Erythematous Maculopapular Rash Research Articles

Abstract LB-136: IL-21-derived melanoma-reactive CTL combined with anti-CTLA4 persist, acquire central memory characteristics, and mediate tumor regression in patients with metastatic melanoma

Abstract Adoptive transfer of melanoma-reactive CD8+ T Cells (CTL) has demonstrated antitumor activity that may be enhanced by prolonging survival of transferred T cells in vivo. CTLA4 is up-regulated on activated T cells and when engaged to its B7-ligand, delivers inhibitory signals that impede TCR signaling, IL-2 transcription, and T cell proliferation. Human anti-CTLA4 monotherapy benefits about 25% of patients (pts), but most pts likely lack a sufficiently high frequency of pre-existing melanoma-reactive T cells susceptible to CTLA4 blockade and fail to respond. We propose a combined biologic strategy involving the adoptive transfer of melanoma-reactive CTL with concurrent administration of anti-CTLA4 as a means of enhancing the in vivo CTL survival and anti-tumor effect. Autologous polyclonal CTL were generated by multimer sorting and expanding melanoma-specific CTL lines to increase the probability of infusing cells derived from central memory (Tcm), as such cells were shown to exhibit prolonged persistence and superior replicative potential in murine and non-human primate models. Ex-vivo cultures were supplemented with the γc-chain cytokine Interleukin-21 (IL-21), which has been demonstrated to promote effector CTL helper-independence and to arrest differentiation at a Tcm stage. To date, 6 pts with bulky, therapy-resistant progressive melanoma were infused with 1010/m2 polyclonal IL-21-derived CTL targeting MART1. The infusions were preceded by intravenous cyclophosphamide 300mg/m2 and followed by low-dose subcutaneous IL-2 (250,000 IU/m2 BID) x 14 days. Anti CTLA4 (ipilimumab) 3mg/kg was started on the day after the CTL infusion. Side effects included fevers and chills starting 1-2 hours post-CTL infusion and moderately erythematous maculo-papular skin rashes in all 6 patients. No unexpected or serious (grade ≥3) toxicity was observed. Persistence of the infused CTL to frequencies >2x baseline levels was documented at 6 weeks (5/5 evaluable pts) and 12 weeks (4/4 pts). 3/5 and 2/3 evaluable pts experienced stable disease by RECIST 1.1 criteria at 6 and 12 weeks respectively. One patient had a delayed response with 25% reduction in tumor mass at 12 weeks after having failed previous ipilimumab monotherapy and prior CTL therapy without CTLA4 blockade. Tracking of infused multimer+ CTL in vivo revealed acquisition of both phenotypic (CD27, CD28, CD127, CD62L and CCR7) and functional (secretion of IL-2 in response to cognate antigen) characteristics of Tcm within 12 weeks. Our preliminary results suggest polyclonal IL-21-stimulated CTL targeting melanoma in combination with Ipilmumab is safe and promotes persistent anti-tumor responses such that CTL are poised for enhanced therapeutic activity in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-136. doi:1538-7445.AM2012-LB-136

Patient With a Rash, Abdominal Pain, and Weight Loss

A 49-YEAR-OLD MAN PRESENTS WITH RIGHT ILIAC FOSSA PAIN OF 36 HOURS’ duration. He reports loss of appetite, weight loss, and increasing lethargy over the preceding 10 months with intermittent constipation but no other symptoms. He describes asymmetric altered sensation in his distal lower limbs with left worse than right. The patient smokes, has a history of illicit amphetamine and cannabinoid use, and acquired tattoos in a correctional facility. Past medical history is remarkable for an idiopathic splenic infarction 6 months ago. On physical examination, he is cachectic and he has right iliac fossa tenderness and percussion tenderness. He has a demarcated, erythematous maculopapular rash across his torso and limbs (FIGURE 1). Neurological examination reveals an asymmetric lower limb sensory neuropathy. Laboratory findings include leukocytosis (whitebloodcells, 16 900/μL), elevated inflammatorymarkers (C-reactiveprotein,109g/L; erythrocyte sedimentationrate, 27 mm/h), elevated rheumatoid factor (269 IU/L), low C3 and C4 (0.24 and 0.05 g/L, respectively), and a low titer of atypical perinuclear antineutrophil cytoplasmic antibody(ANCA),not selective foreitherproteinase3ormyeloperoxidase.Doublestranded DNA and extractable nuclear antibodies are negative. Cryoglobulins and serology for human immunodeficiency virus, hepatitis B, and hepatitis C are negative. Renal function is normal with normal urinary sediment. Abdominal computed tomographyrevealsmild thickeningof theascendingcolonandthepreviouslydocumented splenic infarction (FIGURE 2). What Would You Do Next?

Overview of T-cell depletion in haploidentical stem cell transplantation.

Overview of T-cell depletion in haploidentical stem cell transplantation.

Trichloroethylene Hypersensitivity Syndrome: A Disease of Fatal Outcome

Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.

