TEMPI syndrome: A clinical, light-microscopic and phenotypic evaluation with review of the literature.

BACKGROUND AND OBJECTIVES: TEMPI (telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonaryshunting) syndrome is a rare multisystemic disease classified as a monoclonal gammopathy of cutaneous significance. The pathogenesis and etiology of TEMPIare not well known because of the rarity of this disorder. Although telangiectasias are the hallmark of this syndrome, skin biopsies are rarely performed. We aim to further characterize TEMPI syndrome through the evaluationof a skin biopsy. METHODS: We reviewed the histopathology and immunophenotypic profile of a skin biopsy from a 53-year-oldwoman diagnosed with TEMPI syndrome. Other components of her syndromic complex included an IgA myeloma, elevated vascular endothelial growth factor (VEGF), and erythrocytosis. RESULTS: A biopsy showed prominent vascular ectasia with some degree of microvascular basement membranezone thickening. Our patient had a reduction in neoplastic plasma cell burdenand clearing of her telangiectasias following myeloma directed treatment. CONCLUSIONS: TEMPI can beviewed as a reactive vascular paraneoplastic syndrome in the setting of a plasma cell dyscrasia. Elaboration of VEGF from neoplastic plasma cells is likely pathogenetically implicated and appears to be a common link that explains other vascular lesions associated with monoclonal gammopathy syndromes.

Cutaneous collagenous vasculopathy: A report of three cases.

Cutaneous collagenous vasculopathy is a rare pauci-inflammatory, superficial, cutaneous vasculopathy characterized by progressive fine-branching telangiectasias clinically, while light microscopically one observes dilated venules and capillaries within the superficial dermis exhibiting excessive Type IV collagen within the vessel wall. We present three cases of collagenous vasculopathy. Two cases were associated with certain autoimmune stigmata, including a positive serologic anti-endothelial cell antibody assay and positive lupus anticoagulant in one, while the third case had positive anti-ribonucleoprotein (RNP) antibodies. The latter case was associated with chronic hydroxyurea therapy for an underlying myeloproliferative disorder. We explore the role of immune- and non-immune-based endothelial cell injury in the pathogenesis of collagenous vasculopathy.

Post-COVID-19 vaccination IgA vasculitis in an adult.

Leukocytoclastic vasculitis has been reported in the setting of COVID-19 infection and post-COVID-19 vaccination. We report a case of IgA vasculitis (IgAV) post-COVID-19 vaccination, with immunoglobulin A (IgA) immune deposits in the skin and renal involvement. SARS-CoV spike protein immunohistochemical staining was negative. IgAV with skin and renal involvement is a potential reaction to COVID-19 vaccination.

The use of drug calendars for the diagnosis of cutaneous drug eruptions in the age of electronic medical records.

A morbilliform drug eruption is the most common condition leading to a dermatology consultation for a patient in the hospital. Timing is an important diagnostic tool since the onset of a skin rash usually takes place within days-to-weeks of the start of the implicated drug. A comprehensive, thorough, and reliable drug history by the clinician is essential. Therefore, to assist in the task of determining the causative medication of a new skin rash in a hospitalized patient, the creation of a drug calendar is recommended. The development of an electronic version of the drug calendar offers several benefits over the manual version. As the use of electronic medical records continues to become the standard in medicine, the electronic drug calendar will serve as an invaluable tool for the diagnosis of drug hypersensitivity.

Epidermotropic CXCR3 positive marginal zone lymphoma: a distinctive clinical histopathological entity potentially originating in the skin; it does not always indicate splenic marginal zone lymphoma.

