Lyme Disease Education and Support Groups of America

AfterTheBite@gmail.com

Contact: Lucy Barnes

PART I- This challenge is to The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America, (2006) “acrodermatitis chronica atrophicans” section, page 1113. (Photographs- Part II- separate document)

The Guidelines state: “Available data indicate that acrodermatitis chronica atrophicans may be treated with a 21-day course of the same antibiotics (doxycycline [B-II], amoxicillin [B-II], or cefuroxime axetil [B-III]) used to treat patients with erythema migrans (tables 2 and 3).”

The Guidelines recommend providing patients with the same three-week course of antibiotics for the early stages of Lyme disease as they do for the late, disseminated, multi-system, complex stages presenting years after the original treatment failed.

If recommended treatment had originally been successful, the later stages of Lyme disease would not be of concern, retreatment would not be necessary and people would not be suffering from what the Guidelines describe in their ‘acrodermatitis chronica atrophicans’(ACA) section as “insidious” multiple subjective and objective symptoms.

Throughout the Guidelines, the author’s mention they have limited or no experience treating people with various stages or presentations of the disease.

That one admission should have been the first clue that the authors were not qualified to make recommendations for or against any specific diagnostic or treatment protocol.

At the very least, the panel should have encouraged input from treating physicians in order to provide the most successful treatment options for patients. Had the panel intended for physicians to use clinical judgment, the gathering and use of all available data would have been incorporated in the Guidelines and fact gathering would have been a priority.

Instead, the IDSA panel rejected outside science and opinions from experts with hands-on experience. They compounded the problem by ignoring physician and patient feedback, even while aware of the growing number of treatment failures occurring nationwide by those following their Guideline protocols.

As a result of their failure to be flexible, both in their thinking and their recommendations, people have been misled, misdiagnosed and under treated for active Borrelia infections for years. While patient’s health crumbled, they were provided no treatment options via the IDSA Guidelines.

It was irresponsible for IDSA authors to take on the responsibility for developing Guidelines for medical conditions they do not understand, refused to review with those having knowledge of the condition and for which they have no experience in treating.

The authors should have refrained from making recommendations against treating patients who remain ill after a short course of antibiotics failed.

The IDSA’s attempt to set medical standards for the Lyme community, define illness and recommend treatment protocols have been nothing more than a hindrance to clinical judgment and patient autonomy. The Guidelines mere existence continues to fuel a war where the casualties are human lives.

With so many lives at stake, it is unconscionable to think the IDSA Guidelines would be so restrictive that people would be forced to wait for a later stage of the disease, specifically objective symptoms, to present (in this case the chronic ACA stages) and hope at that point they could receive treatment that might provide relief or at the least, give them a fighting chance to fend off future complications.

If the newly appointed review panel would substitute the word “cancer” for “Lyme” while reading the Guidelines, especially in regards to the ACA presentation, the point of this challenge would become crystal clear.

For example, partially treating cancer in the early stages, then withholding treatment until the more advanced stages are reached, then recommending the same unsuccessful treatment as what was already prescribed is not only ludicrous, it is an inhumane practice that is not acceptable by any standards, for any disease.

Although not listed in the IDSA Guidelines, the objective and subjective symptoms noted in patients with ACA are endless and well documented. There is no dispute in the medical community that these symptoms arise as a result of inadequately treated Borrelia infection.

Live, viable spirochetes have been extracted from ACA lesions from patients never treated originally and also those treated with what was thought to be “adequate treatment”. Many patients have suffered for years- between the original treatment prescribed and the eventual presentation of ACA- developing multiple complex and hard to treat symptoms, as the organisms spread throughout their body.

Complications associated with the final stages of ACA presentation, such as the difficult-to-treat ulcerations of atrophic skin, which can develop after minor trauma, give rise to the ACA stage being an especially traumatic one for patients.

Once at this stage, patient’s lives have often been compromised for years, sometimes for decades and often permanent damage has been done to one or more organ systems that will not subside and cannot be reversed.

Physicians and patients, by way of the IDSA Guidelines, should be offered a detailed description of the true and full presentation of ACA in order that informed decisions concerning treatment can be decided.

