Cutaneous Rash Research Articles

38 Cutaneous rash with elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis

38 Cutaneous rash with elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis

A Spotlight on Drug-Induced Vasculitis.

Drug-induced vasculitis (DIV) is a rare form of vasculitis related to the use of various drugs. DIV primarily affects small to medium size vessels, but it can potentially involve vessels of any size. Differentiating between primary systemic vasculitis and DIV can be challenging; however, it is crucial, so that the offending agent can be discontinued promptly. The clinical phenotype of DIV is protean and depends on the size of the affected vessels. It ranges from arthralgias, to an isolated cutaneous rash, to severe single or multi-organ involvement. While withdrawal of the offending drug is the most important step in management, a significant number of patients require immunosuppressive therapy for varying periods of time. DIV can affect any vascular bed size, leading to protean vasculitic syndromes. Increased awareness among general practitioners, specialty, andsubspecialty physicians is crucial for early recognition, and withdrawal of drug for better outcomes.

Prenatal and Postnatal Zika Intrauterine Infection: Diagnostic Imaging Techniques and Placental Pathology

Introduction: Zika virus (ZIKV) is an arbovirus (arthropod-borne virus) in the genus Flavivirus and Flaviviridae family. In November 2015, several cases of microcephaly in Northeastern of Brazil suggested ZIKV involvement. Case Report: A 33-year-old primigravida developed fever and cutaneous rash at 7th week of gestation (WGA). The ultrasound and MRI examination showed head circumference < 5th centile and enlargement of lateral ventricles. The infant was delivered at 39th WGA with microcephaly. Microscopy of the placenta showed chronic villitis and intervillitis, nodular stromal fibrosis in the stem villi, and vascular thickening. Postnatal CT showed collapsed cranium due to growth impairment of the suprathalamic brain, multiple cerebral calcifications, parenchymal atrophy, and ventricular dilatation. Now, at 6 years old, the child suffers from severe neurologic symptoms, including seizures. Conclusion: This case gathers images of prenatal and postnatal period, and placental histopathology. The long-term follow-up highlights the dramatic neurological sequelae induced by ZIKV.

Acute abdomen due to anaphylactic intestinal edema associated with systematic mastocytosis: a case report

BackgroundAmong various anaphylactic conditions resulting in acute abdomen, mast cell activation disorders, although rare, are included in the differential diagnosis.Case presentationThis report describes a 63-year-old Caucasian man who was brought to the emergency room with sudden onset abdominal pain, vomiting, and diarrhea, with breathing difficulty, and with facial swelling after quarrelling with an acquaintance. Computed tomography showed edematous and swollen intestines, consistent with splenomegaly. Physical findings included maculopapular cutaneous mastocytosis. He also had a long history of repeated episodes of anaphylaxis requiring occasional epinephrine auto-injector administration; however, the precise cause of anaphylaxis was previously undetermined. Blood tests showed high serum concentrations of soluble IL-2R and tryptase, suggesting mast cell-related disease. Subsequent biopsies of his bone marrow and cutaneous rash confirmed the diagnosis of systemic mastocytosis (SM).ConclusionSM was diagnosed in a patient with acute abdomen who visited the emergency room.

Toxidermie type exanthème maculo-papuleux secondaire au vaccin Sinopharm-CoronaVac®

IntroductionChinese Sinopharm-CoronaVac® vaccine is safe and well tolerated, its skin reactions are rarely reported. We report the case of a cutaneous adverse reaction due to this vaccine. ObservationA 32-year-old female with no remarkable medical history. She was admitted for a generalized itchy maculo-papular rash appearing 4 days following the administration of the first dose of the Sinopharm-CoronaVac®. The causality reveals a possible association between the vaccine and the drug reaction. DiscussionPublished data from randomized trials Phase I and II trials have shown that the Sinopharm-CoronaVac® has good immunogenicity, safety and tolerability in the majority of patients with few reported adverse events. In literature, we found only one case that developed a cutaneous rash due to Sinopharm-CoronaVac® vaccine but without any precisions. ConclusionWe report the first case of a cutaneous adverse reaction type Maculopapular rash after the first dose of the Sinopharm-CoronaVac® vaccine.