Successful Tolerance of Deferasirox Following Desensitization for Significant Skin Rash

Abstract 5280 BACKGROUND:Deferasirox is an oral iron chelator that has become available in recent years. The long term tolerability profile of deferasirox is still being evaluated, however a common side effect is skin rash, which may occur in up to 10% of patients. This is usually mild to moderate and resolves with continued treatment. More severe rash may require interruption of therapy and reintroduction of deferasirox at a lower dose followed by gradual dose escalation. A short course of corticosteroids may be used. Occasional cases of angioedema have been reported for which cessation of deferasirox is recommended but re-introduction is difficult. We report three patients with hypersensitivity to deferasirox, two manifested as NCI CTC grade 3-skin rash and one as grade 1-skin rash. All were able to tolerate deferasirox following desensitization. METHODS:Two patients with β thalassaemia major and one with congenital sideroblastic anemia, all with transfusional iron overload, experienced skin rash to deferasirox and received a desensitization protocol, given orally as follows:Solution 1 (deferasirox 1.25 mg/ml):1 ml given days 1–32 ml given days 4–65 ml given days 7–9Followed by Solution 2 (deferasirox 12.5 mg/ml)1 ml given days 10–122 ml given days 13–155 ml given days 16–18The dose of deferasirox was subsequently increased by 125 mg/day every week until the desired dose was reached.RESULTS: Case 1:A 23 year-old female with b thalassaemia major, non-compliant with deferoxamine, was switched to deferasirox 1500 mg/day (20mg/kg/day). Nine days after starting deferasirox she experienced a low grade fever, extensive erythematous maculopapular rash and facial edema. Deferasirox was discontinued. Two days later the rash had progressed; prednisone was started at 50 mg/day and the rash resolved within 1 week. While still tapering prednisone (20 mg/day), deferasirox was re-started at 500 mg/day. The rash recurred within 2 days and deferasirox was discontinued. One year later the desensitization protocol was given and well tolerated without the development of skin rash; she is currently receiving deferasirox 1500 mg/day without difficulty. Case 2:A 21 year-old female with b thalassaemia major, non-compliant with deferoxamine, was switched to deferasirox 1500mg/day (20mg/kg/day). Ten days after starting deferasirox she developed diffuse erythema multiforme. Deferasirox was stopped and prednisone started at 1mg/kg/day with marked improvement. Five days later, still on prednisone in full doses, she was re-challenged with deferasirox 500 mg/day. The rash recurred and deferasirox was discontinued. One year later, the desensitization protocol was given and well tolerated without the development of skin rash. She is currently receiving deferasirox 1500mg/day without difficulty. Case 3:A 23 year-old female with congenital sideroblastic anemia receiving deferoxamine was switched to deferasirox 1500mg/day (20mg/kg/day) for ease of administration. Eight days after starting deferasirox she developed a maculopapular rash confined to the palms of the hands and soles of the feet, but associated with severe pruritis. Deferasirox was stopped and the patient declined prednisone. She resumed deferoxamine and was offered the deferasirox desensitization protocol. Desensitization was given successfully but required a three day extension of treatment with solution 1 (2ml) because of recurrent rash, which resolved over the following two days with the temporary addition of benadryl. She is currently receiving deferasirox 150mg/day on weekly dose escalation without difficulty. CONCLUSION:Deferasirox is often the chelation agent preferred by patients given its ease of administration. Given its documented reduction in total body iron, with promising effects on the removal of myocardial iron, the use of this agent is increasing. However, skin rash is a side effect that may limit the use of deferasirox in some patients. To our knowledge, this is the first report of a protocol that may successfully desensitize patients with hypersensitivity reactions to deferasirox, allowing them to tolerate this agent in therapeutic doses. Disclosures:Leitch:Novartis Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus in a young woman after ear piercing: a case report

IntroductionEar piercing is a common practice among Korean adolescents and young women and usually is performed by nonmedical personnel, sometimes under suboptimal hygienic conditions. Consequently, ear piercing has been associated with various infectious complications, including fatal infective endocarditis. We report a case of infective endocarditis that was caused by community-associated methicillin-resistant Staphylococcus aureus after ear piercing and that was accompanied by a noticeable facial rash.Case presentationA 29-year-old Korean woman underwent ear piercing six days before hospitalization. On admission, she had fever, erythematous maculopapular rashes on her face, signs of generalized emboli, vegetation in her mitral valve, and methicillin-resistant S. aureus bacteremia. On the basis of the blood culture results, she was treated with vancomycin in combination with gentamicin. On day six of hospitalization, a rupture of the papillary muscle of her mitral valve developed, and emergency cardiac surgery replacing her mitral valve with a prosthetic valve was performed. After eight weeks of antibiotic therapy, she was treated successfully and discharged without significant sequelae.ConclusionsNumerable cases of body piercing-related infective endocarditis have been reported, and since ear piercing is commonplace nowadays, the importance of risk recognition cannot be overemphasized. In our report, a patient developed infective endocarditis that was caused by methicillin-resistant S. aureus after ear piercing and that was accompanied by an interesting feature, namely facial rash.