Had the panel authors intended clinical judgment and patient autonomy to be exercised for any stage of Lyme disease treatment, they would have disclosed scientific findings concerning the ACA presentation, however, this information was not provided.

Instead, the ACA section appears to have been thrown together in a haphazard fashion, devoid of detail and using little to no science for which to base the author’s recommendations. In addition, and more importantly, treatment for the ACA presentation is identical to treatment recommended for the early stages of Lyme disease, which failed to bring resolution or the promised cure.

The very existence of acrodermatitis chronica atrophicans lesions in patients shoots down the “post-Lyme syndrome” theory completely. ACA only develops in patients improperly treated for early Lyme disease years after they were infected (even after they were prescribed what is considered by the authors to be “adequate treatment”).

If continuing symptoms after treatment were due to anything other than active infection, the ACA would not appear, viable spirochetes would not be detected in the ACA lesions years after the initial Lyme infection and antibiotics would not be affective in clearing some of the symptoms associated with ACA.

This begs the following question and is worth repeating- For patients experiencing ongoing subjective symptoms after the IDSA recommended treatment for Lyme disease- how do they develop the ACA presentation if they have ”post-Lyme syndrome”? Keep in mind the authors’ contention is “post-Lyme syndrome” is not caused by active infection.

Those who develop ACA have the same symptoms that are listed as inclusion criteria for “post-Lyme syndrome” (fatigue, widespread musculoskeletal pain, complaints of cognitive difficulties, and subjective symptoms that are of such severity that, when present, they result in substantial reduction in previous levels of occupational, educational, social, or personal activities), yet evidence of viable spirochetes can be found in biopsies of ACA patients and the condition worsens unless the infection is properly addressed.

Additionally, patients with ACA may also have many of the symptoms included in the “post-Lyme syndrome” exclusion category. The IDSA’s “post-Lyme syndrome” exclusion criteria list includes, but is not limited to, the following signs and symptoms:

An active, untreated, well-documented coinfection, such as Babesiosis;objective abnormalities on physical examination or on neuropsychologic testing; antibiotic refractory Lyme arthritis; late neuroborreliosis associated with encephalopathy, recurrent or refractory objective cognitive dysfunction; a prolonged history of musculoskeletal pains or fatigue; a diagnosis of an underlying disease or condition that might explain the patient’s symptoms (e.g. morbid obesity; medications; autoimmune diseases; uncontrolled cardio-pulmonary or endocrine disorders; malignant conditions within 2 years; known current liver disease; any past or current diagnosis of a major depressive disorder with psychotic or melancholic features; bipolar affective disorders; schizophrenia of any subtype; delusional disorders of any subtype; dementias of any subtype; anorexia nervosa or bulimia nervosa; and active drug abuse or alcoholism at present or within 2 years); laboratory or imaging abnormalities that might suggest an undiagnosed process distinct from post–Lyme disease syndrome, such as a highly elevated erythrocyte sedimentation rate (150 mm/h); abnormal thyroid function; a hematologic abnormality; abnormal levels of serum albumin, total protein, globulin, calcium, phosphorus, glucose, urea nitrogen, electrolytes, or creatinine; significant abnormalities on urine analysis; elevated liver enzyme levels, or a test result suggestive of the presence of a collagen vascular disease; and a positive PCR result.

This also begs the question- If people with ACA were to be placed in a clinical trial, under which category would they be placed when the clinical trials for Lyme disease were beginning? They have signs, symptoms and documentation of active infection, as well as, signs and symptoms listed in the “post-Lyme syndrome” inclusion criteria, as well as, symptoms mirroring the symptoms in the exclusion category. The ACA presentation puts quite a big dent in the “post-Lyme syndrome” theory and certainly requires IDSA authors to take their Guidelines back to the drawing board if they intend for them to be scientifically and medically accurate.

While making adjustments for the ACA/post-Lyme situation, the Guideline authors may want to reconsider another aspect of the ACA presentation. Progressive allodynia (the exaggerated reaction to pain), is a symptom Guideline authors misunderstood in patients with Lyme disease, yet it is a well-documented, characteristic symptom of active disease progression and, thus, may be a clue to the diagnosis of chronic persisting Lyme disease, especially when accompanied or preceded by the presentation of acrodermatitis chronica atrophicans lesions.