S208: EFFICACY AND SAFETY OF ZANDELISIB ADMINISTERED BY INTERMITTENT DOSING (ID) IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) FOLLICULAR LYMPHOMA: PRIMARY ANALYSIS OF THE GLOBAL PHASE 2 STUDY TIDAL

Background: Zandelisib, a PI3Kδ inhibitor with high target-binding affinity, is administered by intermittent dosing (ID) on days 1 to 7 of 28-day cycles to potentially enable regulatory T-cell repopulation and lower the risk of immune-related adverse events (irAEs) associated with continuous PI3Kδ inhibition. In a phase 1b study in 37 patients (pts) with R/R FL, zandelisib administered daily for two 28-day cycles for tumor debulking then on ID achieved an overall response rate (ORR) of 87% (78% as single agent and 95% with rituximab), a median duration of response (DOR) not reached at median follow-up of 16.9 months, and a low rate (<10%) of grade 3 irAEs (Pagel et al. ICML 2021; #113). Aims: We conducted the TIDAL study (NCT03768505) to further evaluate in a global trial the efficacy and safety of zandelisib in larger group of pts with R/R FL and marginal zone lymphoma (MZL). The MZL cohort is still enrolling and not reported here. Methods: Eligible pts ≥18 years with FL Grade I-IIIA, ECOG performance status 0-1, progressive disease after ≥2 prior therapies including an anti-CD20 antibody and chemotherapy, and no prior PI3Kδ inhibitor, provided consent and then received zandelisib 60 mg daily for two 28-day cycles then on ID. Another study arm evaluating zandelisib 60 mg daily continuously was closed to enrollment early and is not reported here. The planned sample size in FL was 120 pts on ID, with the primary efficacy population (PEP) pre-defined as the first 91 pts treated and the safety population consisting of all FL pts treated. The primary efficacy endpoint was ORR as assessed by independent review using the Lugano criteria and analyzed 6 months after completing enrollment in the PEP. Results: 121 FL pts were enrolled. In the PEP (N=91 pts), the median number of prior therapies was 3 (range 2-8), 21 pts (23%) have received prior stem cell transplant, 42 pts (46%) were refractory to last therapy, 31 pts (34%) had tumors ≥5 cm, and 51 pts (56%) were POD24. The ORR was 70.3% (N=64) (95% CI 59.8-79.5%), with 32 pts (35.2%) achieving a complete response (CR). Responses occurred early, with 85.5% (N=56) achieved in the first 2 cycles of therapy and 75% of CRs (N=24) achieved the first 4 cycles. The data are still immature to estimate accurately the DOR. With a median follow-up of 9.4 months (range 0.8-24) in the safety population of 121 pts, 12 pts (9.9%) discontinued therapy due to any drug-related AE. Grade 3 AEs of special interest (AESI) were diarrhea in 6 pts (5%), colitis in 2 (1.7%), cutaneous rash in 4 (3.3%), stomatitis in 3 (2.5%), and 1 (0.8%) each for AST and ALT elevation, and non-infectious pneumonitis. Grade 3 AESIs primarily (15 of 18, 83%) occurred in cycles 1-3, during daily dosing, with only 3 cases reported on ID in Cycles ≥4. Summary/Conclusion: Zandelisib on ID achieved high ORR (70.3%) and CR rate (35.2%) in heavily pretreated R/R FL pts, and was associated with a low rate (<10%) of grade 3 AESI and discontinuations due to AEs, results comparable to the Phase 1b study. Longer follow-up is needed to estimate median DOR. This profile supports evaluation of zandelisib as a single agent and in combination regimens in various B-cell malignancies, both in R/R disease and in earlier lines of therapy. Zandelisib plus rituximab vs chemoimmunotherapy is being evaluated in the phase 3 study COASTAL in R/R FL and MZL (NCT04745832).