CRESCENTIC GLOMERULONEPHRITIS AND LEUCOCYTOCLASTIC VASCULITIS ASSOCIATED WITH ACUTE EBV INFECTION

We report a case of leucocytoclastic vasculitis with crescentic glomerulonephritis in association with acute EBV infection. nep_1440 617..618 A 14 year old male presented to us with history of sudden onset of fever and skin rashes initially over the trunk and gradually involving the entire body including the face for 10 days. He was febrile and breathless with a blood pressure of 110/60 mmHg. He had conjunctival suffusion with a diffuse erythematous maculopapular rash. Systemic examination revealed hepatosplenomegaly with pulmonary congestion. His laboratory investigations revealed thrombocytopenia (87000/cmm) with acute renal failure (creatinine 1.7 mg/dL). Urinalysis showed 2+ proteinuria, haematuria and red blood cell casts with spot urine protein to creatinine ratio of 1.74. His blood and urine culture was negative and 2-D echocardiography was normal. Serum complement 3 and 4 levels were low and vasculitis work-up was negative. Serum for EBV capsid antigen (VCA) was highly positive with increasing titres. He had normal bone marrow studies and skin biopsy suggestive of leucocytoclastic vasculitis. He was treated with i.v. ceftriaxone and other supportive measures but he continued to have high grade fever with worsening azotemia (creatinine 5.2 mg/dL). Percutaneous kidney biopsy revealed severe proliferative glomerulonephritis with cellular crescents in more than 50% of the glomeruli (Fig. 1). He was treated with i.v. methyl prednisolone 500 mg once daily on 3 consecutive days followed by 1 mg/kg day p.o. Following this, his respiratory symptoms subsided, rashes started fading and his urine output improved. His serum creatinine dropped to 0.8 mg/dL with disappearance of proteinuria and haematuria. The finding of leucocytoclastic vasculitis on skin biopsy is suggestive of small-vessel vasculitis. The possible pathophysiological mechanism is either direct invasion of endothelial cells by EBV or by immune complex-mediated inflammation. Renal involvement in EBV infection is predominantly interstitial, 2 overt renal failure is uncommon 3 and crescentic glomerulonephritis has never been reported. Crescentic glomerulonephritis and small-vessel vasculitis in the presence of Ig M VCA antibodies in our patient may have resulted from an intense immune response to the EBV infection. Simultaneous decrease in C3 and C4 indicating classical complement activation along with prompt response to immunosuppressive therapy supports this possibility. Thus, we hypothesize that EBV infection should be included in the differential diagnosis while treating a patient with crescentic glomerulonephritis.

Case 1: Persistent fever in a toddler

A previously well 20-month-old girl, with a two-week history of persistent fever and neutropenia, was transferred from a secondary care hospital for investigation to rule out a possible diagnosis of leukemia. There was no history of infectious contacts or viral prodrome. The patient previously visited the family physician and emergency room on days 3, 7 and 12 of the fever, and was diagnosed with acute otitis media. She was treated with clarithromycin until day 7, when she was switched to amoxicillin due to continued fever. The medical history revealed a fully immunized, healthy child of Asian descent who, at nine months of age, developed a maculopapular rash following seven days of treatment with amoxicillin and ibuprofen for acute otitis media. A physical examination revealed an irritable child with a fever of 40°C, a new-onset generalized erythematous maculopapular rash and a palpable spleen, but no lymphadenopathy. The remainder of the examination was unremarkable. Specifically, there were no findings of nonpurulent conjunctivitis, oral-mucosal changes, cervical lymphadenopathy, palmar or plantar changes, cardiac murmur or arthritis. The initial workup revealed pancytopenia (absolute neutrophil count 0.2×109/L, hemoglobin 70 g/L, platelets 119×109/L), hypoalbuminemia, an elevated erythrocyte sedimentation rate (ESR), an elevated C-reactive protein (CRP) level, a positive Epstein-Barr virus (EBV) polymerase chain reaction (12,100 copies detected) and splenomegaly on abdominal ultrasound. Bone marrow biopsy and hemoglobin electrophoresis findings were normal. Other negative test results for infections included urine, blood and stool cultures, and serology for cytomegalovirus, varicella, hepatitis A, B and C, and HIV I and II. Because of a possible penicillin allergy, she was empirically treated with vancomycin and meropenem, which were discontinued following negative blood and urine cultures. She was also transfused with packed red blood cells and albumin because of low hemoglobin and albumin levels. The patient improved clinically and was discharged on day 21 of fever onset. She was febrile but clinically stable. The diagnosis was believed to be EBV infection and a subsequent hypersensitivity vasculitis reaction to penicillin. The toddler initially improved, then worsened with new-onset jaundice, irritability and hepatomegaly. She returned five days later with the following laboratory findings: pancytopenia (absolute neutrophil count 0.4×109/L, hemoglobin 76 g/L, platelets 24×109/L), hypertriglyceridemia (12.4 mmol/L), hypofibrinogenemia (1.56 g/L), hyperferritinemia (1230 μg/L), hyperbilirubinemia (68.7 μmol/L), transaminitis (alanine aminotransferase 313 U/L, aspartate aminotransferase 1507 U/L), coagulopathy (international normalized ratio 1.2, partial thromboplastin time 67 s) and a lactate dehydrogenase level of 5364 U/L. Her CRP level increased from 42 mg/L to 56 mg/L but her ESR decreased from 62 mm/h to 16 mm/h. A diagnosis was made based on the clinical findings and laboratory test results.

