Case study: a memorable case of bullous pemphigoid

Dermatological disease in older patients poses unique challenges that need to be appreciated in order to successfully manage the patient. The older population as a whole tends to have more comorbidity, is frailer and is often in a more precarious social situation. It may only be through experience that some of the potential pitfalls can be understood and avoided.

In this essay, I will review a case of a gentleman with bullous pemphigoid that I experienced during my CMT rotation in dermatology. I will then take a brief look at the disease and treatment guidelines before concluding with the lessons to be learnt.

The case in question

I am reminded of a 77-year-old gentleman with a background of dementia and severe oesophageal dysmotility, who was admitted to hospital following one of a number of falls. He was making recovery from this when the longstanding excoriation over his body began to blister. He was referred to and reviewed by the on-call dermatology team.

Looking back through his history, this gentleman had been seen by dermatology eight months beforehand with non-blistering excoriations. At the time, he was thought to be suffering from dermatitis with an element of artefactual change after a negative indirect immunofluorescence. Skin biopsy was considered, but the decision was made not to proceed as it was thought that this would not alter management.

On this admission, a clinical diagnosis of bullous pemphigoid was made and a biopsy was taken from one of the blisters. He was started empirically on topical dermovate ointment BD. Under the closely monitored inpatient environment, the patient made a quick and substantial improvement with no new blisters after a matter of days. He was in hospital for many weeks for social reasons during which time no new blisters formed. He was discussed in a consultant meeting and the decision was made not to start him on oral medication. This was because his condition was well controlled on topical therapy and it was thought best to avoid any unintended side effects. He was discharged home, where he lived with his wife and no carers, with what was thought to be a clear topical therapy plan.

Unfortunately, three weeks later the patient’s GP rang the department due to an uncontrolled flare of the condition. At this point advice was given to start on oral prednisolone, pending emergency dermatology appointment the following week.

When attending this appointment it was clear that his condition had deteriorated significantly. He was very unsteady on his feet, requiring assistance from staff members to hold him up, and his clothing was extensively soiled. He had come by taxi but had not bought enough money for a return journey; his plan having been to walk home afterwards. It seemed that the gentleman had been having difficulty applying topical therapy and he was not taking the prednisolone as advised (he had not even picked these up from a pharmacy), though he was unable to give clear answers.

His erosions were extensive, involving his forearms, hands, forehead, thighs and feet. He was initiated on doxycycline 200mg OD, prednisolone 20mg OD and the BD dermovate was re-instated. Consideration was given to a higher dose of prednisolone, but due to his comorbidities it was decided to use a lower dose initially, especially in view of avoiding any psychotropic effects.

Once this was started his skin rapidly improved and four days later, on review, there were no new blisters. At this point the biopsy from the first admission had come back confirming the diagnosis. Unfortunately, his dementia seemed to deteriorate even on this low dose of prednisolone, requiring chemical restraint at one point, but it was felt that this needed to continue on a clinical basis.

He has since gone home on 15mg prednisolone and 200mg doxycycline in addition to his topical therapy. We hope that this is enough to keep the disease at bay but will keep him under close review and have ensured the wife has a clear helpline number and topical instructions. Despite the previous issues, his wife was reluctant to accept help at home and so they remain at home unaided.

What is bullous pemphigoid?

Bullous pemphigoid is an autoimmune skin condition that normally occurs in older patients with a mean age of onset of 80 years, it occurs equally in males and females.¹ Interestingly it seems to be more prevalent in those with neurological diseases such as stroke, dementia (including, as in our patient fronto-temporal dementia) or Parkinson’s disease.^2,3There are various mechanisms proposed for this association.

The pathophysiology of the disease is an attack on the basement membrane of the epidermis by IgG plus or minus IgE immunoglobulins and activated T lymphocytes. The target is a protein BP180 or occasionally BP230, both part of collagen XVII, associated with hemidesmosomes. It is the breakdown of these hemidesmosomes that leads to sub-epidermal blister formation.⁴

As in this gentleman, patients often have a non-specific or eczematous-like rash several weeks prior to blister formation. The disease can lead to morbidity and mortality from infection, treatment complications or from underlying/associated disease.⁵

Treatment guidelines for bullous pemphigoid

The latest treatment guidelines from The British Association of Dermatologists were issued in 2012. In it they advise that treatment involves one or a combination of topical/systemic steroids, steroid sparing medication or antibiotics. The recommended initial dose of prednisolone is 0.5mg/kg/day which is slowly tapered down. Typical steroid sparing medication could include tetracycline antibiotics such as doxycycline, dapsone, nicotinamide, methotrexate, azathioprine, mycophenolate, intravenous immunoglobulin or rituximab.⁶ The length of treatment can often be several years but the disease normally clears, at which point treatment can be stopped.