Epidermotropic B cell lymphoma represents a rare form of marginal zone lymphoma presenting as a disseminated skin rash resembling pityriasis rosea. To date there are 8 reported cases. In addition to the widespread nature of the skin rash, there is a proclivity for spleen and bone marrow involvement raising consideration regarding its categorization as a systemic lymphoma. We present an 89-year-old man with epidermotropic B cell lymphoma, who presented with a pityriasis rosea-like skin rash. An initial diagnosis of diffuse large cell B cell lymphoma was made based on the extent of dermal-based large cell infiltration. However, after recognizing the epidermotropic component and the distinctive clinical presentation, a diagnosis of epidermotropic B cell lymphoma was rendered. There was minimal bone marrow involvement based only on flow cytometric analysis, but there was no apparent bone marrow or splenic involvement on routine light microscopic assessment. Remission was = achieved with single agent rituximab chemotherapy and the patient remained symptom free. The neoplastic CD20 positive epidermotropic B lymphocytes expressed CXCR3. Similar to the prior reported cases by the authors, the neoplastic cells expressed CXCR3, a chemokine whose organ and tissue specific ligands could contribute to its relatively indolent clinicalcourse.

Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.

Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous involvement of malignant pleural mesothelioma is a very rare entity, with only 11 cases reported in the literature. Here, we describe the case of a 75-year-old man with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous eruption 5 months after initial diagnosis, which revealed sarcomatoid features on skin biopsy. Histological analysis of malignancy progression through immunohistochemical staining of the pleural, lymph node, and skin tissue revealed gradual loss of calretinin and gain of desmin, supporting a transformation from epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported case of an epithelioid to sarcomatoid transformation of malignant pleural mesothelioma manifesting in a cutaneous presentation.

Resident Rounds Part III: Case Report: Fatal Cryptococcal Panniculitis in a Lung Transplant Recipient.

Cryptococcal panniculitis is a rare entity previously reported in only 13 solid organ transplant (SOT) recipients. Cutaneous cryptococcosis in SOT recipients warrants extensive systemic workup and treatment as if central nervous system (CNS) disease is present. It should be included in the differential diagnosis of panniculitis in the immunocompromised host, as early diagnosis and treatment are critical. We report a fatal case of cryptococcal panniculitis in a 44-year-old lung transplant recipient.

Persistent serpentine supravenous hyperpigmentation--a possible cutaneous manifestation of HIV infection or a normal racial variant: a report of 3 cases.

Persistent serpentine supravenous hyperpigmentation (PSSH) describes a hyperpigmentation of the skin overlying peripheral veins. This cutaneous finding is typically seen in association with systemic chemotherapy or collagen vascular diseases such as progressive systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Three dark-skinned patients with idiopathic serpentine supravenous hyperpigmentation (ISSH) without collagen vascular disease or prior intravenous cytotoxic treatments were reported. All 3 patients were dark-skinned men with symmetric, uniform hyperpigmentation of the supravenous network of the bilateral lower extremities that had been present for years. The serpentine supravenous hyperpigmentation on the lower extremities was uniform in width and color, which contrasts with the darker discoloration near the site of infusion seen with PSSH associated with chemotherapy. Interestingly, 2 of the patients had advanced human immunodeficiency virus (HIV) disease in association with their ISSH while the HIV status of the third patient was unknown. Thus, we contend that ISSH be considered a normal racial variant or a possible cutaneous manifestation of HIV disease.

Primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder: A clinical and histologic retrospective cohort study.

Clonally restricted, non-epidermotropic, low-grade, CD8-positive T-cell infiltrates of the skin was recognized as a unique form of indolent CD8-positive lymphoproliferative disease in 2007 when it was first called primary cutaneous indolent CD8-positive lymphoid proliferation. More recently, the designation of primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder has been used. It is unique as a cutaneous lymphoproliferative disorder because of relative uniformity in its clinical presentation and histomorphology. It has been recognized as having an interesting predilection for the ear and acral sites, characteristically presenting as a solitary lesion. The basic morphology is one characterized by a non-epidermotropic, tumefactive infiltrate of well-differentiated, noncerebriform, atypical, small- to intermediate-sized lymphocytes that exhibit a specific phenotype characterized by CD8 and TIA positivity in concert with a distinct perinuclear Golgi staining pattern for CD68. The typical presentation is in the context of a solitary lesion, which can be treated surgically or with local irradiation. We describe in detail two very unusual cases that expand the clinical spectrum of this condition given the non-acral localization, the multiplicity of lesions to involve the trunk and extremities, and, in one case, the stable but recalcitrant course over 30 years. In addition, the second patient developed paraneoplastic dermatomyositis. We also retrospectively review our database for other cases that represent the entity of primary cutaneous acral CD8-positive T-cell lymphoproliferative disorder and review the literature focusing on non-acral cases. Nomenclature evolution from its first recognition in 2007 to the present is discussed.