Erythematous Maculopapular Rash Covering Entire Body

Erythematous maculopapular rash covering entire body.Physical examination shows an erythematous maculopapular rash covering the infant’s entire body, including the face, trunk, and extremities, but no rash on the palms and soles. Lesions are in various stages of healing, with some appearing vesicular. Mucous membranes are spared. The baby is in no distress and has no other significant findings on examination.The baby undergoes a full sepsis evaluation, including lumbar puncture. Intravenous ampicillin, gentamicin, and acyclovir therapy is started. An umbilical venous line is placed due to difficulty in obtaining percutaneous venous access.The penile foreskin that was removed during circumcision contains a lesion and is sent to pathology in lieu of a skin biopsy.Erythematous maculopapular rash over entire bodyCongenital self-healing Langerhans cell histiocytosisCongenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare, usually benign, form of Langerhans cell histiocytosis. It was first reported by Hashimoto and Pritzker, who described multiple reddish-brown papulonodules in a newborn girl that showed infiltrating reticulohistiocytes on the skin biopsy and resolved without treatment within a few months. (1) The condition is now alternatively known as Hashimoto-Pritzker disease.The presentation of CSHLCH may mimic other disorders, requiring a thorough evaluation. The other conditions include neonatal hemangiomatosis, (2) congenital infections, pustular melanosis, erythema toxicum, erythropoiesis dermica, and congenital leukemia. (3)In addition to its clinical presentation of a spontaneous eruption of crusted reddish-brown nodules and papules all over the body, the diagnosis is confirmed by pathologic examination of skin containing the papular lesion. Characteristic histologic findings are positive staining for S-100 protein and membranous staining for CD1a antigen in lesional cells. Birbeck granules may also be seen by electron microscopy. Low-density microscopy may show eosinophils or multinucleated giant cells.Kapur and associates(4) published a case series from a 10-year period at Dallas Children’s Medical Center that consisted of 11 cases. All but one of the cases presented at birth; the single other case was diagnosed at 1 month of age. All of the affected infants had only skin involvement at presentation, and all were alive and without evidence of disease at follow-up evaluation.The prognosis for infants who have cutaneous CSHLCH without any other organ involvement is excellent. However, Larralde and associates(5) and others suggest an initial thorough screening evaluation. Such a screening should include a full physical examination; complete blood count; serum chemistry; liver function tests; skull, chest, and long bone radiographs; and abdominal ultrasonography. Bone marrow examination should be performed based on the degree of suspicion of progressive disease. Skin biopsy confirms the diagnosis and is helpful in diagnosing future relapses. Children who have CSHLCH require close follow-up for signs of disease progression, which underscores the importance of making an early diagnosis.JoDee M. Anderson, MD, MEd, Division of Neonatal Medicine, Oregon Health & Science University, Portland, OR.

Index of Suspicion * Case 1: Fever, Barking Cough, Stridor, and Rash in an Infant * Case 2: Erythematous Papulovesicular Rash in a 3-month-old Girl * Case 3: Vomiting and Unrelenting Headaches in a 5-year-old Girl

A 6-month-old boy presents with a temperature of 38.9°C and barking cough of 3 days’ duration as well as a rash over his body for 1 day. On physical examination, his temperature is 37.5°C, respiratory rate is 28 breaths/min, and blood pressure is 87/52 mm Hg. He appears nontoxic and has a barking cough, injected conjunctiva with whitish discharge, dry lips, mild inspiratory stridor, a blanching erythematous maculopapular rash on his trunk and extremities, and small cervical lymph nodes. The rest of his physical findings are normal. His Hgb is 12.8 g/dL (128 g/L), WBC count is 11.7×103/mcL (11.7×109/L) with 75% neutrophils and 23% lymphocytes, and platelet count is 515×103/mcL (515×109/L). His stridor is considered to be due to viral croup, and he is treated with intramuscular (IM) dexamethasone and nebulized racemic epinephrine. A lateral neck radiograph reveals widening of the retropharyngeal space (Fig. 1), and he is started on clindamycin. CT scan of the neck reveals a right retropharyngeal abscess (Fig. 2). He continues to have high spiking fevers and experiences stridor at rest. He is started on IM dexamethasone every 6 hours, and his fever subsides the following day. Figure 1. Lateral neck radiograph showing widening of the retropharyngeal space. Figure 2. CT scan of the neck showing a right retropharyngeal abscess (arrow). On hospital day 6, the corticosteroids are stopped, but the fever returns the following day. Two days later, an erythematous maculopapular rash reappears, and the child’s lips are dry and cracked. On day 10, repeat CT scan shows that the retropharyngeal abscess has resolved. An additional imaging study reveals the cause of his symptoms. A 3-month-old previously healthy girl presents to the ED with a 1-day history of a blistering rash. Her parents noted an erythematous area on her occiput after …

Serum sickness-like reaction associated with meropenem in a 3-year old child

Background Serum sickness-like reactions are typically characterized by fever, arthralgia, rash, and other systemic symptoms within two weeks of antigen exposure. The most common inciting agents are non-protein drugs, most notably cefaclor. This report describes a 3-year old boy who developed a serum sickness-like reaction after receiving a course of meropenem. Materials and methods Laboratory investigations supporting a diagnosis of serum sickness-like reaction were performed. Results A 3 year old with a history of prematurity was treated with intravenous meropenem and vancomycin for a ventriculoperitoneal shunt infection and brain abscess. He developed fever, bilateral knee swelling and an erythematous maculopapular rash to his trunk and extremities on day 14 of meropenem and day 27 of vancomycin. During this time, he had elevated creatinine and C reactive protein, as well as eosinophilia and hematuria. Septic workup was negative, as were tests for autoimmunity. He also developed transient coagulopathy and pancytopenia, felt to be adverse effects of the antibiotics. He was eventually treated with 3 days of intravenous methylprednisolone, and his symptoms improved soon after. The total duration of serum sickness-like symptoms was about 2 weeks. Conclusions

A Rare Case of Malignant T-Cell Non-Hodgkin Lymphoma in a HTLV 1 Carrier With History of Diffuse Large B-Cell Non-Hodgkin Lymphoma

