سلسلة الأمراض المحرضة بالأدوية

[dr.Hazem]

متلازمة الليمفوما الكاذبة المُحرضة دوائياً
Drug-Induced Pseudolymphoma Syndrome

أول الأدوية التي تُذكر تحت هذا العنوان هي مضادات الاختلاج Anticonvulsants، خصوصاً الفينيتوين phenytoin و الكاربامازبينcarbamazepine،
حيث أنهما يُسببان أغلب حالات الليمفوما الكاذبة drug-induced pseudolymphoma و فرط التحسس الدوائي drug-induced hypersensitivity syndrome .



وفيما يلي أسماء الأدوية التي تُسبب هذه الحالة مصنفة حسب مجموعاتها الدوائية:

- مضادات اضطراب النظم Antiarrhythmics :
Phenytoin, carbamazepine, butabarbital,
lamotrigine, mephenytoin, methsuximide,
phenobarbital, phensuximide, primidone,
trimethadione, ethosuximide, mexiletine, procainamide


- الصادات الحيوية Antibiotics :
Flucloxacillin,dapsone, cefixime, nitrofurantoin, penicillin, sulfonamides

- مانعات التجلطAnticoagulants : واحد فقط هو Fluindione

- مضادات الاكتئاب Antidepressants :
Amitriptyline, bupropion, desipramine, doxepin, fluoxetine, lithium, maprotiline

- مضادات الهستامين Antihistamines :

# من H1 blockers : وهو Diphenhydramine

# منH2 blockers : هما Cimetidine, ranitidine


- خافضات ضغط الدم Antihypertensives :

# Alpha agonists : وهو Clonidine

#مثبطات خميرة الانجيوتنسنACE inhibitors : وهي Benazepril, captopril, enalapril, lisinopril

#حاصرات مستقبلات الانجيوتنسن Angiotensin receptor blockers : اثنان Losartan, valsartan

# حاصرات بيتا Beta-blockers : اثنان هما Atenolol, labetalol

#حاصرات قنوات الكالسيوم Calcium channel blockers : وهما Diltiazem, verapamil

# المدرات Diuretics : وهيHydrochlorothiazide, hydrochlorothiazide with amiloride

# موسعات الأوعية الدموية Vasodilators : واحد فقط Hydralazine


- مضادات الذهان Antipsychotics :
Phenothiazines (chlorpromazine, thioridazine, promethazine)

- مضادات الرثية Antirheumatics :
Allopurinol, D-penicillamine, Gold, nonsteroidal anti-inflammatory drugs

- بنزوديازبين Benzodiazepines :
Clonazepam, lorazepam

- العلاجات الكيميائية Chemotherapeutics :
Cyclosporine, methotrexate, imatinib (Gleevec),
glatiramer acetate, oxaliplatin/5-fluorouracil/leucovorin


- المنبهات المركزيةCNS stimulants :
Methylphenidate hydrochloride

- HMG-CoA reductase inhibitors :
Lovastatin

- Mast cell stabilizers :
Cromolyn sodium

- الستيرويدات الجنسية Sex steroids :
Estrogen, progesterone

- الأدوية الموضعية Topical agents:
Etheric plant oil, menthol, hydroquinone cream

- اللقاحاتVaccines :
Hepatitis A or B vaccine injection sites

[nehad]

رائع ننتظر المزيد

[صيدولة]

موضوع ملفت كتير .... الله يعطيك العافية ... ناطرين التكملة ..

[dr.Hazem]

الله يعافيكم ..أكيد في مزيد...

[Dr.Ahmad]

الف شكر حازم موضوع مرجعي ممتاز ..