Cutaneous angiosarcoma with skin metastases and persistent bloody pleural effusions.

Cutaneous angiosarcoma is a rare aggressive malignancy of vascular origin that usually arises in the scalp or face of elderly men. We describe a case of primary cutaneous angiosarcoma with skin metastases and presumed metastases to the lung in a 58-year-old man who presented with persistent bloody pleural effusions, an asymptomatic nontraumatic red patch on the forehead of 2 to 3 months' duration, and a pair of purpuric papules on his left mid back of unknown duration. Cutaneous metastases of angiosarcoma are uncommon. Spontaneous persistent bloody effusions without hemoptysis are distinctly uncommon, and pleural fluid cytology is repeatedly negative in lung or pleural angiosarcoma, making it difficult to diagnose without tissue biopsy.

Human Polyomavirus 9-An Emerging Cutaneous and Pulmonary Pathogen in Solid Organ Transplant Recipients.

IMPORTANCE: We describe the first report to our knowledge of cutaneous and systemic pathogenicity of human polyomavirus 9 in solid organ transplant recipients. OBJECTIVE: Three solid organ transplant recipients developed a widespread, progressive, violaceous, and hyperkeratotic skin eruption. All died from pulmonary and multiorgan failure around 1 year from onset of the rash. Routine clinical diagnostic testing could not identify any causative agent; therefore, samples and autopsies were investigated for novel pathogens using high-throughput sequencing. DESIGN, SETTING, AND PARTICIPANTS: This case series, including 3 solid organ transplant recipients who developed characteristic pink, violaceous, or brown hyperkeratotic papules and plaques throughout the body, was conducted at the Columbia University Medical Center. Lesional skin biopsies were collected from all 3 patients and subjected to high-throughput illumina sequencing for identification of microbial pathogens. Human polyomavirus 9 was identified in lesional skin biopsies. We subsequently collected ocular swabs, oral swabs, urine samples, and blood samples from patients, and organ tissues at autopsy in 1 patient. We investigated these samples for the presence of human polyomavirus 9 using in situ hybridization and quantitative polymerase chain reaction (PCR) assays. MAIN OUTCOMES AND MEASURES: A description of the clinical and pathologic findings of 3 patients. RESULTS: This case series study found that human polyomavirus 9 was detected in the skin biopsies of all 3 patients by a capture-based high-throughput sequencing method platform (VirCapSeq-VERT). Human polyomavirus 9 was also detected in blood, oral, ocular swabs, and urine by real-time polymerase chain reaction (PCR) assay. In situ hybridization and quantitative PCR assays were performed on the skin biopsies from 3 patients and lung autopsy of 1 patient, which showed the presence of human polyomavirus 9 messenger RNA transcripts, indicating active viral replication and pathogenesis in the skin and lungs. CONCLUSIONS AND RELEVANCE: Human polyomavirus 9 was associated with the widespread cutaneous eruption. All 3 patients had progression of cutaneous disease, accompanied by clinical deterioration, pulmonary failure, and death. One patient underwent autopsy and human polyomavirus 9 was identified in the lungs and paratracheal soft tissue. These findings suggest that human polyomavirus 9 may be associated with cutaneous and possibly pulmonary infection and death in solid organ transplant recipients.

Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions.

Pralatrexate is a novel antifolate, which shows increased antitumor activity in human tumor xenograft studies in mice compared with methotrexate. We investigated the effects of pralatrexate in a patient with adult T-cell lymphoma/leukemia with significant skin involvement. Atypical lymphocytes in epidermal Pautrier microabscesses were positive for HTLV-1. After the patient presented with leukemic conversion and with worsening of an erythematous generalized papular rash, he received one dose of pralatrexate. Within one week, his skin developed innumerable small erosions limited to the areas of the papular rash, sparing unaffected skin. Here we present in vivo evidence that pralatrexate-induced erosions in skin affected by adult T-cell lymphoma/leukemia are a manifestation of apoptosis of tumor cells infiltrating the epidermis and are not the result of cytotoxicity by pralatrexate on keratinocytes. This distinction is critical and may profoundly influence the clinical decision to continue pralatrexate treatment. Pralatrexate-induced skin erosions may indicate response to treatment.

