CLL Complications

Prescription Drug Induced Complications

Date: July 12, 2003

by Chaya Venkat

Side Effects and Drug Interactions May Ruin Your Strategy

One of our members wrote about the possibility of response to foreign matter such as silicone particles from implants causing lymph node enlargement, high WBC, and other abnormalities in blood CBC mimicking lymphoma / leukemia. In other words, it looks like lymphoma, feels like lymphoma, but it is NOT lymphoma. It could be, as described in the abstract below, due to inflammatory response to a foreign particles. The second abstract addresses skin conditions caused by prescription drugs.

Abstracts:

J Clin Pathol. 2000 Jul;53(7):549-51.

Silicone lymphadenopathy mimicking a lymphoma in a patient with a metatarsophalangeal joint prosthesis.

Peoc'h M, Duprez D, Grice G, Fabre-Bocquentin B, Gressin R, Pasquier B. 

Department of Pathology, Centre Hospitalier Universitaire, Grenoble, France. 

With lymph node enlargement, the possibility of a malignant process such as metastatic carcinoma or lymphoma needs to be excluded. This report describes a 47 year old woman with inguinal lymph node enlargement initially suspicious for lymphoma. Fine needle aspiration findings favoured reactive hyperplasia, but a malignant process could not be excluded. The final histological diagnosis was a foreign body granulomatous inflammatory response as a result of regionally disseminated silicone particles from an over looked metatarsophalangeal joint prosthesis. Because of the large number of joint prostheses world wide, it should be kept in mind that migration of wear particles can create granulomatous inflammation and node enlargement. 

PMID: 10961180
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Arch Intern Med. 1989 Apr;149(4):829-32.

Cutaneous adverse reactions associated with calcium channel blockers.

Stern R, Khalsa JH.

Department of Dermatology, Beth Israel Hospital, Harvard Medical School, Boston, MA

The calcium channel blockers, nifedipine, verapamil, and diltiazem, are widely used for the treatment of cardiovascular disease. In spite of their widespread use, little data about the frequency and spectrum of cutaneous reactions associated with these agents have been published. Based on reports provided to the FDA's Division of Epidemiology and Drug Surveillance, and the American Academy of Dermatology's Adverse Drug Reaction Reporting System, it appears that the frequency of adverse cutaneous events associated with these drugs is low, but that occasionally severe reactions are associated with the use of these drugs. Among the more serious reactions associated with the calcium channel blockers are toxic epidermal necrolysis with diltiazem, Stevens-Johnson syndrome and erythema multiforme, which have been associated with all three drugs in this class, and exfoliative dermatitis, which has also been reported with all three agents. Most serious reactions associated with these agents occur within two weeks of initiating drug therapy. These findings suggest that calcium channel blockers are occasional causes of a wide spectrum of cutaneous reactions and should be considered as possible causative factors in patients who develop adverse cutaneous reactions while using these drugs. 

PMID: 2523214 
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Am J Clin Dermatol. 2003;4(6):407-28.

Progress in the understanding of the pathology and pathogenesis of cutaneous drug eruptions : implications for management.

Crowson AN, Brown TJ, Magro CM.

University of Oklahoma and Regional Medical Laboratories, Tulsa, OK

Cutaneous drug eruptions are among the most common adverse reactions to drug therapy. The etiology may reflect immunologic or nonimmunologic mechanisms, the former encompassing all of the classic Gell and Combs immune mechanisms. Cumulative and synergistic effects of drugs include those interactions of pharmacokinetic and pharmacodynamic factors reflecting the alteration by one drug of the effective serum concentration of another and the functions of drugs and their metabolites that interact to evoke cutaneous and systemic adverse reactions. Recent observations include the role of concurrent infection with lymphotropic viruses and drug effects that, through the enhancement of lymphoid blast transformation and/or lymphocyte survival and the contribution of intercurrent systemic connective tissue disease syndromes, promote enhanced lymphocyte longevity and the acquisition of progressively broadening autoantibody specificities. The latter are particularly opposite to drug-induced lupus erythematosus and to drug reactions in the setting of HIV infection. Specific common types of cutaneous drug eruptions will be discussed in this review. Successful management of cutaneous drug eruptions relies upon the prompt discontinuation of the causative medication; most drug eruptions have a good prognosis after this is accomplished. Oral or topical corticosteroids can be administered to aid in the resolution of some types of eruptions. Antihistamines or anti-inflammatory agents may also be administered for some eruptions.

PMID: 12762833
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Drugs Implicated in Dermatitis

A member asked if "exfoliative dermatitis" necessarily has a peeling effect and if a connection has ever been found between allergy medicines and dermatitis. 

I do not believe dermatitis problems arising out of drug-induced over reaction of the immune system is limited to a peeling effect of the skin. There seem to be many different ways in which these problems can be manifested. Below is a link to an excellent paper that lists some of the many drugs that can cause severe skin reactions, severe enough that they can be mistaken for cutaneous lymphoma, and severe enough that left untreated they may evolve into true malignancy. I have reproduced the drug list in Table-2 of this paper, for your reference. 

