an incisional biopsy was consistent with the diagnosis of keratoacanthoma. The patient started acitretin 25 milligrams daily with a complete resolution of pruritus and regression of numerous lesions.

Coats plus syndrome (cerebroretinal microangiopathy with calcifications and cysts-1): A case report.

We present a 6-year-old girl with skin hyperpigmentation, leukoplakia, and onychodystrophy, the classic mucocutaneous triad usually associated with dyskeratosis congenita. The patient also had premature graying of the hair, bone marrow failure, hepatitis, exudative retinopathy, osteopenia with multiple long bone fractures, and intracranial calcifications and brain cysts. Coats plus syndrome is a rare disease with a clinical and genetic overlap with dyskeratosis congenita. This disease is reviewed, with a focus on the pathogenesis of the genetic anomalies and its background as a telomere biology disorder.

Case for diagnosis. A pruritic eruption of keratotic papules over the face and neck.

Generalized eruptive keratoacanthoma of Grzybowski is a rare variant of multiple keratoacanthomas counting with about 40 cases reported. It is a chronic and progressive disease for which none of the described therapeutic options has been entirely satisfactory. We report a case of an 83-year-old female who presented with a 3-month history of extremely pruritic, multiple, skin-coloured to erythematous to brownish, millimetric papules, with a keratotic centre. Histological examination of an incisional biopsy was consistent with the diagnosis of keratoacanthoma. The patient started acitretin 25 milligrams daily with a complete resolution of pruritus and regression of numerous lesions.

Bilateral retinal detachment - when the kidney meets the eye / Descolamento de retina bilateral - quando o rim afeta o olho

ABSTRACT Exudative retinal detachment occurs when fluid accumulates between the neurosensory retina and the retinal pigment epithelium. Ocular diseases or multisystem conditions such as nephrotic syndrome may lead to exudative retinal detachment. This report describes a case of nephrotic syndrome secondary to minimal change disease, anasarca and bilateral serous macular detachment in an adult patient. A 75-year-old male patient presented to the emergency department with generalized edema, asthenia, and visual impairment. Medical history included a recent diagnosis of nephrotic syndrome secondary to minimal change disease, which had been controlled with corticosteroid therapy. At presentation, best corrected visual acuity was 20/100. Slit-lamp examination revealed xanthelasmas and mild bilateral eyelid edema and chemosis. Dilated fundus examination confirmed bilateral macular detachment. The patient did not respond to diuretic therapy. Ttherefore, hemodialysis was started. Two months later, visual acuity improved to 20/25 and near normal restoration of retinal anatomy was achieved, with concurrent remission of proteinuria. Exudative retinal detachment is a multifactorial condition. However, in diseases associated with severe hypoalbuminemia, such as nephrotic syndrome, low oncotic pressure in choroidal vessels and high interstitial pressure in the choroid may explain retinal detachment. Patients with chronic kidney disease carry a high risk of ophthalmic disease development. Several mechanisms that affect ocular vessels, the retina and the choroid are thought to be involved. A multidisciplinary approach is crucial to resolve the ophthalmic condition and improve overall health.

RESUMO O descolamento de retina exsudativo ocorre quando o fluido se acumula entre a retina neurossensorial e o epitélio pigmentado da retina. Patologias oculares isoladas ou doenças multissistêmicas, como a síndrome nefrótica, podem levar ao descolamento de retina exsudativo. Apresenta-se aqui o caso de um adulto com síndrome nefrótica por doença de lesões mínimas, anasarca e descolamento de retina exsudativo macular bilateral. Trata-se de um homem de 75 anos de idade, que recorreu ao serviço de urgência com edema generalizado, astenia e diminuição da acuidade visual. Os antecedentes pessoais incluíam diagnóstico recente de síndrome nefrótica secundária à doença de lesões mínimas, em uso de corticoterapia. Na apresentação, a melhor acuidade visual corrigida era 20/100. A biomicroscopia revelou xantelasmas, edema palpebral leve e quemose nos dois olhos. Fundoscopia mostrou descolamento macular bilateral. O doente iniciou diuréticos com pouca resposta clínica, tendo sido adicionada hemodiálise. Verificou-se melhora da acuidade visual para 20/25 e restauração quase total da anatomia da retina 2 meses após o início do tratamento, coincidindo com a remissão da proteinúria. A fisiopatologia dos descolamentos de retina exsudativos é multifatorial, mas, em doenças com hipoalbuminemia grave, como a síndrome nefrótica, a baixa pressão oncótica e a alta pressão intersticial na coroide podem explicar o descolamento macular exsudativo. Doentes com doença renal crônica constituem um grupo de risco para o desenvolvimento de doença ocular, envolvendo vários mecanismos que afetam vasos, retina e coroide. Uma abordagem multidisciplinar é crucial para a melhoria da doença oftalmológica e do estado geral do doente.

Tumoral melanosis after immunotherapy with pembrolizumab - a response sign mimicking melanoma.