Abstract Introduction Human T-cell leukemia virus type 1 (HTLV-1), a human retrovirus, is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1–associated myelopathy. Infection by HTLV-1 is thought to cause dysregulated T-cell proliferation, which in turn leads to adult T-cell leukemia/lymphoma (ATLL). HTLV-1 is endemic in many geographic regions, principally Japan, the Caribbean, and central Africa. It is also found in Iran, Iraq, southern India, China, the Seychelles, Papua New Guinea, the Solomon Islands, and Australia. This report is a rare known case of diffuse large B-cell non-Hodgkin lymphoma (NHL) who was HTLV-1 carrier from Mashhad of Iran. Case Report A 49-year-old man was admitted to the hospital due to nausea, vomiting, and drowsiness. He had a history of diffuse large B-cell NHL since 14 months ago with involvement of the vallecula, tonsil, base of the tongue, and tip of epiglottis that pathology reviewed two times and immunohistochemistry staining (IHC) showed to be CD20 positive, CD3-negative, and Ki67 50%. He was treated with R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and radiotherapy. He was asymptomatic until about 3 months ago, when diffuse desquamative erythematous maculopapular rashes developed over the skin of his chest, and for 3 weeks he experienced persistently nausea and vomiting and drowsiness that in physical examination was conscious but drowsy. The tongue was very dry, and skin lesions as explained were present. No lymphadenopathy and organomegaly was detected in examinations, and abdominopelvic computed tomography (CT) scans also showed no lymphadenopathy and organomegaly, but thickness of stomach wall was present. Upper gastrointestinal endoscopy showed multiple gastric masses; the largest one was 33 mm that biopsy revealed malignant NHL T-cell type, and immunohistochemistry (IHC) revealed CD3 positive diffusely and scattered CD8 positive. Skin biopsy showed malignant lymphoma diffuse T-cell type, and IHC showed CD3 positive. Both pathologies were reviewed two times by expert pathologists. Peripheral blood smear and bone marrow aspiration and biopsy were normal. Laboratory tests results were serum calcium, 13.5 mg/dL; serum creatinine, 3.87 mg/dL; white blood cell, 12 × 10 9 /L with normal differentiation; hemoglobin, 14.5 mg/dL; and platelet count, 215 × 10 9 /L. He had a history of positive HTLV-1 serology involving himself and 4 members of his family that, repeating in our patient, was again positive. His sister had a history of adult T-cell lymphoma/leukemia 8 years ago with generalized lymphadenopathy and leukocytosis that by IHC has been CD45, CD3, CD5, and CD7 positive, who has been treated as ATLL, and who is now alive. Our patient came from Mashhad of Iran; HTLV-1 infection is endemic for this region. Discussion In this case we could find both B-cell type malignant NHL and typical T-cell-type malignant NHL, both of which being clonal diseases, and adult T-cell lymphoma/leukemia has been etiologically associated with the HTLV-1 virus. Human T-cell lymphotropic (HTLV) viruses are retroviruses that predominantly infect CD4 and CD8 cells, respectively. HTLV-1 is transmitted by the following routes: sexual, parenteral, by way of blood product transfusion, contaminated needles and syringes and vertically, through maternal milk. Other diseases may be associated with HTLV-1, including arthropathies, pneumopathies, uveitis, and dermatologic diseases. However, most patients infected with HTLV-1 remain an asymptomatic carrier throughout their lifetime. ATLL is more common in areas where HTLV-1 is endemic. Patients with ATLL are usually infected before the age of 20 years, and their relatives have a high prevalence of HTLV-1 infection. The disease does not usually appear in more than 1 member of the family. Epidemiologic studies focusing on ATLL demonstrate that some 2% to 4% of infected patients develop neoplasia after a latent period of 20-30 years. Although there is a long latency, carriers have a 1%-5% chance of developing ATLL, thus making ATLL more common in areas where HTLV-1 is endemic, a condition frequently complicated by marked and refractory hypercalcemia, and with a poor prognosis. The cutaneous manifestations of ATLL are common and have different types of lesions. Results Association between HTLV-1 and T-cell lymphoma-leukemia has been reported many times, but appearance of B-cell and T-cell type NHL in one patient is a very rare condition that has been reported rarely; also 5 members of his family were infected by this virus. More investigations need to assess the relationship between these types of diseases.

