Codeine phosphate-induced hypersensitivity syndrome

OBJECTIVE: To report a case of drug-induced hypersensitivity syndrome related to codeine phosphate. CASE SUMMARY: A 19-year-old Japanese man was prescribed codeine phosphate 10 mg 3 times daily and several other drugs for cold symptoms. About 20 days later, an erythematous, maculopapular rash appeared and progressed to erythroderma; a spiking fever also developed. He had splenomegaly and generalized lymphadenopathy on admission. Laboratory examinations showed atypical lymphocytosis, eosinophilia, and increased liver enzyme values. The platelet count slowly decreased after admission. The increased numbers of megakaryocytes in bone marrow and platelet-associated immunoglobulin (Ig) G antibodies in serum were compatible with a diagnosis of immune thrombocytopenic purpura. A significant increase in IgG antibodies to human herpesvirus 6 (HHV6) and transient viremia were helpful in diagnosing hypersensitivity syndrome. The results of patch tests were positive for codeine phosphate. An objective causality assessment revealed that an adverse drug event was probable. DISCUSSION: Codeine is an opioid analgesic. Severe adverse cutaneous reactions rarely occur. As of March 3, 2004, our case is, to our knowledge, the first report of hypersensitivity syndrome attributed to codeine phosphate. Drug-induced hypersensitivity syndrome is an acute, potentially life-threatening, idiosyncratic adverse reaction caused mainly by aromatic anticonvulsants. It is characterized by the triad of fever, skin rash, and internal organ involvement. Reactivation of HHV6 is involved in the pathogenesis of this syndrome and may have also caused the immune thrombocytopenic purpura in our patient. CONCLUSIONS: Codeine phosphate may rarely be associated with hypersensitivity syndrome. Clinicians should be aware that the potentially fatal syndrome can be caused by various drugs.     

Potential fluconazole-induced carbamazepine toxicity.

OBJECTIVE: To report a case of carbamazepine toxicity resulting from a drug interaction with fluconazole, and to review the possible mechanisms of this interaction. DATA SOURCES: Medical record review. DATA SYNTHESIS: A 33-year-old white man with a history of mental retardation and seizures experienced stupor due to carbamazepine toxicity after fluconazole was initiated. The patient had been taking carbamazepine for several years and maintained stable therapeutic concentrations. He started fluconazole therapy after developing a rash presumably due to candidiasis. After admission to the hospital for carbamazepine toxicity, both fluconazole and carbamazepine were withheld and the patient returned to his normal baseline mental status once the carbamazepine concentration declined to a therapeutic range. Carbamazepine was restarted and the patient experienced no further adverse events. Carbamazepine is metabolized by the cytochrome P450 3A4 isoenzyme. Fluconazole is renally excreted but has been noted to inhibit CYP3A4. Fluconazole has also been noted to increase phenytoin concentrations. CONCLUSIONS: Fluconazole may cause carbamazepine toxicity presumably by inhibiting the cytochrome P450 3A4 isoenzyme.     

Carbamazepine-induced pseudo mycosis fungoides

OBJECTIVE: To report a case of pseudo mycosis fungoides due to carbamazepine. CASE SUMMARY: A 54-year-old man experienced a skin lesion resembling mycosis fungoides without any systemic symptoms or signs 2 months after he had begun carbamazepine treatment for his seizures. Skin-punch biopsy specimens revealed mycosis fungoides-like histopathologic appearance. After drug discontinuation, the patient experienced complete remission of the clinical and pathologic findings. This suggests a diagnosis of pseudo mycosis fungoides due to carbamazepine. DISCUSSION: Mycosis fungoides is the cutaneous T-cell lymphoma of the skin that needs aggressive chemotherapy and radiation treatment. Pseudo mycosis fungoides is a condition caused by certain drugs that has a similar clinical and histopathologic appearance to mycosis fungoides. When the causative drug is discontinued, the lesions resolve completely. CONCLUSIONS: An objective causality assessment revealed that carbamazepine was highly probable as the cause of the adverse reaction. Patients who are diagnosed with mycosis fungoides should be asked about any drug use, and clinicians should recognize signs of pseudo mycosis fungoides.     