Safety and efficacy of Ibrutinib in Indian patients with chronic lymphocytic leukemia.

e19585 Background: Ibrutinib, an oral Bruton's tyrosine kinase inhibitor, is approved for the treatment of chronic lymphocytic leukemia (CLL) in both upfront and relapsed/refractory. The prevalence of CLL is very low in India compared to western countries. Hence, the real-world data regarding efficacy and safety of Ibrutinib among the Indian population is very scarce. In this study, we aim to examine the toxicity profile, treatment response, and survival outcomes among Indian patients with CLL treated with Ibrutinib. Methods: In this retrospective study, we recruited all consecutive patients diagnosed with CLL, both treatment naïve (TN) and relapsed/refractory (R/R) CLL, on Ibrutinib (daily dose of 420 mg), registered at the Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India between April 2016 and December 2021. Diagnosis of CLL, an indication of treatment, and response assessment were based on the recent guidelines (2018) from the International Workshop on CLL (iwCLL). Results: A total of 90 patients were recruited in this study, of which 33 were newly diagnosed and 57 had R/R CLL. Median age of the cohort was 60 years (range, 35–80 years) and male to female ratio was 3:1. The median total leukocyte count was 55x109/L and Del 17p was detected in 18% of cases. The R/R cases had received a median of 1(1-3) prior line of therapy. Overall response rate was observed in 76(84.4%), complete response was in 18 (20%) cases, partial response (PR) was in 49 (54.4%) cases, and in 9 (10%) cases PR with lymphocytosis (PR-L) was observed. With a median follow-up period of 15 months (4-60), 2-year progression-free survival (PFS) was 80% for the whole cohort. The median PFS was not reached in TN cases and was 18 months in R/R cases. Grade-3/4 adverse events (A/E) were seen in 17 (29.8%, n = 57) of R/R cases and in 3 (9.1%,n = 33) of TN cases. The most common Grade-3/4 A/E were infections in 19 (21.1%), (Varicella: 7, Pneumocystis: 6, Aspergilosis: 2, Mucormycosis: 1, Disseminated tuberculosis: 1, Encephalitis: 1, Others: 1) and cytopenias in 9 (10%) of cases. Other A/E were fatigue in 6 cases, arthralgia in 3, bleeding in 2, cutaneous rash in 2, reactivation of hepatitis-B in 2, diarrhea in 2, arrhythmia in 2, and autoimmune hemolytic anemia in one case. Ten patients (11.1%) had a dose reduction due to AE. The discontinuation rate was 27 (30%), due to progressive disease in 18 patients and due to adverse events in 9 patients. Twenty patients died, 14 due to disease progression or Richter's transformation, 5 due to infections, and 2 due to other reasons. Conclusions: This is the largest study of ibrutinib from India. Ibrutinib is safe and effective in upfront and R/R cases of CLL. Infections are the most common adverse event in R/R cases. Acyclovir and Co-trimoxazole prophylaxis can be considered in R/R cases of CLL in routine clinical practice . Arrhythmias were rare A/E as compared with the available literature.

SARS-CoV-2 vaccine-related cutaneous manifestations: a systematic review.

To date, over 250 million people have been reportedly infected by COVID‐19 disease, which has spread across the globe and led to approximately 5.1 million fatalities. To prevent both COVID‐19 and viral transmission, DNA‐based/RNA‐based vaccines, non‐replicating viral vector vaccines, and inactivated vaccines have been recently developed. However, a precise clinical and histological characterization of SARS‐CoV‐2 vaccine‐related dermatological manifestations is still lacking. A systematic review of 229 articles was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, in order to provide an extensive overview of SARS‐CoV‐2 vaccine‐related skin manifestations. Data on demographics, number of reported cases with cutaneous involvement, vaccine, and rash type (morphology) were extracted from articles and summarized. A total of 5941 SARS‐CoV‐2 vaccine‐related dermatological manifestations were gathered. Local injection‐site reactions were the most frequently observed, followed by rash/unspecified cutaneous eruption, urticarial rashes, angioedema, herpes zoster, morbilliform/maculopapular/erythematous macular eruption, pityriasis rosea and pityriasis rosea‐like eruptions, and other less common dermatological manifestations. Flares of pre‐existing dermatological conditions were also reported. Cutaneous adverse reactions following SARS‐CoV‐2 vaccine administration seem to be heterogeneous, rather infrequent, and not life‐threatening. Vaccinated patients should be monitored for skin manifestations, and dermatological evaluation should be offered, when needed.