A young woman with episodic angioedema, papilledema, and eosinophilia

A 21-year-old Chinese woman presented to the Emergency Department with a 6-week history of progressive headache, blurred vision, exertional dyspnea and limb claudication, mild epistaxis, and heavy menses. This was preceded by a 15-month history of episodic erythematous maculopapular rash and limb swelling. She had no fever, weight loss, or night sweats. Her past history was significant for glucose-6-phosphate dehydrogenase (G6PD) deficiency and she was on nortriptyline for headaches. She was not sexually active, had not traveled, and used no recreational substances. This syndrome of headache, visual disturbance, claudication, and mucosal bleeding suggests disruption of the microvasculature and platelet dysfunction such as seen in hyperviscosity syndrome. Increased serum viscosity may be due to hypergammaglobulinemia (monoclonal or polyclonal) or cryoglobulinemia and may lead to neurologic defects, mucosal bleeding, and thrombosis. Increased cellular viscosity is seen in conditions such as acute leukemia (leukostasis), myeloproliferative neoplasms, or sickle cell crisis and typically affects small vessels of the lungs and brain. The limb claudication, neurologic symptoms, and skin rash may also indicate a systemic vasculitis. Her transient limb swelling suggests angioedema. G6PD deficiency is typically an X-linked recessive disorder and therefore unusual in females but a hemolytic workup is appropriate if she is anemic. Physical examination revealed a pale thin young woman. Her temperature was 36.88C, blood pressure 115/65 mmHg (no pulsus paradoxus), heart rate 130 beats per minute, respiratory rate 20 breaths per minute, and oxygen saturation 98% on ambient air. Head and neck examination revealed multiple bilateral 1–2 cm soft, mobile cervical lymph nodes. Her jugular venous pressure (JVP) was at the angle of her jaw while at 908 and she had a loud pulmonic component of the second heart sound (P2), but no right ventricular heave. Her liver edge was palpable 6 cm below the costal margin, the span was 18 cm by percussion, and there was no splenomegaly. Fundoscopy revealed papilledema with tortuous ‘‘sausage’’ vessels, indistinct optic disk margins and absence of arterial pulsations. The rest of her neurologic exam was unremarkable. She had no rash, swelling, or joint effusions. Bloodwork done 1 week before revealed white-cells 13.9 3 10 per liter, eosinophils 3 10 9.1 3 10 per liter (normal 0.7), hemoglobin 75 g per liter, platelet count 205 3 10 per liter, total protein 137 g per liter (normal 62–82), albumin 31 g per liter, and gamma globulin 91 g per liter (normal 5.1–15) with a focally increased gamma-globulin peak. Immunofixation revealed predominantly IgG with corresponding lambda and kappa light chain bands of equal intensity. Creatinine was 82 lmol per liter, and urine was negative for blood and protein. An abdominal ultrasound 1 week before showed mild hepatomegaly of 17.9 cm with porta-hepatis lymphadenopathy measuring up to 2.7 cm, but no splenomegaly and no other intra-abdominal lymphadenopathy. The markedly elevated immunoglobulin G (IgG) levels and papilledema confirm the hypothesis of hyperviscosity syndrome. Equal kappa and lambda light chain intensity indicates a polyclonal gammopathy, although with such high levels, a monoclonal element cannot be excluded. Structural causes of raised intracranial pressure must be ruled out. Polyclonal hypergammaglobulinemia and eosinophilia may be associated with connective-tissue disease such as the Churg-Strauss syndrome, lymphoproliferative disorders such as angioimmunoblastic T-cell lymphoma (AILT), and idiopathic eosinophilia. Malignancy and parasitic infection with multiorgan involvement (such as strongyloides stercoralis) should be ruled out. Medication reactions, atopic disease, and adrenal insufficiency may be associated with reactive eosinophilia and/or hypergammaglobulinemia but are unlikely in this case. She has evidence of pulmonary hypertension with right ventricular failure (elevated JVP, loud P2, and hepatomegaly). This may be related to hyperviscosity. Hyperviscosity increases the risk of vascular thrombosis, so an electrocardiogram and cardiac enzymes should be done, as well as a computed tomography pulmonary angiogram to rule out

Facial palsy in a 2-month-old infant with Kawasaki disease

An 8-week-old breast-fed female infant had high-grade fever for 2 weeks. Despite multiple oral and intravenous antibiotics, there was no fever defervescence. She developed irritability, refusal to feed and facial deviation towards right side 2 days prior to referral to our hospital. On examination, she was febrile, extremely irritable, tachypneic and had pallor, left sided infranuclear facial nerve palsy (FNP) with hepatosplenomegaly. The ear, ocular and the rest of the systemic examination were normal. Investigations revealed normocytic-normochromic anemia, leucocytosis (25.1 £ 10/L, 70% neutrophils), thrombocytosis (7.86 £ 10/L), hypoalbuminemia (2.8 gm/dl), positive C-reactive protein (249.9 mg/dl), normal urine examination and chest X-ray. Lumbar puncture showed 30 cells (65% polymorphs), glucose of 63 mg/dl, protein of 71 mg/dl. Blood, urine, CSF and stool cultures were sterile. Computerized tomography of head was normal. Child was commenced on broad spectrum intravenous antibiotics with supportive treatment. She developed erythematous maculopapular rash involving the face, trunk, and extremities that was initially considered ‘drug-rash’. Thereafter, the infant developed nonpurulent conjunctivitis. In view of these, a possibility of Kawasaki disease (KD) was entertained. A 2D-Echo showed dilatation of right (8 mm) and left (6 mm) coronary arteries and left anterior descending artery (6 mm) with minimal pericardial eVusion. Treatment with intravenous immunoglobulin (IVIg) (2 g/kg) and aspirin (75 mg/kg per day) was initiated. Within 24 h, there was resolution of fever and irritability. The facial nerve palsy resolved over next 2 days (Fig. 1). FNP is a rare manifestation of KD with less than 35 cases reported so far [1]. The age of reported patients ranges from 3 to 25 months. We report the youngest such infant till date. Atypical KD analogous to our case is more common in young infants and is associated with worse coronary outcomes [2]. The above case emphasizes that possibility of KD must be considered in a patient of any age with unexplained prolonged fever, even with incomplete diagnostic features and unusual manifestations like FNP for timely diagnosis and apt treatment. Appearance of rash should further alert the clinician. FNP in KD shows a female preponderance (1.4:1) with predominant left sided involvement [3, 4]. The inXammatory