Lichen planus of the esophagus: what dermatologists need to know.

BACKGROUND: Esophageal lichen planus (ELP) is a rare manifestation of mucocutaneous lichen planus (LP). OBJECTIVES: We aimed to report our experience and review all cases of ELP reported in the English-language literature. METHODS: We report our experience with 4 cases and reviewed PubMed for reports of ELP. Cases were evaluated for age of onset, sex, location of LP, relationship of the onset of ELP to extra-ELP, endoscopic findings, whether biopsy was performed, histopathology of esophageal biopsy specimens, medical history (including gastrointestinal history), development of esophageal squamous cell carcinoma, therapies tried, and response to treatment. RESULTS: A total of 72 cases of ELP were studied. In all, 87% of patients were female, with a median age of 61.9 years at time of diagnosis. Dysphagia was present in 81% and odynophagia was present in 24%. Oral LP was present in 89%, anogenital/vulvar LP in 42%, and cutaneous LP in 38%. Fourteen patients developed ELP as the sole or first manifestation of LP. Proximal esophageal lesions were present in 64%, distal in 11%, and both proximal and distal in 26%. Histology was "consistent with" LP in 71%. Four patients developed squamous cell carcinoma in association with ELP. LIMITATIONS: This is a review of our cases and others reported in the literature. CONCLUSIONS: ELP is underrecognized and underreported. There is often a significant delay between the onset of symptoms and the diagnosis. Malignant transformation of ELP to squamous cell carcinoma has been reported.

Calcium may preferentially deposit in areas of elastic tissue damage.

BACKGROUND: Cutaneous calcification is an acquired disorder whereby insoluble, amorphous calcium salts deposit in the skin. Classically, cutaneous calcification is categorized as metastatic, dystrophic, idiopathic, or iatrogenic. OBJECTIVE: The purpose of this study was to further elucidate the underlying pathogenic mechanism for cutaneous calcification. METHODS: Three cases of cutaneous calcification, including clinical characteristics and associated histopathology, were reviewed. Previous reports of cutaneous calcification were searched for in the published literature and included. RESULTS: Calcium is distributed within areas of underlying tissue damage (ie, locus minoris resistentiae), and in our cases, occurred specifically at sites of chronic actinic damage and intravenous extravasation tissue injury. LIMITATIONS: A small number of clinical cases and previously published reports were reviewed. CONCLUSION: We hypothesize that cutaneous calcification may preferentially occur at anatomic sites where tissue integrity has been compromised (ie, locus minoris resistentiae). We suggest one potential mechanism: that cutaneous calcification occurs within dermis that contains damaged elastic fibers. Pseudoxanthoma elasticum may serve as a possible genetic disease model for this process.

Anti-laminin-332 mucous membrane pemphigoid associated with recurrent metastatic prostate carcinoma: hypothesis for a paraneoplastic phenomenon.

Anti-epiligrin cicatricial pemphigoid is an autoimmune blistering disorder that has recently been associated with the development of solid organ malignancy. We describe a patient with recurrent metastatic prostate carcinoma who was diagnosed with this disorder. We provide a hypothesis as to the relationship between the development of this disease and its possible association with cancer pathogenesis.

Drug hypersensitivity in the age of electronic medical records.

Cutaneous drug eruptions are a common adverse reaction to medication. Creation of a drug calendar that covers a two-week span prior to the onset of rash is useful to identify the culprit agent. However, the creation of a drug calendar is often labor intensive. We developed an electronic version of a drug calendar that has considerably increased the ease and efficiency of completing a dermatology consultation.

Pyoderma gangrenosum-like lesions in leukocyte adhesion deficiency I treated with intravenous immunoglobulin.

