The Magic of the Dead Sea on Resistant Psoriasis

I first met EJ when he was 28 years old, a full 15 years after he was initially diagnosed with psoriasis and started on topical steroids. His initial treatments were largely unsuccessful, as EJ had significant, thick plaques that proved to be resistant to treatment.

At age 20, EJ was diagnosed with psoriatic arthritis (PsA) and started on a combination of adalimumab and methotrexate. While this drug combination kept his joint disease in check, it had minimal effect on his psoriasis. He was therefore switched to golimumab, again with no impact on his skin disease.

When we first met, EJ had one of the most aggressive cases of psoriasis I had ever seen, covering more than 40% of his body, including the genital area. Needless to say, this was a major social burden for EJ, and he was desperate to find anything that might help.

Approximately 5 years ago, EJ started to take month-long trips to the Dead Sea to experiment with climatotherapy, an alternative treatment method focused on the healing qualities of natural resources. Water in the Dead Sea has high salt content (346 g/L), along with numerous other minerals present in high concentrations such as manganese, copper, iron, sodium bicarbonate, and calcium chloride. Several small trials have been completed evaluating the effectiveness of Dead Sea climatotherapy on psoriasis patients, with most showing close to 50% skin clearance.1

Why is Dead Sea climatotherapy thought to work? One theory is that the high salt concentration in the Dead Sea leads to a release of pro-inflammatory and chemotactic mediators. In one study, the high magnesium chloride (MgCl2) concentration of this water was shown to dramatically influence the antigen-presenting capacity of Langerhans cells.2

It is generally believed that the unique solar ultraviolet (UV) spectrum in the Dead Sea basin contributes to its health benefits. Solar radiation at the Dead Sea is filtered due to its being located 400 meters below sea level, and it has been shown that the shortest part of UVB does not arrive at the Dead Sea. The combination of regular exposure to the sun at this low sea-level depth and the high mineral concentration of the water has been shown to be effective for the treatment of many common skin conditions, including psoriasis and eczema. Further studies have been performed on patients with vitiligo, ankylosing spondylitis, and other autoimmune conditions.3,4

Following his periodic trips that involved 30 days of sun exposure and skin treatment with the mud from the Dead Sea, EJ would always come back with completely clear skin. This would usually last about 2-3 months, but then his psoriasis would return in full force despite the variety of medications that we tried.

At a visit approximately 2 years ago, EJ came in with a rash at its all-time worst. He was being managed with a regimen of etanercept, MTX, and folic acid after having failed adalimumab and golimumab. With this third anti-TNF failure, we certainly thought this was the last time we’d circle back to the largest class of biologics used to treat PsA.

After a full workup, we opted next for ustekinumab. After an initial injection, it was time for another of EJ’s Dead Sea visits. To help keep his arthritis in check, we upped his MTX dose to 25 mg weekly.

When EJ returned, his psoriasis had, as usual, disappeared, and his arthritis was also well controlled, with no tender or swollen joints. We certainly were hopeful that these improvements were attributable to more than just climatotherapy, but we could only wait and hope.

At the “dreaded” 3-month mark that in previous years had been accompanied by a return of EJ’s psoriasis, this time, there was no such rebound. EJ was doing so well that we tapered his MTX down to 10 mg weekly along with continuation of his ustekinumab.

The next 3 months continued to go smoothly, with no skin issues. It was his arthritis and not his psoriasis that then became an issue, as EJ developed Achilles tendinitis and dactylitis as well as neck and low back pain. An MRI of the cervical spine showed perifacet edema and signs of early inflammatory changes. Because EJ’s psoriasis was doing so well, we were in a tricky spot, not wanting to upset our progress in that area while knowing we needed to do something for his arthritis.