Parvovirus B19 Infection Associated With Acute Hepatitis in Infant

To the Editors: Human parvovirus B19 (B19) infection shows a wide spectrum of cutaneous manifestations and systemic involvements, especially in adults. Acute hepatitis and hepatic disorders are rare, however, and there are only 2 reports of B19 infection associated with acute hepatitis in adults in the English literature.1,2 To our knowledge, the case reported in this article is the first case of B19 infection associated with acute hepatitis in an infant. A 9-month-old female infant presented at our hospital with high-grade intermittent fever (39°C) for 6 days, associated with erythematous maculopapular nonpruritic rash. Her parents denied any drug intake or exposure to children or adults with exanthematous diseases. Erythematous maculopapular rashes were present over the entire body, excluding the palms and soles. The rash first appeared on the face within 12 hours of the onset of fever, and later spread to the trunks and limbs. After 7 to 10 days, a central clearing appeared in the rash that had a lace-like or reticular appearance especially on the cheeks, which looked like “slapped-cheek.” There was no hepatosplenomegaly or palpable lymph nodes. As the symptoms and signs suggested erythema infectiosum, we asked for the consent of the parents of the patient to perform further evaluations to determine the causative agent. We conducted normal tests such as a full blood count, measurement of the prothrombin time and the muscle enzymes, and urinalysis. The serum alanine aminotransferase level was 4745 U/L (normal level: 10–35), the aspartate aminotransferase level was 3428 U/L (normal level: 5–38), and the lactate dehydrogenase level was 825 U/L (normal level: 106–211). The serologic tests for cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and hepatitis A, B, C, and E viruses were all negative. Enzyme-linked immunosorbent assay revealed anti-B19 IgM 5.77 (normal level: <0.8) and IgG 0.61 (normal level: <0.8) antibodies. Using the polymerase chain reaction (Chung-Ang University Hospital Laboratory, Seoul, Korea), the serum was positive for B19. Based on these clinical features and investigations, the patient was finally diagnosed to have erythema infectiosum with acute hepatitis. The patient was treated with antipyretics and rest. The skin eruption cleared in 10 days without desquamation, and the aminotransferase values became normal within 14 days. Three weeks later, the anti-B19 enzyme-linked immunosorbent assay had changed to IgM 0.41 (normal level: <0.8) and IgG 9.40 (normal level: <0.8). B19 infection has a worldwide distribution, with school outbreaks in late winter and early spring. It affects primarily the 4- to 10-year age group. Although the disease is self-limiting, systemic features with B19 infection make its diagnosis important.3 Systemic features are severe in adults, including arthralgia with synovitis and rarer manifestations such as aplastic crisis in patients with chronic hemolytic anemia, bone marrow failure in immunocompromised hosts, a transient febrile myasthenia-like syndrome, myositis, and acute heart failure. These occur rarely in infants.4 B19 infection is associated with a wide spectrum of clinical manifestations, including erythema infectiosum, rubilliform rashes, the Gianotti-Crosti syndrome, Henoch-Schönlein purpura, the papular purpuric gloves-and-socks syndrome, and erythema multiforme. The best known of these is erythema infectiosum, or fifth disease, which classically occurs with childhood infections.3,4 Erythema infectiosum is characterized by confluent erythematous and edematous patches or plaques on the cheeks, which spare the nasal bridge and periorbital regions. The rash spreads to the trunk and extensor extremities, which undergo patchy clearing that results in a lace-like reticular pattern. Occasionally, mild prodromal symptoms precede the rash, which include low-grade fever, headache, pharyngitis, malaise, myalgias, nausea, diarrhea, and joint pain.5 To our knowledge, there are only 2 reports of B19 infection, both in adults, associated with acute hepatitis in the English literature.1,2 We documented a case of erythema infectiosum with acute hepatitis in a 9-month-old infant associated with B19 infection. This is the first report of such infection in an infant in English literature. Beom Joon Kim, MD Kwang Ho Yoo, MD Kapsok Li, MD Myeung Nam Kim, MD Department of Dermatology College of Medicine Chung-Ang University Seoul, Korea

Severe cutaneous reaction to cetuximab with possible association with the use of over-the-counter skin care products in a patient with oropharyngeal cancer

Background: The management of locally advanced head and neck cancer remains a challenge to most oncologists and their patients. Treatment with epithelial growth factor receptor inhibitors (EGFRIs) is associated with a good response. Cetuximab, a chimeric monoclonal antibody directed against epithelial growth factor receptor (EGFR), in combination with radiation therapy is indicated for the treatment of locally advanced squamous cell carcinoma of the head and neck. Although a mild acneiform skin rash (Grade 1, 2) is very common in these patients, severe rash (Grade 3) is uncommon.Case report: A 61-year-old African American man with locally advanced oropharyngeal cancer was treated with cetuximab and radiation. He developed a sudden flare-up of a skin rash after the 5th cycle of cetuximab following use of over-the-counter (OTC) skin care remedies. The rash manifested with severe maculopapular eruption and erythematous rash, along with desquamation and exfoliation of the skin, mainly on the face and neck area. The patient denied any extraordinary sun exposure. Cetuximab and radiation therapy were held for 1 week and the rash was treated with doxycycline, diphenhydramine, and continued use of natural emollient (Vaseline petroleum jelly). After 1 week, a dramatic improvement of the facial rash was noticed.Discussion: Our report describes a sudden flare-up of a skin rash (Grade 3) after the 5th cycle of cetuximab following use of OTC skin care remedies, which was unusual for this patient, suggesting a possible relation to the therapy. Skin crucially depends on EGFR for its normal function and becomes extremely sensitive during cetuximab therapy. Topical OTC acne and dry skin remedies can suddenly change the mild acneiform rash into severe skin toxicity associated with marked desquamation and exfoliation. Avoidance of further skin damage caused by topical applications and the use of doxycycline and diphenhydramine show a significant success in the management of skin toxicity.