A 31-year-old Caucasian male with leukocyte adhesion deficiency I and a 20-year history of recurrent, painful cutaneous ulcerations on the extremities presented with fatigue and worsening pain in both legs. He had experienced minimal improvement in his leg ulcers from treatment with systemic steroids, numerous courses of systemic antibiotics, and brief trials of infliximab and mycophenolate mofetil. He was treated with monthly intravenous immunoglobulin infusions. Upon completion of six courses of intravenous immunoglobulin his ulcerations had nearly healed for the first time in a decade.

An unusual cutaneous manifestation of Crohn's disease.

A 61-year-old man with a 12-year history of quiescent Crohn's disease on mesalamine presented to his gastroenterologist in April 2009, complaining of abdominal cramping, diarrhea, and a 25-lb weight loss over 6 weeks. He did not respond to prednisone 50 mg and 6-mercaptopurine 100 mg daily. Abdominal computed tomography findings revealed diffuse submucosal edema consistent with extensive colitis. Colonoscopy demonstrated diffuse inflammation with erythema, friability, and shallow ulcerations in the rectum and colon. Biopsies were consistent with Crohn's colitis. He was admitted for infliximab infusion for his unremitting diarrhea. Five days before admission, the patient noted mild swelling and redness of the left lower eyelid, which progressed to involve the right lower eyelid with frank pus draining from both eyes. He had no visual impairment or eye pain. Two days before admission, an ophthalmologist prescribed a steroid eyedrop with no relief. He also complained of seropurulent painful skin lesions on his face and scalp, which spread to involve his upper trunk and proximal arms. On admission to the hospital, dermatology, ophthalmology, and infectious disease consultations were obtained to rule out disseminated infection before initiation of infliximab therapy. The patient was afebrile and hemodynamically stable. His oral mucosa was normal. He had prominent bilateral lower eyelid edema, erythema, and superficial erosions with hemorrhagic crusting and frank green purulent drainage from both eyes, with crusting along the lower lash line and bilateral sclera injection (Figure 1). On his scalp, face, trunk, and proximal extremities, he had 25 to 30 erythematous, 4- to 8-mm papulopustules with narrow red halos, some with central necrosis and crusting (Figure 2). Cultures from the purulent ocular drainage and pustules on the trunk and arms were all negative for bacteria, virus, and fungi. Gram stain from the eye drainage showed polymorphonuclear leukocytes without organisms. Tissue cultures were negative for bacterial, fungal, and mycobacterial infection. Skin biopsy taken from the central upper back demonstrated subcorneal pustules with areas of eroded epidermis and collections of neutrophils in the superficial dermis (Figure 3). Special stains were negative for organisms. He received infliximab infusion 5 mg/kg for a total dose of 420 mg over 2 hours. Within 48 hours of infusion, there was notable decrease in size of lesions, in addition to reduction of purulent drainage from both eyes. The patient was discharged home following infliximab infusion. His skin lesions resolved during a period of 2 weeks, leaving small pink atrophic scars. He received his second infusion of infliximab 2 weeks after discharge with continued improvement in his gastrointestinal symptoms.

Cutaneous manifestations of Strongyloides stercoralis hyperinfection in an HIV-seropositive patient.