[Pharmakon]

جمييييييييييل .... موضوع مهم جدا ....وقت مادرسنا الجزء ده كان فيه شويه صعوبات وخصوصا انو اسماء الداويه كتيره ....لكنى كنت اسمتع بفهمو

موضوع مهم ودوك حازم الله عيطيك العافيه عرضو بشكل مميز لكن اطلب من طلب .... يتكلم شويه عن Pseudolymphoma Syndrome

[Dr.Ahmad]

دكتورة سارة هي المقالة من موقع emedicine.medscape.com عن سؤالك بتمنى تفيدك



Drug-Induced Pseudolymphoma Syndrome

Background

Drug-induced pseudolymphoma syndrome refers to a benign, drug-induced lymphocytic infiltrate in the skin that mimics cutaneous lymphoma histologically, clinically, or both. While the clinical presentation can be highly variable, typically patients present with the insidious development of an asymptomatic singular lesion (papule, nodule, or plaque) following weeks to months of a drug exposure. Less often, multiple lesions or widespread skin involvement (erythroderma) is seen. The skin lesions typically resolve within several months of withdrawal of the offending agent. and may recur with reinitiation of the implicated drug.

Since its initial report as a reaction to phenytoin more than 50 years ago, more than a dozen additional drugs have been implicated. Clinicians should consider this diagnosis in patients with the appropriate clinical presentation and a history of drug therapy with one or more of the implicated agents.

Drug-induced pseudolymphoma syndrome is a subtype of cutaneous pseudolymphoma , a heterogenous group of benign T- or B-cell cutaneous lymphoproliferative processes with histologic features of malignancy but benign clinical behavior.1 In most cases of cutaneous pseudolymphoma, the cause is unknown. When the cause is known, most experts suggest the inciting agent be stated in the diagnosis. Along with medications, other reported causes of cutaneous pseudolymphoma include photosensitivity, trauma, folliculitis, foreign agents (eg, tattoo dyes, insect bites, scabies, arthropod venom, vaccinations, hyposensitization injections, gold, acupuncture), and infections (eg, HIV, varicella-zoster virus, Borrelia burgdorferi).

Nomenclature

The heterogenous clinical, histological, and etiologic nature of cutaneous pseudolymphoma along with the association of drug-induced hypersensitivity reactions has resulted in many different classification schemes and potentially confusing nomenclature. The term drug-induced pseudolymphoma has been used to describe 2 kinds of adverse cutaneous drug reactions. The first is a subacute disease confined to the skin, which is the focus of this article. The second is an acute syndrome with a cutaneous eruption and associated systemic symptoms, also referred to as drug-induced hypersensitivity syndrome.

The confusion is furthered because the prototypic drug stimulus in both is phenytoin. Bocquet et al proposed the acronym DRESS (drug rash with eosinophilia and systemic symptoms) in 1996 to decrease the ambiguity of the term hypersensitivity syndrome. The hypersensitivity syndrome has been postulated to represent a distinct clinical entity with a distinct biologic mechanism; however, the significant clinical overlap (ie, implicated drugs, symptomatology, and presentation) and histologic overlap make the nosologic distinction of these entities difficult to resolve.


Pathophysiology

In contrast to classic drug eruptions, which develop minutes to days from drug ingestion and quickly resolve with drug discontinuation, the time course of drug-induced pseudolymphoma syndrome is prolonged and suggests a distinct biologic mechanism. Some postulate that drug-induced immunodysregulation results in the lymphoproliferative process. Abnormally functioning lymphocytes may proliferate in response to an antigen from the drug itself, an antigen unmasked by drug metabolism, or another nonpharmacologic antigen. Supporting this theory, alterations in immune function have been demonstrated in vivo or in vitro for many of the causative agents.

Usually, drug-induced cutaneous pseudolymphoma is a T-cell proliferation, but occasional B-cell–predominant forms have been reported. In general, evidence of T- or B-cell clonality (by polymerase chain reaction analysis of T-cell receptor or immunoglobulin H gene rearrangement or immunohistochemical light chain analysis) supports true lymphoma, whereas polyclonality supports a pseudolymphomatous proliferation; however, both polyclonal lymphomas and monoclonal pseudolymphomatous infiltrates have been well documented in the literature. Alone, clonality is insufficient to predict clinical behavior.

The emerging consensus is that pseudolymphomatous and lymphomatous proliferations represent 2 ends of a spectrum. Supporting this theory are examples of antigen-driven lymphoproliferation and progression to lymphoma in other organ systems (ie, Helicobacter pylori –related gastric mucosa-associated lymphoid tissue [MALT] lymphoma). Transformation of drug-induced cutaneous lymphocytic infiltrates to malignant lymphoma has been reported with phenytoin; however, many of these cases predate the availability of current diagnostic standards and may have represented cases that would now be classified as hypersensitivity syndrome.