Acute cerebral infarction due to severe COVID-19, bacterial meningitis due to Pseudomonas stutzeri, mild loculated pericardial effusion due to MIS-C

Neurological involvement was common in children and adolescents with Coronavirus disease-2019 (COVID-19) related hospitalization and is mostly transient. A spectrum of life-threatening neurologic involvement infrequently occurred and was associated with more extreme inflammation and severe sequel. We reported a patient male, seven months old with chief complaint of fever since 1 month before admission. The patient was diagnosed by confirmed case COVID-19 with a positive RT-PCR SARS-CoV-2 swab. He had some contact with his parents that had confirmed with COVID-19 before. The patient also complained with focal seizures in the left extremity with decreased of consciousness. The seizure always repeated every day for 1 week with the same pattern. Patient also complain of nausea and vomiting every time he has been breastfed. There is no changes of the lips and oral cavity, no cutaneous rash, no red eyes, no swelling or edema on extremities. Non-contrast head CT-Scan revealed large area of acute cerebral infarction. Echocardiography revealed mild loculated pericardial effusion and cerebrospinal fluid cultured result revealed Pseudomonas stutzeri. After 3 weeks discharged from the hospital, the patient underwent a head MRI examination and the results revealed chronic ischemic cerebral infarction and communicating hydrocephalus. The patient was planned to undergo a VP shunt as a treatment for hydrocephalus. The neurological involvement can occur in children and adolescents with COVID-19. The range of severe neurologic complications including peripheral nerve disorders, focal CNS disease and diffuse CNS involvement, make it likely that multiple mechanisms underlie this wide spectrum of disease.

Acute Syphilitic Hepatitis in the Early Secondary Phase: A Case Report and Literature Review

Background: The incidence of syphilis is clearly increasing. It is a source of visceral damage, particularly in the secondary phase. Acute syphilitic hepatitis is a rare clinical entity classically described but under-diagnosed because of its non-specific presentation. Case Presentation: We report the case of a 25-year-old French woman, without comorbidity, sexually active, having unprotected sex with only one partner. She was admitted to our unit for jaundice and a disturbed liver function test preceded 3 weeks earlier by a rash. The patient did not consume alcohol and did not report the introduction of a new medication. A skin rash compatible with syphilitic roseola and generalized adenopathy were found. The liver workup showed alanine aminotransferase (ALT) at 1984 U/L, aspartate aminotransferase (AST) at 1377 U/L, total bilirubin at 221 μmol/L, alkaline phosphatase activity (APL) at 419 U/L, gamma glutamyl transferase activity (GGT) at 229 U/L and a prothrombin concentration at 73%. The search for the most common etiologies of acute hepatitis was negative. Syphilitic serology was positive with a Treponema Pallidum Hemagglutinations Assay (TPHA) titration of 5120 IU and Veneral Disease Research Laboratory (VDRL) of 64 IU. Abdominal ultrasound revealed only homogeneous hepatomegaly and splenomegaly with no focal lesions. Other sexually transmitted infections (STI) were negative and her partner had positive syphilis serology. After a single dose of Benzathine benzylpenicillin, the clinical signs regressed after one week and the hepatic balance tended to normalize 20 days later. Conclusion: This highlights the need for a high index of suspicion for syphilitic hepatitis in sexually active patients presenting with acute hepatitis associated with a cutaneous rash.

COVID-19 associated Kawasaki-like multisystem inflammatory syndrome in an adult

Recently, few reports have described a serious condition linked to SARS-CoV-2 that mimics Kawasaki disease called multisystem inflammatory syndrome, especially in children (MIS-C) and young adults. In this work, we report on a severe form of MIS in a young female adult previously infected by SARS-CoV-2. She was treated by plasmapheresis with albumin and steroids, however outcome was fatal. We discuss the pathogenesis of this rare and life threatening entity and suggest some therapeutic regimen. This syndrome should not be misdiagnosed with an infectious or a drug induced cutaneous rash in the current context of COVID-19 pandemic.

Long-Term Efficacy and Safety of Ibrutinib in the Treatment of CLL Patients: A Real Life Experience.