Cutaneous manifestations in patients suspected of chikungunya disease

Context:An epidemic of chikungunya disease occurred in India during late 2005 through 2006 affecting nearly 1,400,000 people.Aim:To study the cutaneous manifestations in suspected cases of chikungunya disease.Settings and Design:Patients who attended our outpatient departments from January 2006 to September 2006 were prospectively included if they had symptoms of chikungunya disease according to the ‘case definition’ of the National Institute of Communicable Diseases, Directorate General of Health Services, Government of India. The criteria were an acute illness characterized by the sudden onset of fever and several symptoms such as joint pain, headache, backache, photophobia, and eruption during an epidemic of chikungunya fever in the absence of confirmatory serological tests.Materials and Methods:A total of 115 patients (65 men and 50 women) who satisfied the above criteria were enrolled for the study.Results:An erythematous maculopapular rash subsiding without any sequelae in 3-4 days was the most common cutaneous finding in our patients. Genital ulcers distributed predominantly over the scrotum and base of the penile shaft in men and labia majora in women were the second most common manifestation. Other manifestations included tenderness/edema of hands and feet, grouped hyperpigmented macules over the nose and cheeks, fixed drug eruptions, erythema nodosum, erythema multiformae, generalized urticarial eruptions, and flare up of pre-existing psoriasis and lichen planus.Conclusions:To conclude, a plethora of cutaneous manifestations were noted in suspected cases of chikungunya disease. Genital ulcers, to the best of our knowledge, have not been reported during the earlier epidemics but have been reported by others during the present one.

Drug-induced hypersensitivity syndrome associated with reactivation of human herpesvirus6 presenting with severe hepatic injury.

Little is known about the pathophysiology of liver complication seen in drug-induced hypersensitivity syndrome (DIHS). We describe herein a 32-year-old Japanese man with DIHS due to salazosulfapyridine (SASP) associated with reactivation of human herpesvirus6 (HHV-6) presenting with severe acute hepatic injury. The patient, with a 1-year history of ulcerative colitis (UC), presented with high fever and abnormally elevated liver enzymes. Six weeks prior to his symptoms, prednisolone (PSL) and SASP had been started because of UC aggravation. Besides fever and liver dysfunction, the appearance of atypical lymphocytes together with eosinophils and generalized erythematous maculopapular skin rash developed sequentially, and a diagnosis of DIHS was established. Despite cessation of SASP and increased dose of PSL, his initial abnormalities continued, and biphasic second alanine aminotransferase (ALT) flare with deep jaundice worsened. Based on the significant increase in the titer of HHV-6 IgG antibodies at the second peak of ALT level without HHV-6 IgM antibody elevation, strongly suggesting reactivation of the virus, HHV-6 was first considered to directly contribute to the deterioration of liver function. However, extensive histological analysis of the liver led to the realization that the cause of the DIHS liver injury was essentially drug-related hepatotoxicity induced by SASP, causing wide-ranging damage to both the hepatocytes and cholangiocytes.

Cutaneous presentation of aleukemic monoblastic leukemia cutis – a case report and review of literature with focus on immunohistochemistry

Aleukemic monoblastic leukemia cutis is a rare cutaneous manifestation of a systemic hematological disorder associated with dermal infiltration of monoblasts preceding bone marrow or peripheral blood involvement. We report a case of a 75-year-old woman who presented with an erythematous maculopapular rash, which was clinically diagnosed as viral exanthema. Microscopy of the skin biopsy showed features of monoblastic leukemia. Her general physical condition rapidly deteriorated and she died 4 weeks later. We present this case to alert dermatologists of innocuous erythematous skin lesions clinically resembling a viral exanthema, which, in rare instances, may be a presenting feature of an aleukemic monoblastic leukemia cutis. This entity poses problems for dermatopathologists even on immunohistochemistry as monoblasts are negative for hemopoietic precursor cell antigens like CD34, Terminal deoxynncleotidy1 transferase (TdT) and CD117.

Nonbloody, Red Stools from Coadministration of Cefdinir and Iron‐Supplemented Infant Formulas

Cefdinir is an extended-spectrum, third-generation cephalosporin that may be used for treatment of acute otitis media in patients allergic to penicillin. When administered with iron-containing products, including infant formulas, cefdinir or one of its metabolites may bind to ferric ions, forming a nonabsorbable complex that imparts a reddish color to the stool. We describe a 9-month-old infant with failure to thrive and acute otitis media who developed an erythematous maculopapular rash during treatment with amoxicillin-clavulanate. His antibiotic therapy was changed to cefdinir. Five days into a 10-day course of therapy, the infant's mother brought him to the pediatric clinic and reported the appearance of red stools. He had no associated gastrointestinal symptoms (vomiting, abdominal pain, or diarrhea). His hematocrit and hemoglobin level were normal, and Clostridium difficile antigen studies and tests for species of Shigella, Salmonella, and Camphylobacter as well as ova and parasites were all negative. Cefdinir was discontinued, and his stools returned to normal within 48 hours. Three weeks later, he again received cefdinir for recurrent otitis media. Red stools reappeared 48 hours later, were determined to be guaiac negative, and resolved within hours of drug discontinuation. During both occurrences of red stools, the infant had been breastfed and was receiving supplemental feedings with an iron-containing infant formula. In the product labeling of cefdinir, this adverse event is described as a consequence of the drug-drug interaction; however, it is not listed in the adverse drug reaction section of the labeling. As such, one may miss the association between cefdinir and reddish stools when investigating this event as a potential adverse reaction to cefdinir. When using the Naranjo adverse drug reaction probability scale to assess causality in our patient's case, this adverse drug reaction was determined as highly probable. As this infant had been breastfed, the use of a supplemental iron-containing infant formula was not identified as a potential contributing factor until the second occurrence of red stools. Health care professionals should review the entire product labeling, including the drug-drug interaction section, when investigating a potential adverse drug reaction. With the recent approval of generic formulations of cefdinir, clinicians should be aware of this drug-drug interaction with iron-containing products to prevent unnecessary alarm by parents and caregivers, as well as costly medical evaluations for gastrointestinal bleeding.