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Bullous Pemphigoid

Bullous pemphigoid is a rare autoimmune disease of the elderly, characterized by bullae formation on mucocutaneous surfaces.


Presentation

The main presentation of bullous pemphigoid is a large acute or subacute skin blister within the armpit, lower abdomen and thigh. Sometimes, pruritus may be the only inaugural symptom felt especially among the older sets of patients [5].

The blister often contains a clear liquid with some blood and are not easily ruptured when poked by the fingers. The skin surrounding the blisters may appear normal or reddened.

The blistering disease usually occurs along the lines of the creases and skin folds but may rarely occur on the lips and eye mucosa. These lesions are usually very itchy and may cause long term discomfort.

Limb Pain
  • She started dapsone at the dosage of 1 mg/kg/day, maintaining low dose prednisone; this treatment was successfully followed by the dramatic disappearance of skin lesions and limb pain.[ncbi.nlm.nih.gov]
Gaucher Disease
  • Gaucher disease (GD) is a rare genetic lysosomal storage disorder inherited in an autosomal recessive pattern. GD is due to the deficiency of a lysosomal enzyme, acid beta-glucosidase (or glucocerebrosidase).[ncbi.nlm.nih.gov]
Pertussis
  • Two of them developed an eruption of bullous lesions just a few days after vaccination for diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae B.[ncbi.nlm.nih.gov]
Arthralgia
  • She showed bullous skin lesions with arthralgia, mild proteinuria, resolved after steroid treatment. At the tapering of her prednisone dose, the patient had new skin lesions requiring an increased dose of prednisone.[ncbi.nlm.nih.gov]
Blister
  • CD11b was also increased in BP blood eosinophils, which may explain the striking accumulation of eosinophils in BP (1 106 per ml blister fluid). Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in blister fluid.[ncbi.nlm.nih.gov]
  • In most cases, there are blisters, called bullae. Blisters are usually located on the arms, legs, or middle of the body. Some people develop blisters in the mouth. The blisters may break open and form open sores ( ulcers ).[nlm.nih.gov]
  • The blister often contains a clear liquid with some blood and are not easily ruptured when poked by the fingers. The skin surrounding the blisters may appear normal or reddened.[symptoma.com]
Pruritus
  • […] for BP are warranted in patients treated with checkpoint inhibitors who develop intractable pruritus.[ncbi.nlm.nih.gov]
  • Furthermore, lesions that may accompany the pruritus are heterogeneous. The term nonbullous BP seems adequate but lacks the most important clinical characteristic: pruritus.[jamanetwork.com]
  • This delay is associated with torturous pruritus and severe impact on patients’ quality of life.[skin.ern-net.eu]
Eczema
  • Dyshidrotic pemphigoid (DP) is a rare variant of bullous pemphigoid (BP) that affects the hands and feet and may resemble an acute vesicular eczema. While it can remain confined to hands and feet, spread that involves the entire body is described.[ncbi.nlm.nih.gov]
  • Symptoms of bullous pemphigoid Bullous pemphigoid may first look like hives or eczema, because it can be red and itchy. Large blisters may then form. These blisters are often filled with a clear liquid. They may feel very itchy.[saintlukeskc.org]
  • It usually starts with a red, itchy rash that resembles eczema or hives. Itchy blisters can then appear that tend to last weeks or months. Mouth sores and bleeding gums are other symptoms.[cbc.ca]
Urticaria
  • Clinically, BP is characterised by generalised pruritic, bullous eruptions and urticaria-like lesions. Usually, BP is an idiopathic disorder; however, in some cases, underlying internal disorders are present, like diabetes or neurological disorders.[ncbi.nlm.nih.gov]
  • Bullous pemphigoid can look initially like dermatitis or urticaria (hives) with red itchy bumps and patches. Unlike hives, these patches do not move around or disappear.[dermcoll.edu.au]
  • In this case there was no urticaria (hives) or eczematous rash and minimal itch1. Some of the blisters contained clear fluid while others contained bloodstained fluid.[eakin.eu]
  • […] membranes Antibodies bind to epidermal side in salt split skin test Antibodies on formalin fixed paraffin embedded tissue less sensitive Type IV collagen can be detected on blister floor (in contrast to EBA) Differential diagnosis Early lesions can resemble urticaria[pathologyoutlines.com]
  • BP is characterized initially by the development of diffuse eczematous, pruritic, urticaria-like lesions, with the later appearance of tense bullae or blistering lesions typically filled with clear fluid.[cureus.com]
Nikolsky's Sign
  • Placing pressure on the bullae do not lead to their extension into underlying skin, and thus the bullae are negative for "Nikolsky Sign".[pathwaymedicine.org]
  • The Nikolsky sign, where upper layers of epidermis move laterally with slight pressure or rubbing of skin adjacent to a blister, is negative.[msdmanuals.com]
  • Nikolsky's sign is negative, unlike pemphigus vulgaris, where it is positive. In most cases of bullous pemphigoid, no clear precipitating factors are identified.[en.wikipedia.org]
  • Blister formation occurs between the stratum spinosum and stratum basale, creating thin, easily ruptured lesions with a positive Nikolsky sign.[consultant360.com]