Ibrutinib has demonstrated a significant clinical impact in patients with de novo and relapsed/refractory chronic lymphocytic leukemia (CLL), even in cases with unfavorable cytogenetics and molecular markers. All CLL patients’ data treated at our Institute with ibrutinib have been retrospectively reviewed. Forty-six patients received ibrutinib either as frontline (10) or second or more advanced treatment (36). Five patients presented with TP53 mutations; 11 had the deletion of chromosome 17p; 17 displayed an unmutated immunoglobulin variable heavy chain status. The median number of cycles administered was 26. Among patients treated frontline, the best overall response rate (ORR) was 90.0%. In patients receiving ibrutinib as a second or later line ORR was 97.2%. Median progression-free survival was 28.8 and 21.1 months for patients treated frontline and as second/later line, respectively. Median overall survival was not reached for those treated frontline and resulted in 4.9 years for patients treated as second/later line. Grade 3–4 hematological toxicities were neutropenia, thrombocytopenia, and anemia. Grade 3–4 extrahematological toxicities included diarrhea, cutaneous rash, utero-vesical prolapse, vasculitis, and sepsis. Ibrutinib is effective and well tolerated in CLL. Responses obtained in a real-life setting are durable and the safety profile of the drug is favorable.

DENGUE FEVER- A WORLDWIDE STUDY

Nowadays, after coronavirus COVID 19, dengue fever is a problem of human beings that is spread by the Aedes aegypti mosquitoes. If proper protection arrangements from the particular mosquitoes are not done, this problem may lead to a pandemic. The main problem of this fever is that the starting symptoms are the same as viral fever as high fever, myalgia, muscular and joint pain, hemorrhagic episodes, and cutaneous rash. The purpose of this manuscript is to aware people of this health problem. Near the rain season, the problems of mosquitoes are increased. The awareness of the people could prevent this disease. In this manuscript, an analytic study on the worldwide dengue fever has been made. It is observed that after 2010, the cases of dengue fever are increased continuously. People should keep neat and clean their surroundings and cover maximum part of the body.

Life-threatening reaction of a pediatric cancer patient to sodium hypochlorite

The use of sodium hypochlorite (NaOCl) as irrigation solution in endodontics is widespread and accidents of apical extravasation may occur, being in most cases mild to moderate situations of simple management. However, in immunosuppressed patients, the reaction may be exacerbated, with significant systemic changes and potentially life-threatening. Even so, there is a lack of information about the management of these special cases, especially in oncopediatric cases. Therefore, the aim is to report a case of severe reaction post-accident with NaOCl in a 13-year-old adolescent undergoing chemotherapy, with significant edema, gingival necrosis, cutaneous rash, edema of the extremities, pleural effusion, and bronchopneumonia, with a 30-day evolution. It is understood that several factors, including anatomical, may predispose this situation, which can occur even with expert and experienced professionals, not necessarily associated with poor practice. The authors raise the importance of further studies to discuss the real need and indication of the use of NaOCl as an irrigating solution for these patients and suggest the adoption of extra safety measures to avoid the occurrence of similar situations.

Pseudoangioedema in dermatomyositis patients indicates severe disease and poor prognosis

To the Editor: Dermatomyositis (DM) is an autoimmune disease associated with high rates of disability and mortality. It is characterized by distinct cutaneous rashes and muscle inflammation, with potential internal organ involvement.1 In addition to the classic DM-associated cutaneous manifestations, novel findings, such as seborrheic dermatitis–distributed rash, have been reported.2 We investigated the cutaneous manifestations of DM in large clinical samples and found that pseudoangioedema in DM is uncommon but clinically significant.