Hypersensitivity syndrome and pure red cell aplasia following allopurinol therapy in a patient with chronic kidney disease

OBJECTIVE: To report a rare case of combined hypersensitivity syndrome and pure red cell aplasia (PRCA) following allopurinol therapy. CASE SUMMARY: A 43-year-old woman with underlying mesangioproliferative glomerulonephritis developed fever, generalized morbilliform rash, leukocytosis with marked eosinophilia, and hepatic dysfunction 3 weeks after starting allopurinol therapy (300 mg/day for 3 days followed by 200 mg/day) for hyperuricemia and arthritis. The clinical findings were judged to be a probable drug reaction according to the Naranjo probability scale. The drug-induced hypersensitivity syndrome (DHS) resolved after withdrawal of allopurinol and initiation of systemic corticosteroid therapy. However, there was progressive worsening of anemia with reticulocytopenia; PRCA was suspected. PRCA was judged to be a possible drug reaction according to the Naranjo probability scale. The patient refused blood transfusion and bone marrow biopsy. Recombinant human erythropoietin was initiated in addition to prednisolone 15 mg daily. Eleven days later (approximately 7 wk after allopurinol withdrawal), both the hemoglobin level and reticulocyte count began to rise. The patient consented to a bone marrow study at that time, which confirmed the presence of dysplasia involving only the erythroid lineage. DISCUSSION: Allopurinol may induce DHS, aplastic anemia, and, in rare instances, PRCA. We report the first case of PRCA concurrent with allopurinol-induced DHS in a patient with chronic kidney disease. Discontinuation of allopurinol is the first step in the treatment of such cases. The slow recovery of PRCA might be partly attributed to her underlying chronic kidney disease. CONCLUSIONS: To minimize serious DHS, proper indications for treatment and dosage adjustment should be closely observed when starting allopurinol therapy in patients with chronic kidney disease.     

ACUTE PSYCHOSIS ASSOCIATED WITH ABRUPT WITHDRAWAL OF CARBAMAZEPINE FOLLOWING INTOXICATION

SUMMARY Carbamazepine is regularly used in the treatment of trigeminal neuralgia. Although exacerbation of psychosis has been described following abrupt discontinuation of carbamazepine in chronic schizophrenics, a withdrawal syndrome has not been reported previously in patients treated for trigeminal neuralgia. The case presented here suggests that abrupt withdrawal of toxic concentrations of carbamazepine may precipitate a withdrawal reaction, which is manifest some days after discontinuation of the drug. Therefore it may be advisable to withdraw therapy slowly in these situations.     

Successful infusion of 40 cryopreserved autologous bone-marrows. In vitro studies of the freezing procedure

Cryopreservation of human bone marrow may be helpful to use supralethal chemoradiotherapy in order to cure malignant diseases. We report here a cryopreservation procedure from large volumes of human bone marrow which can be applied in routinal use. Whole bone marrow in 10% Dimethylsulfoxide (ME2SO) was frozen at an 1 degree C/min. controlled rate and was stored into liquid nitrogen. After thawing and before infusion, both ME2SO and free hemoglobin were removed. The in vitro recovery of nucleated cells and the myeloid stem cell assay (CFC) were performed as quality control. About 60% of the marrow cells and 40% of the total CFC number were recovered at the end of the procedure. Using this technique, 40 patients (25 children with malignant lymphoma and 15 adults with lymphoma and solid tumors) were transplanted with autologous cryopreserved bone marrow after receiving intensive chemotherapy. Three of them received both chemotherapy and a total body irradiation. Engraftment was achieved in all patients. Rise in leucocyte count (greater than 1.10(9)/l) occurred within an average of 17 days. In conclusion, in autologous bone marrow transplantation, this method of cryopreservation is effective to obtain rapid hematological reconstitution in patients treated for malignant diseases by intensive cytoreductive regimens.     