It was time for an outside-of-the-box approach, and so we decided to add apremilast to EJ’s current combination of ustekinumab and MTX (I separated EJ’s diagnosis into psoriasis and PsA to get insurance approval for this combination). While current clinical guidelines do not recommend the use of apremilast in combination with other biologic therapies, there are case reports and retrospective studies showing that these combinations can control disease activity without an increase in the rate of infection.5 In addition to everything else, we initiated low-dose prednisone to temporarily ease EJ’s joint discomfort.

While improvements in EJ’s arthritis were noted within the next month, the pendulum swung again in the other direction as his psoriasis began to flare, soon covering approximately 10% of his body surface area. Discontinuation of the prednisone also caused complications, with worsening bilateral plantar fasciitis on top of multiple joint dactylitis.

It was time for further medication modifications, only this time another complication arose—EJ lost his insurance and could not afford to pay out of pocket for any biologic. Fortunately, we were able to link EJ to free medication programs, which allowed him to restart on adalimumab and continue with his apremilast. The MTX was also continued.

Not long after this latest medication modification, it was time for another climatotherapy visit to the Dead Sea. It followed the same pattern as most years—complete clearance of psoriasis for 3 months until the return of the first initial patches. Instead of immediately jumping to a different regimen, we held strong with the combination of adalimumab, apremilast, and MTX, this time since EJ’s arthritis was under good control. We did try adding a topical steroid, with minimal results. EJ’s psoriasis unfortunately continued to worsen and, since he was still without insurance, a referral for ultraviolet light therapy was out of the question.

So now what? EJ had tried and failed multiple anti-TNFs, along with an interleukin (IL)-23 inhibitor. We therefore decided to move to secukinumab, an IL-17 inhibitor. EJ again was fortunate enough to successfully enroll in the manufacturer’s free drug program. He has only just received his first loading dose, so it’s too early to gauge any effectiveness. I am also considering switching EJ from MTX to leflunomide as well if things continue to go south. While leflunomide has not demonstrated effectiveness in reducing the burden of psoriasis, it has some efficacy in the treatment of PsA.6

In their lifetime, the majority of patients with psoriasis and PsA will rotate through multiple medications, including traditional DMARDs, biologics, topical agents, and more. It is important that we understand the social and personal burden of psoriasis and PsA, along with the stigma and shame that may be associated with these diseases. Thankfully, we have a large arsenal of medications and topical therapies that can help most of our patients. It is also important that both rheumatology and dermatology providers work together to explore all treatment available for our patients, including UV light treatment as well as skin ointments and other alternative treatments such as climatotherapy.

References

  1. Hodak E, Gottlieb AB, Segal T, et al. Climatotherapy at the Dead Sea is a remittive therapy for psoriasis: combined effects on epidermal and immunologic activation. J Am Acad Dermatol. 2003;49(3):451-7.
  2. Schempp CM, Dittmar HC, Hummler D, et al. Magnesium ions inhibit the antigen-presenting function of human epidermal Langerhans cells in vivo and in vitro. Involvement of ATPase, HLA-DR, B7 molecules, and cytokines. J Invest Dermatol. 2000;115(4):680-6.
  3. Schallreuter KU, Moore J, Behrens-Williams S, Panske A, Harari M. Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS). Int J Dermatol. 2002;41(8):482-7.
  4. Codish S, Dobrovinsky S, Abu Shakra M, Flusser D, Sukenik S. Spa therapy for ankylosing spondylltis at the Dead Sea. Isr Med Assoc J. 2005;7(7):443-6.
  5. AbuHilal M, Walsh S, Shear N. Use of apremilast in combination with other therapies for treatment of chronic plaque psoriasis: a retrospective study. J Cutan Med Surg. 2016;20(4):313-6.
  6. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med. 2017;376(21):2095-6.

 

Monica Richey,NP, MSN,ANP-CP/GNP
Monica Richey, NP, MSN, ANP-CP/GNP is a nurse practitioner at the Division of Rheumatology at Northwell Health in New York, New York, and is the Advocate Member At-Large for the RheumatologyNurses Society.

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