Some have made the assumption allodynia was a condition related to some sort of mental illness in Lyme patients and for that reason they indicated patients were not actively infected, but instead, mentally ill often prior to contracting Lyme disease.

The mere existence of the ACA presentation proves them wrong. Rather than dismissing patient’s complaints and declaring them cured, or worse, mentally ill because they remain sick after treatment, perhaps a mention in the guidelines of the condition called allodynia and the fact it is associated with the ACA presentation caused by active infection would be appropriate.

The loss of hair, fragility of the skin and the compromised sweat glands associated with ACA leaves patients skin poorly protected and vulnerable. Bacterial super-infections in patients have occurred, adding to the patient’s pain and misery, not to mention the financial burden incurred by treating the additional symptoms.

With that in mind, the recommendation against treating Lyme patients due to a possible resistance problem goes right out the window for several reasons. Not treating patients and allowing them to reach the later stages of the disease is actually responsible for super-infections developing, via the complications associated with the ACA presentation.

In addition, the Guideline authors and their followers have previously admitted in other publications that treating Lyme patients for their Borrelia infections does not cause resistance problems in the early stages, making that claim mute.

Patients with ACA can experience acral pain, paresthesia, dysesthesia and cognitive dysfunction in conjunction with the ACA skin manifestations. Peripheral neuropathy, lymphadenopathy, musculoskeletal pains, and joint damage may also be complicating factors in these patients.

Destruction and deformity of the small joints of the hands and the feet is often seen along with, or independent of, additional complications and presentations, such as atrophy of the epidermis, morphea, lichen sclerosus atrophicus, facial edema, and paresis of the brachial plexus.

Fibrotic nodules or bands may be seen on the surfaces of the elbows and the knees. Edema with or without a bluish discoloration to the skin may occur, especially in the earlier stages.

Acrodermatitis chronica atrophicans has been described in association with localized amyloidosis, eczema, psoriasis, lupus erythematosus, leprosy, and Hodgkin disease. [i]

Without adequate testing, many Lyme patients have been misdiagnosed with diseases and conditions they do not have, instead of the proper diagnosis of acrodermatitis chronica atrophicans.

Scleroderma, livedo, venous insufficiency, Reynaud’s syndrome, edema and an ongoing aging process have taken the place as a diagnosis for patients who are suffering from ACA.

As scientific knowledge of the active disease progression in ACA becomes more apparent and is further documented, additional concerns can and are being raised.

Acrodermatitis chronica atrophicans (ACA) represents the persistent late stage of borreliosis in which Borrelia species may survive for decades. Occasionally, B-cell lymphoma may develop in these patients, and additional neoplastic complications such as basal cell carcinoma or squamous cell carcinoma (SCC) have been reported once each over the past 60 years.[ii]

The only treatment the Guidelines recommend for ACA is a three-week course of the same medication that failed Lyme patients previously and which put them in a chronic infectious state in the first place.

Recommendations in the Guidelines do nothing for acutely ill Lyme patients or the late stage ACA patients than suppress clinical judgment and restrict treatment options. Therefore, there should be no recommendations by the IDSA when the science is lacking and their experience is naught. The stakes are too high and the outcome for patients is bleak with the IDSA Guidelines in place.

The Guidelines state: “Atrophic areas often persist, and little objective improvement can be demonstrated in the neuropathy… However, progression of neurologic involvement is halted, and the neuropathic symptoms of pain and paresthesia are improved [251, 252].”

Throughout the IDSA Guidelines, authors recommend against antibiotic therapy and all other treatment options as a general rule, however, they consider it acceptable to treat a patient presenting with ACA symptomatically using antibiotics as the drug of choice.

This is only after patients have suffered with late stage disease to a point that there is little hope of reversing the damage, ending their pain or of achieving a complete recovery.

The lame and insulting three-week course of antibiotics is simply throwing more of the same medicine at a disease after it has been proven to be an unsuccessful protocol the first time around.