Some authors believe the reported cases of transformation may actually have represented diagnostically challenging indolent B-cell cutaneous lymphomas. Similar cases involving pseudolymphomatous T-cell infiltrates progressing to true T-cell cutaneous lymphoma may potentially occur, but theses cases are less well-documented in the literature.

Individuals with a slow acetylator phenotype may be more susceptible to developing atypical lymphoid dyscrasias, owing to differences in drug metabolism kinetics, which may allow a pharmacologic antigen more opportunity to elicit an immune response or allow toxic drug metabolites to alter lymphocyte function. This proposed pathophysiology pertains primarily to drug-induced hypersensitivity syndrome. Thus, the details are not discussed extensively here; however, similar mechanisms of immunodysregulation have been suggested for drug-induced pseudolymphoma syndrome.


Frequency

United States

Although drug-induced pseudolymphoma remains a rare disorder, more than 100 individual cases have been reported in the literature worldwide.

Mortality/Morbidity

In most cases, drug-induced pseudolymphoma regresses spontaneously following withdrawal of the offending agent. Misdiagnosis of these lesions as a malignant entity could lead to inappropriate chemotherapeutic treatment.

Little is understood about the natural course of these lesions if drug exposure is allowed to continue. As discussed, transformation into malignant lymphoma has been reported in the literature, but many of these cases predate current diagnostic standards. Progression from a benign lymphocytic cutaneous infiltrate to cutaneous lymphoma remains poorly defined; however, close clinical follow up is prudent to monitor for such an event.

Mortality rates associated with drug-induced hypersensitivity syndrome can reach as high as 10%, and the condition requires specific therapy.


Race

No racial predilection is apparent for drug-induced pseudolymphoma syndrome. Drug-induced hypersensitivity syndromes may affect black patients more frequently than white patients. The familial aggregation seen may be due to inherited defects in drug metabolism, making some patients more susceptible.


Sex

Men and women are equally affected.

Age

In the largest published series, the average patient age was 61 years. Individual cases have been reported to range from childhood to the ninth decade of life.

Clinical

History

The onset of drug-induced pseudolymphoma is insidious. Most patients present with a single slowly enlarging papular, nodular, or plaquelike lesion several weeks following the initiation of implicated medications. However, several patients have demonstrated drug-induced pseudolymphoma after more than 5 years of therapy.

In the drug hypersensitivity syndrome, patients frequently report intermittent low-grade fever and local or diffuse lymphadenopathy. Constitutional symptoms may include headache, nausea, malaise, arthralgias, conjunctivitis, and pharyngitis.

Physical

Erythematous patches, similar to mycosis fungoides (MF), may be seen, but, in contrast to MF, they may be more localized and not restricted to sun-protected sites. Frequently, a small number of erythematous indurated papules, plaques, or nodules are seen. Rarely, a solitary tumor may appear.

In the drug hypersensitivity syndrome, the patients may present with features of Sézary syndrome. Other physical findings associated with the hypersensitivity syndrome include splenomegaly, marked localized or diffuse lymphadenopathy, and high-grade fever.

Causes

Anticonvulsants, typically phenytoin and carbamazepine, are the most frequent cause of drug-induced pseudolymphoma. Nevertheless, the number of implicated agents reported to cause either drug-induced pseudolymphoma or drug-induced hypersensitivity syndrome is expanding.