Rash associated with piperacillin/tazobactam administration in infectious mononucleosis

OBJECTIVE: To report a case of piperacillin/tazobactam-induced rash in a patient with infectious mononucleosis. CASE SUMMARY: A 25-year-old white man developed a rash while receiving piperacillin/tazobactam 3.375 g intravenously every 6 hours and gentamicin for osteomyelitis complicating a left femur fracture secondary to a motorcycle accident. Due to progression of the rash following additional doses of piperacillin/tazobactam during hospitalization, the patient's antimicrobial regimen was changed to vancomycin and meropenem. Subsequently, a mononucleosis spot test was positive, and both Epstein-Barr virus (EBV) immunoglobulin (Ig) G and IgM antibodies were positive. The rash rapidly resolved with the discontinuation of piperacillin/tazobactam. DISCUSSION: Although the development of rash following the administration of several different antimicrobials, especially ampicillin, has been previously reported, this is the first report of piperacillin/tazobactam-induced rash in infectious mononucleosis. The rash is generally self-limiting and usually resolves within days of discontinuing the causative antimicrobial agent. An altered drug metabolism or an immune-mediated process has been suggested as the potential mechanism for rash development. CONCLUSIONS: Prior reports of antimicrobial-induced rash in infectious mononucleosis and a positive laboratory diagnosis of EBV in our patient with no history of penicillin allergy support the identification of piperacillin/tazobactam as the inducer of the rash. According to the Naranjo probability scale, the association of piperacillin/tazobactam with the rash was classified as probable.     

Carbamazepine-induced hyponatremia: assessment of risk factors

OBJECTIVE: To report a case of carbamazepine-induced acute hyponatremia resulting in seizures. CASE SUMMARY: A 44-year-old white woman developed acute hyponatremia and 2 subsequent tonic-clonic seizures after ingesting twice her evening dose of carbamazepine (usual evening dose 600 mg). On admission, her serum sodium level was 122 mEq/L. An infusion of NaCl 0.9% was begun and, within 24 hours, the serum sodium level had returned to her previous level of 136 mEq/L. The woman's preadmission carbamazepine concentration was 8.6 microg/mL, and it was 11.3 micorg/mL on admission. Carbamazepine was withheld and, the following day, the concentration was 5.6 microg/mL. The woman had experienced a similar event 6 months earlier when she also took a large dose of carbamazepine. DISCUSSION: We attributed the acute hyponatremia and seizures to the large increase in dose of carbamazepine in the presence of other risk factors for hyponatremia. Hyponatremia associated with carbamazepine has been well described. The incidence ranges from 1.8% to 40% depending on the patient population studied. Severe hyponatremia in patients treated with monotherapy is uncommon. Several risk factors have been reported to increase the risk of hyponatremia including age >40 years, concomitant use of medications associated with hyponatremia, menstruation, psychiatric condition, surgery, psychogenic polydipsia, and female gender. Treatment is focused on removal of the precipitating factors or discontinuation of carbamazepine therapy. Use of the Naranjo probability scale indicated a highly probable relationship between acute hyponatremia and carbamazepine in our patient. CONCLUSIONS: Hyponatremia with carbamazepine is well known. The factors associated with increased risk are less understood. An increased awareness of these risks, careful monitoring, and patient education are important in the prevention of neurologic complications.     