A severe case of Israeli spotted fever with pleural effusion in Italy

BackgroundThe most common Italian rickettsiosis is Mediterranean Spotted Fever (MSF). MSF is commonly associated with a symptom triad consisting of fever, cutaneous rash, and inoculation eschar. The rash is usually maculopapular but, especially in severe presentations, may be petechial. Other typical findings are arthromyalgia and headache. Herein, we describe for the first time an unusual case of Israeli spotted fever (ISF) associated with interstitial pneumonia and pleural effusion in which R. conorii subsp. israelensis was identified by molecular methods in the blood, as well as in the pleural fluid.Case presentationA 72-year-old male presented with a 10-day history of remittent fever. On admission, the patient’s general condition appeared poor with confusion and drowsiness; the first assessment revealed a temperature of 38.7°, blood pressure of 110/70 mmHg, a blood oxygen saturation level of 80% with rapid, frequent, and superficial breathing using accessory muscles (28 breaths per minute), and an arrhythmia with a heart rate of 90 beats per minute. qSOFA score was 3/3. Chest CT revealed ground-glass pneumonia with massive pleural effusion. Petechial exanthema was present diffusely, including on the palms and soles, and a very little eschar surrounded by a violaceous halo was noted on the dorsum of the right foot. Awaiting the results of blood cultures, broad-spectrum antibiotic therapy with meropenem 1 g q8h, ciprofloxacin 400 mg q12h, and doxycycline 100 mg q12h was initiated. Doxycycline was included in the therapy because of the presence of petechial rash and fever, making us consider a diagnosis of rickettsiosis. This suspicion was confirmed by the positivity of polymerase chain reaction on whole blood for R. conorii subsp. israelensis. Thoracentesis was performed to improve alveolar ventilation. R. conorii subsp. israelensis was again identified in the pleural fluid by PCR technique. On day 4 the clinical condition worsened. Blood exams showed values suggestive of secondary hemophagocytic lymphohistiocytosis; 4 out of 8 diagnostic criteria were present and empirical treatment with prednisone was started resulting in a gradual improvement in general condition.ConclusionsIsraeli spotted fever may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis.

Neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios in juvenile systemic lupus erythematosus: correlation with disease manifestations.

This retrospective study aimed to investigate the usefulness of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for organ involvement and disease activity in newly diagnosed juvenile systemic lupus erythematosus (jSLE). A total of 186 jSLE inpatients were included for analysis. All participants' clinical characteristics and laboratory data were obtained from medical records. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score scale was used to assess disease activity. Mann-Whitney U test and Kruskal-Wallis test were performed for non-parametric variables between the groups. Spearman rank correlation coefficient was used to analyze correlations between variables. The NLR was significantly higher in participants with serositis as compared those without serositis [2.72 (1.71-5.0) vs. 2.08 (1.42-3.15), P=0.038]. The PLR was significantly higher in participants manifesting symptoms of cutaneous rash [130.0 (92.6-235.0) vs. 112.0 (49.3-169.0), P=0.002], and arthritis [167.0 (106.0-243.0) vs. 106.0 (53.6-176.0), P<0.001], as compared to participants without such involvement. The PLR in participants with hematological involvement was significantly lower than in those without such involvement [111.0 (53.6-191.0) vs. 138.0 (107.0-185.0), P=0.016]. The PLR in participants with positive anti-Smith (anti-Sm) antibody was significantly higher than that in those with negative anti-Sm antibody [140.0 (91.6-228.0) vs. 114.0 (60.9-176.0), P=0.006]. The NLR showed positive correlations with serositis (r=0.153, P=0.037), complement C3 and C4 (r=0.152, P=0.038 and r=0.177, P=0.016, respectively). The PLR showed positive correlations with cutaneous rash (r=0.227, P=0.002), arthritis (r=0.290, P<0.001), anti-Sm antibodies (r=0.20, P=0.006) and erythrocyte sedimentation rate (ESR, r=0.159, P=0.03). Negative correlations were found between PLR and hematological involvement (r=-0.177, P=0.015). Both the NLR and PLR had correlations with serological indicators, and may predict organ involvement in jSLE, particularly cutaneous, arthritis, serositis, and haematological involvement.

Exanthematous Drug Eruption as a Side Effect of Teneligliptin.

