Acquired Thrombotic Thrombocytopenic Purpura Following Inactivated COVID-19 Vaccines: Two Case Reports and a Short Literature Review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in December 2019, causing millions of deaths all over the world, and the lack of specific treatment for severe forms of coronavirus disease 2019 (COVID-19) have led to the development of vaccines in record time, increasing the risk of vaccine safety issues. Recently, several cases of thrombotic thrombocytopenic purpura (TTP) have been reported following COVID-19 vaccination. TTP is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia and ischemic end-organ lesions. It can be either congenital or acquired. Various events such as viral infections, medication, pregnancy, malignancies, and vaccinations may cause TTP. Here, we report two cases of acquired TTP following Sinopharm COVID-19 vaccine (BBIBP-CorV) and Sinovac COVID-19 vaccine (CoronaVac). Diagnosis was based on clinical presentation and confirmed with a severe reduction in the activity of von Willebrand factor-cleaving protease ADAMTS-13 and the presence of inhibitory autoantibodies. The two patients were successfully treated with corticosteroids, plasma exchange therapy and rituximab in the acute phase. In the literature, the reported cases of TTP induced by COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based COVID-19 vaccines. To the best of our knowledge, this is the first report of acquired TTP after inactivated virus COVID-19 vaccination.

Glutathione-S-transferase genetic polymorphism and risk of hepatotoxicity to antitubercular drugs in a North-African population: A case-control study.

INTRODUCTION: GST non-functional genotypes can lead to the accumulation of toxic intermediates, resulting in liver damage and increasing susceptibility to ATDH. AIM: To investigate the impact of GST Mu (GSTM1), GST Theta (GSTT1) null genotypes, and GST Pi (GSTP1; adenosine (A) > guanine (G), rs1695) variant allele on the development of ATDH in Tunisian patients treated with anti-tuberculosis therapy. METHODS: This was a case-control study including patients receiving anti-tuberculosis regimen. Cases (n = 23) were tuberculosis patients presenting ATDH during two months of anti-tuberculosis drug therapy. Controls (n = 30) were patients treated for tuberculosis, but presenting no ATDH. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No statistically significant association was observed between GSTM1 and GSTT1 homozygous null genotypes, and the risk of ATDH. A statistically significant association between GSTM1 and GSTT1 double null genotypes, and the risk of ATDH was found (p = 0.033) between cases and controls. For GSTP1, the distribution of GG homozygous mutant genotype was significantly associated with ATDH compared with the wild and the transition A to G (AA + AG) genotypes. CONCLUSION: Double deletion of GSTM1 and GSTT1 may predispose to ATDH in a Tunisian population. Moreover, GSTP1 rs1695 (A > G) genotyping can predict susceptibility to developing ATDH.

[Drug-induced vasculitis]. / Vascularites médicamenteuses : à propos d'une série de 13 cas.

INTRODUCTION: Drug-induced vasculitis is reported in almost 10-20 % of vasculitis. Several drugs may be incriminated in their occurrence. Our study aimed to study the epidemiological, clinical, histopathological and evolutionary characteristics of drug-indced vasculitis from a series of cases and to specify the different drugs involved. METHODS: We conducted a retrospective study during the period from January 2006 to December 2015 from the cases notified to the regional pharmacovigilance center of Sousse, Tunisia. The diagnosis was established according to the criteria proposed by the group of the American college of rheumatology (ACR). RESULTS: Our study included thirteen cases of drug-induced vasculitis over a ten-year period, with an mean incidence of 1.3 new cases per year. Mean age of patients was 40.84 years. The mean delay from the treatment onset was 14.46 days with extremes ranging from 5 days to six weeks. Most patients had pure skin involvement. Association with other extracutaneous complaints was present in five cases. Cutaneous biopsy was performed in all patients showing a pathological pattern of leukocytoclastic vasculitis, associated with fibrinoid necrosis, extravasation of red blood cells and allergic capillaritis. The outcome was favorable for all patients. The offending drugs in our series were amoxicillin, pristinamycin, rifampicin, fluconazole, metformin, glimepiride, phenobarbital, gabapentin, fenofibrate, ibuprofen, allopurinol, rituximab and tinzaparin. CONCLUSION: Anamnestic, clinical, biological and histopathological findings allow the early recognition of drug-induced vasculitis. Adequate treatment prevents systemic spreading and a worse prognosis.

A Rare Case of Azathioprine-Induced Sweet's Syndrome in a Patient with Crohn's Disease.

Sweet's syndrome has been reported in association with inflammatory diseases such as Crohn's disease. It has also been reported in association with several drugs. Here, we report a rare case of Sweet's syndrome induced by azathioprine in a patient with Crohn's disease.

Pustular drug hypersensitivity syndrome due to allopurinol.

Allopurinol hypersensitivity syndrome (AHS) is a severe drug reaction. It is characterized by rash, fever, and internal organ involvement. It may present in different clinical forms. We present a case of acute generalized exanthematous pustulosis occurring as a manifestation of AHS.

Paracetamol-induced Stevens Johnson syndrome and cholestatic hepatitis.