A 41-year-old human immunodeficiency virus (HIV)-positive man was hospitalized with complaints of a 4-week history of nausea and vomiting, associated with decreased oral intake, and a 4-day history of frontal headache and fever. His medical history was significant for a gunshot wound to the head 3 years prior, with a residual seizure disorder. He also had two previous hospitalizations, both for culture-negative bacterial meningitis; the first episode occurred 12 months before admission and the second episode occurred 5 months later. At that time, he was found to be positive for serum antibodies against HIV and a CD4+ T-lymphocyte count of 126/mm3. He had no known drug allergies and was not receiving any medication. On admission, the patient was febrile (104.0 degrees F) and hypotensive (blood pressure, 92/40 mm Hg). Pertinent physical examination findings included cachexia with bitemporal wasting, dry mucus membranes, adherent white patches on the oral mucosa, and negative Kernig's and Brudzinski's signs. His laboratory results revealed macrocytic anemia, a decreased serum sodium of 125 mEq/L, and a normal total leukocyte count with a CD4+ T-lymphocyte count < 50/mm3. Lumbar puncture opening pressure was elevated at 160 mm Hg, and cerebrospinal fluid analysis showed an increased white cell count of 97/microL (84% lymphocytes), a decreased glucose level of 26 mg/dL, and a decreased protein level of 42 mg/dL. The patient was started on empiric therapy that included intravenous ampicillin and cefotaxime, oral Bactrim, and clotrimazole lozenges for thrush. Cerebrospinal fluid culture was positive for Escherichia coli, sensitive to cefotaxime. Two days later, the patient developed fine, erythematous, nonblanchable macules primarily on his abdomen, with minimal involvement of his thorax and back. His skin lesions remained unchanged for the next 2 weeks. Repeat lumbar puncture was performed after 14 days of cefotaxime. The cerebrospinal fluid analysis showed an elevated white cell count of 7/microL (100% lymphocytes), a decreased glucose level of 53 mg/dL, and a decreased protein level of 33 mg/dL. The cerebrospinal fluid culture was now positive for Pseudomonas aeruginosa resistant to cefotaxime. The patient was started on imipenem. On day 34 of his admission, the patient became tachypneic with complaints of dyspnea. A chest roentgenogram revealed bilateral patchy infiltrates. He was transferred to the intensive care unit and intubated for hypoxemic respiratory failure (arterial blood gas values on 6 L of oxygen: pH, 7.46; bicarbonate, 23; and oxygen saturation, 37). That evening, the patient was also noted to have diffuse petechiae and purpura in a reticulated pattern over his abdomen (Figure 1A and 1B), most heavily concentrated in the periumbilical region, extending to the axillae and upper thighs. A 3x3-mm punch biopsy from abdominal skin demonstrated Strongyloides stercoralis larvae in the dermis (Figure 2A and 2B). His sputum specimen was teeming with adult S stercoralis worms (Figure 3) and, subsequently, numerous S stercoralis larvae were observed not only from the bronchoalveolar lavage but also from the nasogastric fluid specimen. These findings confirmed the diagnosis of disseminated strongyloidiasis. On hospital day 35, the patient was doing poorly and was started on thiabendazole (1250 mg twice daily for 28 days). Nine days later, ivermectin (4.5 mg once daily for 3 days for 2 courses) was also added. He continued to clinically deteriorate. The patient died 31 days after systemic antihelminthic treatment was initiated.

Contemporary applications and limitations of magnetic resonance imaging contrast materials.

PURPOSE: Improvements in imaging technologies have dramatically increased the ability to accurately diagnose and treat many urological disease processes. As urological patients often have chronic kidney disease, the well characterized nephrotoxicity of contrast induced nephropathy when using iodine based contrast materials has long been a concern. With the development of gadolinium based contrast agents it seemed that the concern regarding nephrotoxicity had been resolved. In 1997 a new disorder, nephrogenic systemic fibrosis, appeared in patients with severe renal failure. Nephrogenic systemic fibrosis is a serious and potentially devastating disorder characterized by progressive thickening and hardening of the skin and other body tissues, and complicated by flexion contractures of the joints. MATERIALS AND METHODS: We performed a survey of the available literature on nephrogenic systemic fibrosis and magnetic resonance contrast media. We focused on mechanisms in the development of nephrogenic systemic fibrosis as well as its association with magnetic resonance contrast media, disease treatment and prevention, and its relevance to clinical urology. RESULTS: An association between nephrogenic systemic fibrosis and gadolinium based contrast agents has been reported. Gadolinium is a toxic metal and it must be chelated to be a safe injectable contrast agent. It is now hypothesized that the majority of nephrogenic systemic fibrosis cases present with gadolinium based contrast agent exposure as the triggering factor, although this mechanism has not been elucidated. As gadolinium enhanced magnetic resonance imaging is an important tool in the diagnosis and surveillance of urological diseases, the severe consequences of nephrogenic systemic fibrosis demand that practicing urologists understand and know its history and treatment strategies. CONCLUSIONS: This review provides clarification of the gadolinium based contrast agent characteristics, tissue interactions that lead to the development of nephrogenic systemic fibrosis, prevention possibilities and available treatment options.