Sir, Teneligliptin – a novel dipeptidyl peptidase-4 (DPP-4) inhibitor is a widely used medication for managing Type 2 diabetes mellitus as a single agent or as an add-on therapy with other oral antidiabetic agents (OADs). Teneligliptin is a cost-effective drug compared to other Gliptins and has a favourable adverse effect profile. There have been anecdotal reports of increased allergic events with the usage of various DPP-4 inhibitors.[1] This case report highlights one such case that we encountered when Teneligliptin use, in a known diabetic on Glimepiride and Metformin therapy, precipitated an exanthematous drug eruption. A 63-year-old gentleman presented with a history of Type 2 diabetes mellitus for the past 4 years along with hypertension and benign prostatic hypertrophy. He had been previously treated with a combination of Metformin 500 mg/Glimepiride 2 mg once a day along with Telmisartan 20 mg OD and Tamsulosin 0.4 mg OD for his other comorbidities. His body mass index was 25.51 kg/m2. Lab investigations revealed that his fasting plasma glucose was 189 mg/dL and his HbA1 C was 8.0%. Due to poor glycaemic control, the Endocrinologist added Tab. Teneligliptin 20 mg OD to his present oral antidiabetic regime. After starting Teneligliptin, he presented with an exanthematous rash which appeared a few hours after starting the medication. He did not take the tablet on the second day. He had rashes persisting on the second day and the third day. The dermatologist saw him and documented pruritic maculo-papular rashes on his trunk and limbs with erythema of the palms. There were no target lesions or oral lesions. Hence Teneligliptin was discontinued. He was given topical steroids (Betamethasone 0.1% w/w 20 g cream), white soft paraffin 13.2% and light liquid paraffin 10.2% 100 g cream for 7 days. The lesions disappeared gradually after discontinuation of the drug without leaving any residual skin lesions. Adverse drug reactions were assessed based on Naranjo Algorithm and it showed a score of 7 and this is a probable risk. Table 1 shows the application of the Naranjo scale for this particular patient.[2]Table 1: Naranjo nomogram as applied to this patientTeneligliptin is a widely used DPP-4 inhibitor in India due to its economic pricing and easy availability. Teneligliptin is not approved by the US food and drug administration. It is approved in Japan, Argentina, Korea, and India.[1] Most of the DPP-4 inhibitors have occasionally been reported to cause cutaneous reactions. In a study by Prabhat Agrawal et al.,[3] Teneligliptin induced diffuse erythematous pruritic cutaneous rash all over the limbs and trunk within 2 days after administration of the drug. Then the drug was stopped and Fexofenadine 120 mg once daily and topical emollients were started. The rash disappeared within 5–7 days and the symptoms reappeared when the drug was re-administered. Hence the drug was stopped in that particular person. Kaori Nakatani reported a Sitagliptin-induced drug eruption which occurred 6 months after initiation of the drug and gradually subsided after the cessation of Sitagliptin; except small itchy erythematous eruptions continued to appear due to photosensitive reaction of the drug. This is probably due to the structure and adsorption spectrum of Sitagliptin. It has three adsorptive peaks; both the 199.0 and 265.0 nm wavelengths are within the UV-C spectrum, while the 400.1 nm absorbance peak absorbs UV-A–visible light. Thus, Sitagliptin could cause persistent photosensitive eruption after cessation of the drug even with protection from UV light by hapten formation with subcutaneous protein.[4] The UV absorption spectrum of Teneligliptin is 244.80 nm.[5] Wavelengths within the UV-A (320–400 nm) and UV-B (290–320 nm) range are more likely to cause drug-induced photosensitivity reactions.[6] Here the patient presented with idiosyncratic delayed hypersensitivity pruritic exanthematous rashes and the dermatologist documented it as generalized pruritic maculo-papular rashes on the trunk and limbs with erythema of the palms. The lesions were not confined to sun-exposed areas and the mucosa was spared. CONCLUSION In the present case, generalized skin reactions appeared after the administration of Teneligliptin within a day and the symptoms disappeared after the cessation of the drug with anti-allergic treatment. Hence we suggest that the skin reaction observed in this case is Teneligliptin induced and close attention should be maintained for patients who are prescribed with Teneligliptin for any adverse cutaneous events. In addition, DPP-4 drugs are known to have photosensitive reactions, and hence this group of drugs should be administered cautiously in patients who are known to have photosensitive reactions with other medications. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Mycoplasma Pneumoniae-Induced Rash and Mucositis: A Systematic Review of the Literature.