Tumoral melanosis is a rare histopathological finding characterized by aggregates of melanophages, in the absence of melanocytes, usually observed in sites of regressed melanocytic lesions, including melanoma. A 72-year-old woman with a history of a completely excised melanoma on her right arm (T3bN0M0, Stage IIb) presented with clinically-evident regional lymph node metastasis. This was treated with right axillary lymphadenectomy. Subsequently, a 2-centimeter blue-colored patch over the excision scar was identified, along with a blue nodule within the posterior aspect of the same arm, consistent with in-transit metastases. Additional metastases on the right hilar region of the lungs were detected by PET/CT. Hence, the patient began immunotherapy with pembrolizumab. After three months, a second PET/CT revealed a complete response, but the patient maintained the blue-colored patch previously observed. Given the discrepancy between the clinical and metabolic response she underwent a skin biopsy; histological examination showed findings compatible with tumoral melanosis resulting from complete regression of a metastatic lesion. In cases of metastatic melanoma under immunotherapy with anti-PD1 agents, especially pembrolizumab, tumoral melanosis has been anecdotally associated with tumor regression and favorable treatment response. The patient has been maintained on pembrolizumab, accomplishing 15 cycles, and has had a complete response to date.

Complete Multilineage CD4 Expression Defect Associated With Warts Due to an Inherited Homozygous CD4 Gene Mutation.

Idiopathic T-CD4 lymphocytopenia (ICL) is a rare and heterogeneous syndrome characterized by opportunistic infections due to reduced CD4 T-lymphocytes (<300 cells/µl or <20% T-cells) in the absence of HIV infection and other primary causes of lymphopenia. Molecular testing of ICL has revealed defects in genes not specific to CD4 T-cells, with pleiotropic effects on other cell types. Here we report for the first time an absolute CD4 lymphocytopenia (<0.01 CD4+ T-cells/µl) due to an autosomal recessive CD4 gene mutation that completely abrogates CD4 protein expression on the surface membrane of T-cells, monocytes, and dendritic cells. A 45-year-old female born to consanguineous parents consulted because of exuberant, relapsing, and treatment-refractory warts on her hands and feet since the age of 10 years, in the absence of other recurrent infections or symptoms. Serological studies were negative for severe infections, including HIV 1/2, HTLV-1, and syphilis, but positive for CMV and EBV. Blood analysis showed the absence of CD4+ T-cells (<0.01%) with repeatedly increased counts of B-cells, naïve CD8+ T-lymphocytes, and particularly, CD4/CD8 double-negative (DN) TCRαß+ TCRγδ- T-cells (30% of T-cells; 400 cells/µl). Flow cytometric staining of CD4 using monoclonal antibodies directed against five different epitopes, located in two different domains of the protein, confirmed no cell surface membrane or intracytoplasmic expression of CD4 on T-cells, monocytes, and dendritic cells but normal soluble CD4 plasma levels. DN T-cells showed a phenotypic and functional profile similar to normal CD4+ T-cells as regards expression of maturation markers, T-helper and T-regulatory chemokine receptors, TCRvß repertoire, and in vitro cytokine production against polyclonal and antigen-specific stimuli. Sequencing of the CD4 gene revealed a homozygous (splicing) mutation affecting the last bp on intron 7-8, leading to deletion of the juxtamembrane and intracellular domains of the protein and complete abrogation of CD4 expression on the cell membrane. These findings support previous studies in CD4 KO mice suggesting that surrogate DN helper and regulatory T-cells capable of supporting antigen-specific immune responses are produced in the absence of CD4 signaling and point out the need for better understanding the role of CD4 on thymic selection and the immune response.

Demyelinating disease of the central nervous system associated with Pembrolizumab treatment for metastatic melanoma.

Immune checkpoint inhibitors are used in metastatic melanoma with good efficacy and safety profile. We report the first case of an inflammatory demyelinating disease of the central nervous system during treatment with Pembrolizumab and discuss the evidence in the literature supporting its causative role. The patient had a good clinical recovery after intravenous steroids, plasma exchange and discontinuation of Pembrolizumab. Due to the expected increase in the importance of immune checkpoint inhibitors in cancer treatment, it is important to be aware of neurological adverse events, as early treatment usually leads to good clinical responses.

Extraocular Muscles Involvement as the Initial Presentation in Metastatic Breast Cancer.

Orbital metastasis is a rare event, and metastatic disease affecting the extraocular muscles is an even less frequent complication of solid tumors. Herein, we report an unusual case of ptosis as the initial presentation of an invasive breast cancer. A 68-year-old woman presented with III and VI partial nerve paresis, secondary to a compressive retrobulbar mass. Magnetic resonance imaging revealed an infiltrative lesion involving the extraocular muscles. Tissue biopsy yielded a result compatible with metastasis to the orbit, with immunohistochemistry analysis suggesting breast as the primary organ. Mammography identified an area of architectural distortion; stereotactic wire-guided biopsy confirmed the result of the previous orbital biopsy. A positron emission tomography scan demonstrated disseminated disease. Palliative chemotherapy with bone-modulating agents and subsequent hormonal therapy was proposed. Unfortunately, the patient did not respond to therapy and died 38 months after diagnosis.