A case of SUNCT syndrome responsive to zonisamide

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare headache syndrome that represents a subtype of trigeminal autonomic cephalalgia thought to be highly refractory to treatment. More recently, numerous anticonvulsant agents including lamotrigine, topiramate, gabapentin, and carbamazepine have been reported to be partially or completely effective for treating SUNCT. We report the case of a patient with SUNCT in whom symptoms were completely relieved with carbamazepine at 600?mg/day. However, carbamazepine had to be discontinued due to severe rash. Zonisamide was selected for continued treatment, as a Na-channel blocker like carbamazepine but with lower risk of producing skin rashes as caused by carbamazepine. Attacks ceased completely with 300?mg/day of zonisamide achieving a blood serum level of 19?μg/ml. This is the first case report to describe zonisamide alone completely eliminating SUNCT symptoms. Zonisamide should be considered a viable candidate drug for the treatment of SUNCT.     

Prevention of parvovirus B19-induced repetitive acute kidney failure by subcutaneous immunoglobulins

Human parvovirus B19 has been associated with various cases of kidney injuries with different glomerular phenotypes. In immunocompromised individuals, insufficient production of neutralizing antibodies can lead to chronic PVB19 carriage and manifestations. However, PVB19 DNA has been detected in bone marrow and peripheral blood for months or years in seemingly immunocompetent individuals, despite the presence of neutralizing antibodies. We report here PVB19-induced recurrent anuric acute kidney failures in a 57-year-old man over a 7-year period with persistent PVB19 infection and then PVB19-associated cryoglobulinemia. Acute renal failures were preceded by influenza-like syndrome associated with arthralgia, skin rash, and low-grade fever. Serum, bone marrow, renal, and digestive PVB19 replication was found in the different episodes. Endocapillary proliferative glomerulonephritis evolved into membranoproliferative glomerulonephritis. Complete renal recovery occurred after each bout. Off-label subcutaneous immunoglobulin therapy resulted in disappearance of blood and bone marrow PVB19 viral load and stopped the glomerulonephritis recurrence. Subcutaneous immunoglobulin therapy withdrawal resulted in renal relapse with cryoglobulin-associated manifestations.     

Nonthrombocytopenic purpura associated sequentially with nifedipine and diltiazem.

OBJECTIVE: To report the case of a patient who developed nonthrombocytopenic purpura sequentially following the administration of nifedipine and diltiazem. DATA SOURCES: Case reports, MEDLINE review of pertinent literature, and review of relevant studies. DATA EXTRACTION: Data were extracted from direct patient observation and review of laboratory studies and published reports. DATA SYNTHESIS: Nonthrombocytopenic purpura secondary to cutaneous vasculitis is a known, although rare, adverse effect of nifedipine. It has not been reported in association with diltiazem. We report the case of a 75-year-old woman in whom a purpuric rash demonstrated by biopsy to be attributable to cutaneous vasculitis developed in the course of nifedipine therapy. The rash disappeared after discontinuation of the drug; however, it recurred when diltiazem therapy was initiated. CONCLUSIONS: Nonthrombocytopenic purpura may be associated with diltiazem as well as with nifedipine. When this adverse effect occurs following administration of a calcium-channel blocker, caution is advised in using other agents of the same class.     

Severe linezolid-induced lactic acidosis in a child with acute lymphoblastic leukemia: A case report

Linezolid is an antibiotic increasingly used for treatment of resistant Gram-positive infections, which blocks bacterial proteosythesis through direct inhibition of mitochondrial ribosomes. The most common adverse effects of linezolid include gastrointestinal symtoms, peripheral neuropathy, bone marrow depression and lactic acidosis.Here we present a rare case of a 9-year-old female, a survivor of acute lymphoblastic leukemia (ALL) and a hematopoietic stem cell transplant (HSCT), who developed life-threatening lactic acidosis with vomiting, impaired consciousness and Kussmaul breathing after 51 days of intravenous linezolid administration due to mycobacterial infection. She fully recovered after drug discontinuation and normalization of the plasma levels.We conclude that plasma lactate concentrations should be monitored closely during any linezolid treatment, particularly in patients with hepatic or renal dysfunction.     