INTRODUCTIONMycoplasma pneumoniae (MP) is a common respiratory pathogen that can result in community-acquired pneumonia (CAP). Approximately 25% of patients diagnosed with MP experience extrapulmonary manifestations. Mycoplasma-induced rash and mucositis (MIRM) was coined as a unique disease process in 2014. MIRM has prominent mucositis with or without a characteristic vesiculobullous and/or atypical targetoid eruption. Appropriate identification of this disease is important because it has a milder disease course with low rates of sequelae, and lower mortality compared to Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis. The objective of this systematic review was to examine the English literature on Mycoplasma Pneumonia-induced rash and mucositis since the establishment of its diagnosis in 2014.METHODSThe following online databases were used to identify appropriate studies that met the established inclusion and exclusion criteria: Pubmed, Cochrane, MedLine, Health Evidence, EPPI center, Allied Health Evidence. The following MesH search terms were used to further identify articles; “Mycoplasma pneumoniae induced rash and mucositis,” “Mycoplasma pneumoniae rash and mucositis,” “Mycoplasma pneumoniae rash,” “Mycoplasma pneumoniae mucositis,” “MIRM,” “Mycoplasma induced rash and mucositis,” “Mycoplasma rash and mucositis,” “Mycoplasma rash,” and “Mycoplasma mucositis.” Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.RESULTSOne hundred and seventy-five records were initially screened, and nineteen studies were included in the review, leading to a total of 27 patients. Patients had a mean age of 16 years old (Range 4 - 46 years old), with the majority being males (74%). Pulmonary symptoms tended to precede extrapulmonary symptoms on an average of 7.8 days. Extrapulmonary symptoms consisted of oral lesions (96.3%) followed by ocular lesions (92.6%) and genital lesions (59.3%). Female patients were more likely to have genital lesions (71.4%) when compared with male patients (55%). Cutaneous rashes occurred in approximately one-half of the patients, which supports the theory that MIRM is a separate clinical entity from SJS and other related skin disorders.Confirmatory testing for MIRM was performed using IgM/IgG Mycoplasma antibody testing or PCR in 19 (66.7%) and 6 (22.2%) patients respectively, although four cases reported the use of both serology and PCR, while five did not report confirmatory testing. Systemic antibiotics were used frequently in treatment 22 patients (77.8%) and 27 (100%) of the patients received various supportive care. Approximately 11 (37%) patients of reported cases used systemic steroids to reduce systemic inflammation. Other systemic treatments were used in six (21.4%) cases, and included intravenous immunoglobulins and cyclosporine A. Only eight patients (22.2%) reported having any lasting sequelae.CONCLUSIONMycoplasma-induced rash and mucositis is a recently described extra-pulmonary manifestation of Mycoplasma pneumoniae infections. To the best of the authors’ knowledge, this is the first systematic review of the MIRM literature since the introduction of the diagnosis in 2014. The authors hope that this review can serve to better our current understanding and lead to improved identification, work-up, and treatment of this disease. One notable limitation of this study is the relatively small sample size, which is due to the recent introduction of the term.

Immune-mediated adverse events in immune checkpoint inhibitors therapy: literature review

Immune-mediated adverse events (imAEs) are complications of therapy with immune checkpoint inhibitors, which arise as a result of autoimmune inflammation. The article summarizes systemic (fatigue, fever), cutaneous (rash, itching), gastrointestinal (diarrhea, colitis, hepatitis, pancreatic dysfunction), endocrinological (hypothyroidism, hypophysitis, adrenal insufficiency, diabetes mellitus), pulmonary (pneumonitis, pleuritis), rheumatological (arthralgia), neurological (headache, sensory and motor disorders), renal (acute interstitial nephritis, lupus-like nephritis, granulomatous nephritis, diffuse interstitial nephritis and minimal change disease), hematological (anemia, cytopenia), cardiovascular (myocarditis) and ocular (conjunctivitis, episcleritis, ceratitis, blepharitis and uveitis) imAE. Pathogenetic mechanisms and treatment approaches (in accordance with toxicity grade and clinical recommendations) are discussed. Early symptom recognition, patient education and timely intervention are crucial for imAE correction.