True, it is a “cost-effective” treatment, with an out-of-pocket expense of approximately $10.00, however, it is not effective. The money would be better spent on ice cream; at least there would be some temporary pleasure gained before patients realize they are in deep trouble, having no options left while dealing with an infectious disease that has run-a-muck.

There are no provisions in the IDSA Guidelines for those who fail to recover on the three weeks of “cost-effective” antibiotics offered for any stage of the disease. All doors that may lead to recovery or relief are shut tightly and patients and their health care providers are left with no viable options.

Medical guidelines and their authors have a responsibility to not increase suffering by their recommendations. Therefore, the practice of closing the door on all options must be addressed before more are endangered by IDSA Guidelines recommendations.

The Guidelines state: “There are no prospective, randomized studies on treatment.”

Throughout the Guidelines there is no foundation for many of the recommendations the IDSA authors propose or exclude, yet for the final stage of this menacing infectious disease, panel members are comfortable pulling an arbitrary treatment protocol out of thin air, calling it evidence-based science and recommending against anything but this precariously selected, previously unsuccessful, unsubstantiated treatment.

The authors have admitted their recommended three-week protocol can have substantiated risks associated with it- their reason for denial of antimicrobials earlier on in the disease- yet, without regard to their previously stated concerns, they recommend this treatment for the ACA, without hesitation and without documentation.

The Guidelines’ reference articles, provided at the end of the document, lack substance, especially concerning the clinical picture and treatment of ACA.

A simple search on Pub-Med produced 340 articles dating back to 1948 concerning the manifestations associated with ACA. A search on “chronic Lyme and ACA” produced 107 medical articles, also dating back sixty years. The Guideline authors relied on only three articles to support their ACA opinions, conclusions and recommendations.

The first referenced article was by Persing, et al. [iii] Persing is Vice-President and Director of Cepheid and the Director of Monogram Biosciences. Persing, according to Forbes [iv], pockets a million plus dollars a year income, and along with the IDSA authors and their cohorts, was involved in the failed Lyme vaccine fiasco. Persing is also a Lyme vaccine patent holder (USA #6,045,804) [v], and was an author on the original IDSA 2000 Lyme disease Guidelines. [vi]

Persing’s 1994 report on the ACA rash, which was used to support the IDSA author’s treatment recommendations, revolved around the charts of five (out of 6) European immigrants seen over a period of 49 years at a mid-western clinic between 1912 and 1961.

The notes and charts were generated long before Lyme disease was recognized as a complex infectious illness, before tests were developed to detect it, before the infectious organism responsible for the disease was discovered and before anyone knew how the disease was transmitted to humans.

The conclusions drawn from Persing’s paper were based on a handful of clinical notes and histopathological findings, with associated documents ranging in age between 45-94 years.

Considering the fact penicillin was not invented until 1928 and Doxycycline (6-Deoxy-5-hydroxytetracycline) was not clinically developed until the early 1960s by Pfizer, Inc., [vii] it seems highly unlikely the historical reminiscing in this article would have much to contribute to the foundation of the 2006 Guidelines treatment protocols for Lyme patients with ACA.

Some of the Guidelines reference authors, along with Persing, have been partners on Lyme related projects with the IDSA panel members. This is a cozy deal, no doubt, but guideline references based on nothing more than papers written by people with no experience treating patients successfully and nothing but massive amounts of additional conflicts of interest to add to the equation, the very reason for this guideline review, is not a sound basis for restricting treatment to patients and recommending they only receive more of what did not work for them previously. Persing’s inappropriate contribution to the ACA section should, therefore, be discarded.

The second article supporting treatment recommendations refers to untreated ACA patients from Sweden [viii], a huge disappointment considering over 300 studies were available to review that may have discussed actual treatment, some even generated from the United States, the author’s preferred venue.

If the Guidelines authors reviewed this Swedish article for information on ACA, they should have described the ACA presentation in their Guidelines and presented a complete picture in order to promote the use of clinical judgment and patient autonomy.