Possible trimethoprim/sulfamethoxazole-induced aseptic meningitis

OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced aseptic meningitis. CASE SUMMARY: An 18-year-old woman diagnosed with acute myeloid leukemia was admitted for a bone marrow transplant. She had already attained remission with daunorubicin, thioguanine, and high-dose cytarabine. A routine lumbar puncture performed on admission revealed an abnormally elevated leukocyte count, and meningitis was suspected. The patient had been taking TMP/SMX (trimethoprim 120 mg) twice daily on Monday, Tuesday, and Wednesday for the past 3 months; no other medication was being used. Upon examination, the patient mentioned having had headaches for the past few weeks. Since viral, bacterial, and fungal cultures were negative, a diagnosis of aseptic meningitis was made. According to the Naranjo probability scale, TMP/SMX was a possible cause of the aseptic meningitis. Eleven days after discontinuation of TMP/SMX, lumbar puncture results had returned to normal. DISCUSSION: Many drugs have been associated with aseptic meningitis. Antibiotics are often linked with aseptic meningitis, with TMP/SMX being the most frequently associated antibiotic. Many cases of TMP/SMX-induced aseptic meningitis have been reported, while few cases have been reported with trimethoprim and sulfamethoxazole given separately. CONCLUSIONS: Despite the widespread use of TMP/SMX and the years of experience we have had with the drug, it is important to remain vigilant regarding possible adverse effects, particularly aseptic meningitis.     

非霍奇金淋巴瘤患者骨髓细胞见棒状小体一例

目的 探讨一例非霍奇金淋巴瘤患者骨髓涂片中浆细胞出现类Auer小体的机制及意义。方法 患者骨髓穿刺涂片,瑞姬氏染色,观察细胞形态。回顾患者治疗过程。结果 该患者骨髓涂片中,除有少量淋巴瘤细胞外,部分浆细胞可见明显棒状小体。结论 浆细胞棒状小体出现,可能与放、化疗治疗相关。     

Pure red cell aplasia accompanied by COVID-19 successfully treated using cyclosporine

A 67-year-old Japanese man was admitted to our hospital with severe coronavirus disease 2019 (COVID-19) in March 2020. Mechanical ventilation was initiated 8 days after admission, due to severe respiratory failure. Multiple severe complications such as liver dysfunction, arrhythmia, brain infarction, and venous thromboembolism were also observed. We initially diagnosed Coombs test-positive warm autoimmune hemolytic anemia. Corticosteroids proved ineffective and anemia worsened with severe erythroid hypoplasia (0.5% erythroblasts in bone marrow), so we diagnosed pure red cell aplasia (PRCA). We also identified massive infiltration of cytotoxic T-lymphocytes expressing CD8, granzyme B, and perforin in bone marrow. Systemic cyclosporine was started, with full resolution of anemia and no need for blood transfusions after 4 weeks. We believe that this represents the first report of COVID-19-associated PRCA successfully treated using cyclosporine.     

Hepatotoxicity after short-term trazodone therapy.

OBJECTIVE: To report a case of severe hepatotoxicity from a four-day course of trazodone in a patient being treated according to protocol in a detoxification center. CASE SUMMARY: A 46-year-old HIV-positive man with a past medical history of intravenous drug abuse and hepatitis C, who was well controlled with HIV medications, was admitted for cocaine withdrawal. The patient was started on a standard protocol at the detoxification center with methadone 50 mg/d, clonidine 0.1 mg twice daily for four days, and trazodone 200 mg/d for four days. Laboratory results showed acute hepatitis and cholestasis five days following admission. Trazodone and clonidine were discontinued at that time. His methadone and HIV regimens remained unchanged. Liver function test results were greatly improved 10 days after trazodone and clonidine discontinuation. DISCUSSION: This is the first case report of trazodone-induced liver damage after only a few days of therapy. Previous reports describe hepatitis developing after weeks to months of trazodone therapy. All comorbidities thought to affect the described laboratory abnormalities were ruled out as a cause by a hepatologist. The observation of the sudden rise and fall of liver enzymes is characteristic of a drug reaction in the absence of trauma and severe shock. CONCLUSIONS: Due to the temporal relationship of the introduction and withdrawal of trazodone in the medication regimen and the elevations in liver enzymes, we conclude that this patient experienced acute hepatitis induced by trazodone 200 mg/d therapy for four days. The findings of this case warrant caution and closer monitoring in a patient with multiple risk factors for liver damage.     