A challenged case of Vogt-Koyanagi-Harada syndrome: when dermatological manifestations came first.

INTRODUCTION: Vogt-Koyanagi-Harada syndrome (VKHS) is an inflammatory systemic autoimmune disease principally affecting pigmented tissues in the ocular, auditory, integumentary and central nervous systems. Patients are generally women in the fourth decade of life. The prognosis is correlated mainly with the time between diagnosis and the start of treatment and number of recurrent episodes of inflammation. Most complications are mainly ocular. The purpose of this paper is to describe a clinical case of VKHS. MATERIAL AND METHODS: A child with a challenging clinical presentation in which the dermatological symptoms occurred before ocular manifestations. DISCUSSION AND CONCLUSION: VKHS is rare in children and can be a diagnostic challenge. It seemed interesting to share this case as an opportunity to expand our knowledge of the clinical spectrum of diseases and reflect about current diagnostic criteria.

A Rare Case of Bilateral Proptosis.

A 65-year-old man presented with a 2-year history of severe bilateral proptosis, palpable lymphadenopathy and moderate hepatosplenomegaly. A blood test was positive for hepatitis C infection. CT showed palpebral infiltrative lesions with regional progression through the temporal and masticatory spaces to the pharynx and hypopharynx causing almost complete airway obstruction. A palpebral biopsy was consistent with low-grade Bcl-2+ extra-nodal MALT non-Hodgkin B-cell lymphoma. The patient received six cycles of rituximab-based chemotherapy with clinical remission at 9-month follow-up. Bilateral proptosis is a rare presentation of several diseases. When brain CT excludes cavernous sinus pathology, thyroid ophthalmopathy or haematological malignancy should be considered. LEARNING POINTS: Bilateral proptosis is a rare presentation with a broad differential diagnosis, and is most frequently is caused by cavernous sinus disease, thyroid ophthalmopathy or haematological malignancy.Hepatitis C may be associated with MALT lymphoma and presents mainly at non-gastric locations even with few hepatic manifestations of the infection.Long-term low-grade lymphoma may present with severe disseminated disease at diagnosis, but treatment response is generally good.

Erythema nodosum and sarcoid granulomas - letting the cat out of the bag.

A 41-year-old woman presented with a violaceous papule on the dorsum of the hand, large ipsilateral axillary lymphadenopathy, and tender, erythematous, subcutaneous nodules on the legs. Accompanying signs included fever, ankle swelling, and bilateral red eye. She recalled having a previous exposure to kittens one month before and had a positive family history for sarcoidosis. Histological examination of the hand lesion showed sarcoidal granulomas with positive Bartonella henselae DNA, whereas a biopsy done on the leg nodules was compatible with erythema nodosum. Cat scratch disease (CSD) typically presents as a tender regional lymphadenopathy preceded by an inoculation papule with spontaneous resolution occurring between 8-16 weeks. Cutaneous manifestations of CSD are rare, with erythema nodosum accompanying only 0.6% of cases. Although speculative, the background of a positive family history for sarcoidosis may explain the atypical presentation of this case, with red eye, persistent arthralgia, and associated sarcoidal granulomas.

Metastatic Crohn's disease despite infliximab therapy.

Metastatic Crohn's disease is a rare extraintestinal manifestation of Crohn's disease. It is characterized by polymorphic skin lesions formed by non-caseating granulomas located on anatomical sites distant from the gastrointestinal tract. We report a rare case of metastatic Crohn's disease, simultaneously displaying multiple clinically heterogeneous cutaneous lesions, in a patient with previously diagnosed Crohn's disease in remission due to anti-TNF-α use. This case highlights the need for high clinical suspicion and early biopsy in the setting of a patient with Crohn's disease and persistent skin lesions, even under biologic therapy. Furthermore, it reinforces the need of monitoring of the serum level of infliximab, increasing the dose in case it is low or undetectable.

[Choroidal Melanoma]. / Melanoma da Coroideia.

Choroidal melanoma is the most common primary intraocular malignant tumor in adults. None of the different treatments available offers advantages of survival, resorting more and more to conservative treatments such as brachytherapy, which has been available in Portugal since 2013. In this article we review the clinical characteristics, risk factors, diagnosis, complementary exams and therapeutic options in choroidal melanoma.

O melanoma da coroideia é o tumor primário intraocular maligno mais frequente em adultos. Nenhum dos diferentes tratamentos disponíveis oferece vantagens de sobrevida recorrendo-se, cada vez mais, a tratamentos conservadores como a braquiterapia, a qual passou a estar disponível em Portugal desde 2013. Neste artigo revemos as características clínicas, factores de risco, diagnóstico, exames complementares e opções terapêuticas no melanoma da coroideia.