The Swedish article, published over ten years ago, should be discarded as a reference, as it contributed nothing to the treatment recommendations and the Guidelines authors did not report on the information concerning the ACA presentation.

The third article chosen by the IDSA panel was, unlike the others, at least written during this century, however, it is by the same Swedish authors found in the second article. The study determined their limited treatment protocol was unsuccessful in resolving many of the presentations accompanying chronic late stage ACA, stating in part:

Despite a good therapeutic effect on ACA lesions, specific antibody values and symptoms of irritative nerve lesions, the objective neurological and neurophysiological findings of nerve deficit remained unchanged. There was no progress of neuropathy findings during the follow-up time. [ix]

In contrast, the IDSA authors claim in the Guidelines that treatment for the ACA presentation:

…resulted in improvement in pain and swelling, diminution in fibrous nodules, and gradual fading of the lesion within 2–6 months [250–252]. Atrophic areas often persist, and little objective improvement can be demonstrated in the neuropathy in uncontrolled studies, regardless of whether antibiotics are administered parenterally…. progression of neurologic involvement is halted, and the neuropathic symptoms of pain and paresthesia are improved.

In 2009, a study mentioned below by Mullegger, et al, determined the diagnostic tests for Lyme were of very little value and that the clinical picture is the key to diagnosis and treatment efficacy concerning the ACA presentation.

One medical study discussing treatment of ACA being used as ‘the’ scientific foundation for making decisions does not allow for a well balanced, unbiased, sound recommendation for treatment.

If the IDSA authors must mention treatment recommendations for ACA, their sources should have substance, there should be more than one reliable source, clinical aspects must be considered and the recommendations made must be in conjunction with and include the best-known treatment available. If this cannot be accomplished, no recommendations should be made and all options should remain open.

The IDSA guidelines state: “Although any of the species of Lyme Borrelia may cause the lesion, by far the most common etiologic agent is B. afzelii. Therefore, this manifestation is much more common in Europe than in the United States [243– 246]. “

Rule one: If you don’t look for it, you won’t find it. Without clinical trials and properly educated practitioners experienced in recognizing and treating a specific condition and providing continual feedback, it is impossible to make the above determination.

As more evidence surfaces indicating serologic tests are inadequate for determining exposure to Borrelia, clinicians will be required to educate themselves and depend on their clinical skills to determine if ACA is a problem in the United States.

Patients report experiencing the ACA presentation in increasing numbers; however, they are unable to find physicians versed in the diagnosis and treatment of the condition.

As Mullegger’s study determined concerning ACA:

…repeated serologic testing is of very limited value for assessing therapy efficacy, and therefore not recommended in the follow-up of dermatoborrelioses patients. Since cultivation of the etiologic agent, Borrelia burgdorferi sensu lato, and polymerase chain reaction are also inadequate for this purpose, the assessment of patients with cutaneous manifestations of Lyme borreliosis in the follow-up rests primarily on the clinical picture.[x]

The Guidelines failure to include a full and complete assessment of the ACA presentation skews the clinician’s perception of the disease process and removes their ability to utilize clinical judgment in an advantageous manner.

The previous edition of the IDSA Guidelines (2000) allowed for the fact the authors were not educated about a specific Lyme related topic. For example, concerning ophthalmologic manifestations they stated:

Because of the lack of evaluable data on ophthalmologic complications, which are very rare, the panel was unable to make recommendations concerning keratitis and other possible ocular manifestations of Lyme disease.

Rather than recommend against specific treatments or limit treatment options, in this case they allowed for the fact the science had not provided them with definitive answers.

Patients, therefore, were able to seek treatment and be reimbursed by their insurance companies. Clinical judgment and patient autonomy were utilized in this case, as they should always be when discussing or making health care decisions.

Conclusion:

The IDSA Guideline authors and their supporters (as in the case of Persing) have failed to offer scientific validation for their diagnostic and treatment recommendations for the ACA presentation.

They indicate in the Guidelines they are unfamiliar with many complications and presentations associated with Lyme disease; they have no experience treating patients with ACA, do not recognize ACA and other conditions in their practice (those who actually treat patients) and have no scientific studies to substantiate their recommendations for ACA.