Hemophagocytic lymphohistiocytosis secondary to composite lymphoma: Two case reports

BACKGROUNDHemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disease caused by inherited pathogenic mutations and acquired dysregulations of the immune system. Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphomas that occur in a single patient. Here, we report two cases of HLH secondary to composite lymphoma with mixed lineage features of T- and B-cell marker expression both in the bone marrow and lymph nodes in adult patients.CASE SUMMARYTwo patients were diagnosed with HLH based on the occurrence of fever, pancytopenia, lymphadenopathy, splenomegaly, hemophagocytosis and hyperferritinemia. Immunohistochemical staining of the axillary lymph node and bone marrow in case 1 showed typical features of combined B-cell and T-cell lymphoma. In addition, a lymph node gene study revealed rearrangement of the T-cell receptor chain and the immunoglobulin gene. Morphology and immunohistochemistry studies of a lymph node biopsy in case 2 showed typical features of T cell lymphoma, but immunophenotyping by flow cytometry analysis of bone marrow aspirate showed B cell lymphoma involvement. The patients were treated with high-dose methylprednisolone combined with etoposide to control aggressive HLH progression. The patients also received immunochemotherapy with the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen immediately after diagnosis. Both patients presented with highly aggressive lymphoma, and died of severe infection or uncontrolled HLH.CONCLUSIONWe present two rare cases with overwhelming hemophagocytosis along with composite T- and B-cell lymphoma, which posed a diagnostic dilemma. HLH caused by composite lymphoma was characterized by poor clinical outcomes.     

Lithium intoxication due to carbamazepine-induced renal failure

OBJECTIVE: To report the case of a patient with manic-depressive disorder who developed lithium intoxcation following carbamazepine-induced acute renal failure. CASE SUMMARY: A 33-year-old white man with bipolar manic-depressive disorder was treated with lithium for the last 18 months. Three weeks prior to admission, carbamazepine 600 mg was added to the drug regimen due to a recurrence of the psychiatric disorder. He was admitted wh signs of lithium intoxication. Acute renal failure due to carbamazepine-induced interstitial nephritis was diagnosed. DISCUSSION: The combination of carbamazepine and lithium is known to cause neurotoxicity. We describe a different interaction in which the toxic lithium concentrations were the result of carbamazepine-induced acute renal failure. CONCLUSIONS: When considering adding carbamazepine to lithium, careful follow-up of the patients is warranted to prevent this indirect drug in interaction.     

A strange lupus‐like malar rash with renal involvement: an angioimmunoblastic T‐cell lymphoma – A case report

Cutaneous malar rash and kidney involvement has not previously been reported as presenting symptoms of an angioimmunoblastic T‐cell lymphoma (AITL). We report a case of a woman with erythematous rash. A PET‐CT revealed a lymphadenopathy and splenomegaly. An inguinal lymph node biopsy showed an AITL. There was clinical improvement after prednisone.     

Cluster-tic syndrome

A case of cluster-tic syndrome is presented. A 51-year-old man developed pain attacks corresponding to the second branch of the trigeminal nerve. After treatment with 1200 mg carbamazepine daily, the attacks disappeared. Full remission was achieved, and carbamazepine therapy was continued. Pain attacks of a quite different character then appeared; their clinical picture corresponded to cluster headache. After treatment with cyproheptadine, the cluster headache attacks ceased, but 2 days later, before the discontinuation of the treatment, the attacks of trigeminal neuralgia reappeared. Treatment with carbamazepine was started again, and there was remission of the trigeminal neuralgia after several weeks.