For those of you interested in the why and the mechanisms of things: apparently, drugs like calcium channel blockers (high blood pressure medication) work partly by increased blood flow to the peripheral regions of the body, namely the feet and hands. This way blood pressure is reduced elsewhere in the body. All that extra blood flow means skin cells can grow and flourish. In normal people with well balanced immune systems, the growth and proliferation of skin cells is matched by the rate at which they are shed as dead skin flakes. In some people, this process does not work well, and goes out of balance. Too many skin cells accumulate, the skin thickens and cracks and begins to peel. One of the major issues with this for CLL patients is that the skin is our primary defense against infections. Cuts, cracks and ruptures in the skin of the hands and feet is a huge window of vulnerability, an easy entry point for various infections. Even if you do not have serious dermal problems, it is important to keep your skin well looked after, soft and supple with moisturizers. So quit being macho, you guys, rough hands with cuts and nicks is not a good thing in combination with immune dysfunction. 

I am no expert on dermatology, just the little bit I have learned in the last few months trying to take care of P.C. One thing I can say with confidence, you will ignore dermal problems in combination with CLL at your own peril. Unfortunately, as we found out, there seem to be few dermatologists who are also competent oncologists. If you go to a multi-specialty cancer center, ask your primary oncologist to refer you to one of their dermatological oncologists, some one who specializes in this stuff. 

Article:

Article from American Family Physician (free full-text online version)

Drugs Associated with Erythroderma

Gulizz Karakayli, M.D., Grant Beckham, M.D., Ida Orengo, M.D., and Ted Rosen, M.D.

Baylor College of Medicine, Houston, TX

Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Although the etiology is often unknown, exfoliative dermatitis may be the result of a drug reaction or an underlying malignancy. The approach to treatment should include discontinuation of any potentially causative medications and a search for any underlying malignancy. One of the most common malignancies associated with exfoliative dermatitis is cutaneous T-cell lymphoma, which may not manifest for months or even years after the onset of the skin condition. Hospitalization is usually necessary for initial evaluation and treatment. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. The prognosis of cases associated with malignancy typically depends on the outcome of the underlying malignancy.

Drug List

Atlas of Dermal Conditions

They say a picture is worth a thousand words. Here is a terrific site that has a searchable database of pictures of the various kinds skin problems. I must warn you ahead of time, the pictures are pretty gory and frightening. Not for the faint of heart. They seem to present patients in advanced stages in each case. 

You can search the database by entering key words. For example, if you are interested in the palms of your hands cracking and peeling, enter the word "palms", then look through the pictures. It also provides literature references to read more about the topics that interest you. 

Here is the link: Dermatology Image Atlas from Dermatlas.org.

As I said, this is strictly PG13 stuff.

Drugs Implicated in Gum Problems

Here is more than you ever wanted to know, I am sure, about drug induced hyperplasia. In this case, "gingival hyperplasia". Just fancy words, gingival means gums, and hyperplasia means cells growing too fast, too many of them and they accumulate over time. 

Yesterday there was a post on ACOR about a patient with gingival overgrowth. This can show up as a lump on your gums that was not there before. Guess what, this, too, could be due to one or a combination of the prescription medications you might be taking. As described in the abstract below, the calcium channel blocker accumulates selectively in the gum tissue. When this is made worse by inflammation caused by bacterial plaque, it can get out of control very quickly. Two precautions to take: meticulous dental hygiene, and a review of your list of standard, maintenance medications. Many times the problem can be resolved by good dental care and gradually by discontinuing the drug that is causing the problem, switching to another that would do the same job, reducing the dosage, etc. 

Abstract:

J Fam Pract. 1994 Nov;39(5):483-8. 

Calcium channel blocker-induced gingival hyperplasia: case report and review of this iatrogenic disease. 

Lawrence DB, Weart CW, Laro JJ, Neville BW. 

Department of Family Medicine, College of Dental Medicine, Medical University of South Carolina, Charleston, SC.

Gingival hyperplasia is a common disorder associated with phenytoin and cyclosporine therapy. However, induction of this condition by calcium channel blockers is less well known. Inflammation of the gingival tissue from bacterial plaque and the subsequent development of gingival crevicular fluid may allow sequestration of the calcium channel blocker, thus predisposing the tissue to a localized toxic effect and the development of gingival hyperplasia. Calcium channel blockers have cellular effects similar to those of phenytoin and cyclosporine, including the production of a localized folic acid deficiency. All of the available calcium channel blockers have been reported to cause gingival hyperplasia. Treatment options include meticulous plaque control, and in severe cases, gingivectomy. Gingival hyperplasia can be prevented with meticulous plaque control or avoidance of the offending medication. 

PMID: 7964547
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