They reject the concept of “chronic” Lyme caused by active infection, therefore, in their eyes, ACA can not possibly exist. Rather than dismiss ACA, they offer a token treatment of 3 more weeks of antibiotics and leave patients stranded with no other options.

The authors simply contend that when the ACA condition presents itself years after the original Lyme diagnosis, after the disease has taken over and there is no hope of complete remission, no hope for a reversal of symptoms or a cure, that an additional three weeks of the same antibiotic that failed the patient in the past and which led to this chronic stage of illness, be a final offering of good faith.

The mere presence of ACA in previously treated patients, years after what was thought to be “adequate treatment”, indicates Lyme disease can be a chronic infectious disease.

Multiple Borrelia species in Europe and the United States have the ability to remain sequestered from both antimicrobials and the immune system, hiding in immune-privileged sites, allowing for the development of ACA years after people are exposed, therefore, the section making recommendations against alternative treatments and the entire misleading and unsubstantiated ACA section should be deleted from the IDSA Guidelines.

In addition, clinical judgment and patient autonomy should be emphasized.

Please refer to Part II of this challenge, which includes related photographs.

Prepared and submitted by:

Lyme Disease Education and Support Groups of America

AfterTheBite@gmail.com

Contact: Lucy Barnes

References

[i] Bozena Chodynicka, Bozena MD, Schwartz, Robert A. MD, MPH. Acrodermatitis Chronica Atrophicans. Medscape, WebMD, 23 Mar. 2009 http://emedicine.medscape.com/article/1051695-overview

[ii] Leverkus M, Finner AM, Pokrywka A, Franke I, Gollnick H. Metastatic squamous cell carcinoma of the ankle in long-standing untreated acrodermatitis chronica atrophicans. Dermatology. 2008;217(3):215-8. Epub 2008 Jul 8.

[iii] DiCaudo DJ, Su WP, Marshall WF, Malawista SE, Barthold S, Persing DH. Acrodermatitis chronica atrophicans in the United States: clinical and histopathologic features of six cases. Cutis 1994; 54:81–4. 270.

[iv] Forbes. David H. Persing. Sunnyvale , CA. Sector: TECHNOLOGY http://people.forbes.com/profile/david-h-persing/17388

[v] Persing, David H. US Patent 6045804 - Method for detecting B. burgdorferi infection. No. 612231 filed on 03/07/1996 http://www.patentstorm.us/patents/6045804.html

[vi] Wormser, G. P., R. B. Nadelman, R. J. Dattwyler, D. T. Dennis, E. D. Shapiro, A. C. Steere, T. J. Rush, D. W. Rahn, P. K. Coyle, D. H. Persing, D. Fish, B. J. Luft, et al. 2000. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin. Infect. Dis. 31:(Suppl. 1):1-14.

[vii] E-Med Expert. Doxycycline (Doryx) Medical Facts. http://www.emedexpert.com/facts/doxycycline-facts.shtml

[viii] Kindstrand E, Nilsson BY, Hovmark A, Pirskanen R, Asbrink E. Peripheral neuropathy in acrodermatitis chronica atrophicans—a late Borrelia manifestation. Acta Neurol Scand 1997; 95:338–45.

[ix] Kindstrand E, Nilsson BY, Hovmark A, Pirskanen R, Asbrink E. Peripheral neuropathy in acrodermatitis chronica atrophicans—effect of treatment. Acta Neurol Scand 2002; 106:253–7. 276.

[x] Mullegger RR, Glatz M. Is Serological Follow-Up Useful for Patients with Cutaneous Lyme Borreliosis? Curr Probl Dermatol. 2009;37:178-182.. Chodynicka, Bozena MD, Head, Professor, Department of Dermatology and Venereology, Medical University of Bialystok, Poland. Schwartz, RA, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Flisiak, Iwona, assistant, MD, Department of Dermatology and Venereology, Medical University of Bialystok, Poland. Acrodermatitis Chronica Atrophicans. Mar 23, 2009 http://emedicine.medscape.com/article/1051695-overview

Please refer to Part II of this challenge, which includes related photographs.