Lessons to be learned

This case raises several important lessons regarding skin disease and the older patient. This gentleman’s disease was well controlled during his inpatient stay; however, on discharge it rapidly flared. One possible explanation for this is that the patient was not having topical therapy in the community.

This highlights that in cases where it is suspected that the patient is unable or unwilling to comply with topical therapy. It is important to ensure that another family member or carer is well educated on the importance of appropriate application. It may be that someone in the household is capable of this but is unaware of its importance and so it is not adhered to. Perhaps in this case, the disease and its treatment were not explained sufficiently to the wife by the dermatology team.

Alternatively, the patient or relative may be incapable of applying the topical therapy, in which case an alternative method of application or treatment must be sought. As this may involve acquiring carers or even a move to supported living, serious thought should be given to alternative treatment modalities such as oral systemic medication. In this case, the wife may have been unable to apply his topical treatment in which case we may have given greater consideration to oral medication sooner or made a greater argument for carers to be sourced.

The normal recommended dose of prednisolone in the treatment of bullous pemphigoid is 0.5mg/kg/day. However, we should be reminded in the comorbid of the importance to consider the extensive side-effect profile.⁷ In our patient we reduced the initial dose and it still seemed to have an impact on his mental state, resulting in chemical restraint and subsequently a hypoactive delirium.

Although some of this may be attributable to the change in his environment, this wasn’t seen on his initial admission when he was not on any corticosteroids. Related to this, it must be remembered that the timing of steroid administration should be in the mornings if possible to avoid disruption to the sleep cycle. Recent evidence has highlighted the effectiveness of steroid sparing agents such as doxycycline, and perhaps we could have tried this on its own initially before using prednisolone, though this will remain a matter for debate.⁸

Finally, it is possible that the extent of deterioration could have been avoided if the patient or the family had felt empowered to seek immediate help directly from the dermatology team. Instead they went via their GP, resulting in several weeks delay, so that by the time the gentleman was seen by dermatology, his condition had already significantly deteriorated and required more radical treatment.

Conclusion

In conclusion, it appears that there are many lessons to be learnt for this case that can mostly be summarised by ensuring that a holistic approach is adopted for the older patient with dermatological disease. There are additional considerations to take into account in the elderly that may not arise in everyday dermatological practice, though are well recognised by geriatricians.

Only by considering the challenges that will be faced can they be taken into account and evaded. Certainly, I shall remember this patient and have already taken these lessons with me to apply to similar patients. Through this, I hope to achieve better outcomes than we did initially for this gentleman.

For more articles on rashes and skin condition go to our dermatology section

Jaimie Oldham, Guy’s and St Thomas’ NHS Trust

This article was the joint winning entry for the British Society for Geriatric Dermatology Kligman Essay Competition 2020.

References

1. Messingham KN, Miller AD, Narayanan NS, et al. Demographics and Autoantibody Profiles of Pemphigoid Patients with Underlying Neurologic Diseases. J Invest Dermatol 2019; 139(9): 1860-66
2. Papakonstantinou E, Limberg MM, Gehring M, et al. Neurological disorders are associated with bullous pemphigoid. J Eur Acad Dermatol Venereol 2019; 33(5): 925€“29
3. Katisko K, Kokkonen N, Krüger J, et al. The Association Between Frontotemporal Lobar Degeneration and Bullous Pemphigoid. J Alzheimers Dis 2018; 66(2): 743-750
4. Liu Z, Diaz LA. Bullous pemphigoid: end of the century overview. J Dermatol 2001; 28(11): 647-50
5. Barrick BJ, Lohse CM, Lehman JS. Specific causes of death in patients with bullous pemphigoid as measured by death certificate data: a retrospective cohort study. Int J Dermatol 2015; 54(1): 56-61
6. Venning VA, Taghipour K, Mohd Mustapa MF, et al. British Association of Dermatologists’ guidelines for the management of bullous pemphigoid 2012. Br J Dermatol 2012; 167(6): 1200-14
7. Naber D, Sand P, Heigl B. Psychopathological and neuropsychological effects of 8-days’ corticosteroid treatment. A prospective study. Psychoneuroendocrinology 1996; 21(1): 25-31
8. Williams HC, Wojnarowska F, Kirtschig G, et al. UK Dermatology Clinical Trials Network BLISTER Study Group. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet 2017; 389(10079): 1630-38