Stevens-Johnson syndrome (SJS) is an uncommon life-threatening skin disease, generally induced by drugs. Extracutaneous manifestations of the syndrome can occur, and may involve the conjunctiva, buccal mucosa, gastrointestinal and genitourinary tracts. Cholestatic hepatitis has been rarely described in SJS. A 29-year-old woman was admitted with generalized cutaneous eruption. A self-medication with paracetamol had been started three days earlier. Clinical signs and skin biopsy were consistent with SJS. Five days later, the patient developed jaundice. Serial liver function tests showed rising transaminases, bilirubin, alkaline phosphatase and γ-glutamyl transferase. Liver biopsy was performed and was consistent with the diagnosis of drug-induced cholestatic hepatitis. Adequate supportive care was provided to the patient. Skin lesions disappeared within two weeks. Jaundice disappeared progressively, and liver tests returned to normal. Herein, we report the first case of SJS associated with cholestatic hepatitis after ingestion of therapeutic doses of paracetamol.

Analysis of thiopurine S-methyltransferase phenotype-genotype in a Tunisian population with Crohn's disease.

This study was conducted to investigate the thiopurine S-methyltransferase TPMT activity distribution and gene mutations in Tunisian population with positive diagnostic for Crohn's disease. TPMT activity was measured in Tunisian population (n = 88) by a high performance liquid chromatography assay. Polymerase chain reaction-based methods were used to determine the frequency of TPMT mutant alleles TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. TPMT activity was normally distributed, ranging from 4.58 to 35.27 nmol/(h ml) RBC with a mean of 18.67 ± 7.10 nmol/(h ml) RBC. Seven TPMT*3A heterozygotes and one TPMT*3C homozygote were found in 88 patients, with allele frequencies of 0.039 and 1.13, respectively. TPMT*3A and the TPMT*3C, which cause the largest decrease in enzyme activity, were both variant alleles detected in the Tunisian population.

Insight into TPMT(∗)23 mutation mis-folding using molecular dynamics simulation and protein structure analysis.

Thiopurine S-methyltransferase (TPMT) is an important enzyme that metabolizes thiopurine drugs. This enzyme exhibits a large number of interindividual polymorphism. TPMT(∗)23 polymorphism has been reported in a few cases in the world in co-dominance with TPMT(∗)3A. The phenotype has been reported to affect enzyme activity in vivo and in vitro. Its underlying structural basis is not clarified yet. In our study, the wild type (WT) protein structure was analyzed and the amino acids bordering water channels in thiopurine sites were identified. Molecular dynamics of both the WT and TPMT(∗)23 mutation was carried out. In addition, the effects of this mutation, especially on the thiopurine site which is closed with a pincer like mechanism, were investigated. We focused on explaining how a locally occurred A167G substitution propagated through hydrogen bonds alteration to induce structural modification which affects both thiopurine and S-adenosylmethionine receptors. Finally, a genetic prediction of mutation functional consequences has been conducted confirming altered activity. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:20.

Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with positive rechallenge.

CONTEXT: Pancreatitis is a very rare adverse effect of tamoxifen with only six cases of tamoxifen-associated pancreatitis reported in the English literature until now. In these cases, rechallenge with tamoxifen was not carried out. CASE REPORT: We report a case of recurrent severe acute pancreatitis in a 44-year-old female induced by tamoxifen therapy and review the literature with regards to tamoxifen-associated pancreatitis. CONCLUSION: Clinicians should be aware of the risks of developing severe acute pancreatitis when using tamoxifen therapy. If tamoxifen is suspected as the probable causative agent, rechallenge with this drug should be prohibited.

Fatal allopurinol-induced hypersensitivity syndrome associated with pancreatic abnormalities.

Allopurinol hypersensitivity syndrome is a severe adverse reaction characterized by rash, fever, and internal organ involvement. We report a case of fatal allopurinol-induced hypersensitivity syndrome associated with acute pancreatitis.A 46-year-old man was treated by allopurinol for asymptomatic hyperuricemia. The patient developed a diffuse erythrodermic maculopapular eruption and fever. Laboratory analysis revealed cytolysis and cholestasis, amylases and lipases were highly elevated. Computed tomography scans revealed pancreatitis Grade C. The treatment of asymptomatic hyperuricemia should only be initiated when there is a clear indication to reduce the incidence and the severe consequences of allopurinol hypersensitivity syndrome.

Rare case of metformin-induced leukocytoclastic vasculitis.

OBJECTIVE: To report a case of leukocytoclastic vasculitis (LV) related to metformin. CASE SUMMARY: A 33-year-old woman developed palpable purpura on her lower limbs after starting self-medication with metformin 850 mg/day for weight loss. Drug-induced vasculitis was suspected, metformin was stopped, and the rash improved significantly. One month later, the woman again took metformin. Similar cutaneous lesions recurred, and skin biopsy showed LV, which was managed by discontinuing metformin and applying topical antiseptics. The patient had no further episodes of skin rash over a follow-up period of 3 months. DISCUSSION: Metformin has widespread use throughout the world. It has a variety of metabolic and vascular effects. Our patient developed a rash within a few days of metformin administration. Resolution of skin manifestations within several days after withdrawal of the drug and their recurrence when the drug was reintroduced were consistent with a pathogenic role of metformin. Other known causes of vasculitis were excluded in a reasonable way. According to the Naranjo probability scale, the vasculitis experienced by our patient was probably due to metformin. CONCLUSIONS: Clinicians should be aware of the ability of metformin to induce cutaneous LV.