Drug classes and the reported subclasses and agents are as follows:


Antiarrhythmics - Phenytoin, carbamazepine, butabarbital, lamotrigine, mephenytoin, methsuximide, phenobarbital, phensuximide, primidone, trimethadione, ethosuximide,1 mexiletine, procainamide
Antibiotics - Flucloxacillin, dapsone, cefixime, nitrofurantoin, penicillin, sulfonamides
Anticoagulants - Fluindione
Antidepressants - Amitriptyline, bupropion, desipramine, doxepin, fluoxetine, lithium, maprotiline
Antihistamines
H1 blockers – Diphenhydramine
H2 blockers – Cimetidine, ranitidine
Antihypertensives
Alpha agonists – Clonidine patch
ACE inhibitors – Benazepril, captopril, enalapril, lisinopril
Angiotensin receptor blockers – Losartan, valsartan
Beta-blockers – Atenolol, labetalol
Calcium channel blockers – Diltiazem, verapamil
Diuretics – Hydrochlorothiazide, hydrochlorothiazide with amiloride
Vasodilators – Hydralazine
Antipsychotics - Phenothiazines (chlorpromazine, thioridazine, promethazine)
Antirheumatics - Allopurinol, D-penicillamine, Gold, nonsteroidal anti-inflammatory drugs
Benzodiazepines - Clonazepam, lorazepam
Chemotherapeutics - Cyclosporine, methotrexate, imatinib (Gleevec), glatiramer acetate, oxaliplatin/5-fluorouracil/leucovorin
CNS stimulants - Methylphenidate hydrochloride
HMG-CoA reductase inhibitors - Lovastatin
Mast cell stabilizers - Cromolyn sodium
Sex steroids - Estrogen, progesterone
Topical agents - Etheric plant oil, menthol, hydroquinone cream
Vaccines - Hepatitis A or B vaccine injection sites

[dr.Hazem]

تضخم اللثة الدوائي
Drug-Induced Gingival Hyperplasia

تضخم اللثة Gingival hyperplasia secondary to drugs ، أو فرط نمو اللثة الدوائي Gingival overgrowth ( أي الذي ينتج عن استعمال بعض أنواع الأدوية) اكتُشف للمرة الأولى عند بعض الأطفال الذين يستعملون الفنيتوين phenytoin لمعالجة حالات الصرع.

بعدها، لاحظ الأطباء أن استعمال نوع من الأدوية الكابتة للمناعة immunosuppressant وهو السيكلوسبورين cyclosporine ،، بالإضافة إلىبعض حاصرات قنوات الكالسيوم calcium channel blockers ( خصوصاً النيفيديبينnifedipine ) ،، يُصاحبها أيضاً تضخم في اللثة.


والسؤال، كيف تُسبب هذه الثلاثة تضخم اللثة؟؟

اقترح بعض الأطباء أن الفينيتوين والسيكلوسبورين و النفيديبين تسبب تضخم اللثة ( في الأفراد الذين تزيد احتمال اصاباتهم بها *) عن طريق تأثيرها على ثلاثة أشياء :
الخلايا الكيراتينية الظهارية epithelial keratinocytes،، و الأرومات اللمفية fibroblasts،، و الكولاجين collagen.

الفينيتوين phenytoin : يوقف عمل الأرومات اللمفية،،

السيكلوسبورين cyclosporine : يعيق الوظائف الأيضية للأرومات اللمفية( تصنيع الكولاجين وتكسيره)،،

أما النيفيديبين nifedipine : يقلل من تصنيع البروتين داخل الأرومات اللمفية.




*من هم الأفراد الأكثر استعداداً ( أو الأكثر قابلية) للإصابة بتضخم اللثة الدوائي؟؟

ليس بالضرورة أن يُصاب المريض الذي يستعمل الفينيتوين أو السيكلوسبورين بتضخم اللثة، فهنالك عوامل أخرى تؤثر في إحتمال الإصابة بها، هذه العوامل تشمل التالي:

- إهمال صحة الأسنان Oral Hygiene .

- الإصابة بأمراض في دواعم الأسنان Periodontal Disease.

- بحسب عمق جيبة دواعم السن Periodontal Pocket Depth.

- التهابات اللثة Gingival Inflammation.

- الإصابة باللويحات السنية Dental Plaque.

- جرعة ومدة استعمال السيكلوسبورين.

- استعمال السيكلوسبورين و النفيديبين معاً.

[nehad]

رائع شكرا د0حازم ننتظر المزيد

[صيدولة]

حلو كتير
بس كأنن صعبين ؟؟؟

مشكورين دكاترة... الله يعطيكن العافية ...
فعلا موضوع مرجعي ممتاز ...