Workup

The definitive diagnosis of bullous pemphigoid relies heavily on the accurate clinical history of the patient and the careful physical examination of the lesion by the physician. In some instances, dermatologist may require to harvest a small part of the lesion for biopsy.

Microscopic examination may differentiate bullous pemphigoid from the more common and benign bulluos vulgaris by identifying the skin layer where the immune response concentrates.

Complement and IgG antibodies have been found to appear in a linear arrangement in the basal membrane of the skin which heralds the classical diagnosis of Bullous pemphigoid [6].

Immune assay like the Enzyme Linked Immunosorbent Assay (ELISA) can demonstrate the qualitative and quantitative occurrence of BPAg1 and BPAg2 which aids in the definitive diagnosis of the disease [7].

Anergy
  • In a patient with dysregulation of Th1/Th2 balance, anergy is lost and T-cells are subsequently primed resulting in the development of functional autoimmunity against the BP180-NC16a domain leading to clinically overt disease. 2017 John Wiley & Sons A[ncbi.nlm.nih.gov]
Enlargement of the Liver
  • Type 1 Gaucher disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen, and liver as well as bone complications (Erlenmeyer flask deformity, osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts, and avascular[ncbi.nlm.nih.gov]

Treatment

The cornerstone in the treatment of bullous pemphigoid is the immediate relief of the itching symptoms and the gradual resolution of the bullae.

Corticosteroid ointments may be rubbed on the lesion to reduce inflammation and itching while oral corticosteroids like prednisone can reduce inflammatory response within the lesion.

Chronic use of oral corticosteroid however may result into brittle bones and aggravate Diabetes mellitus [8]. Immunosuppressants like azathioprine may inhibit the body’s defenses to attack the bullae area but may also reduce the capacity of the white blood cells to defend the body from bacterial and viral invasions.

Antiinflammatory agents may be used singly or in combination with steroid to control inflammation. Examples of these common antiinflammatory agents includes methotrexate, and dapsone [9]. The use of tetracycline and niacinamide has been found to control bullous pemphigoid but not in bullous foliaceus [10].

Prognosis

Bullous pemphigoid may spontaneously resolve within 3 to 6 years even without medications. The older and debilitated patients however, may suffer lethal consequences in a third of these cases. There is an alarming increase in the mortality rate in bullous pemphigoid among chronic steroid users.

Complications

Bullous pemphigoid can rarely occur in the eyes and the mucus membrane of the mouth. These types of blistering disease may rupture and cause scarring and disfigurement to the patient. Large bullous may erupt and cause an ulcer which can be easily infected by pathogenic bacteria especially in old and debilitated patients. The secondary spread of bacteria may become an overwhelming sepsis which could be life-threatening.

Etiology

The direct cause of bullous pemphigoid remains elusive but these drugs have been shown to trigger its occurrence: Penicillin, Sulfasalazine, Furosemide, Spironolactone and antipsychotic drugs.

Radiotherapy of certain organs and exposure to ultraviolet light are among the few physical causes of bullous pemphigoid. Patients with recent radiotherapy have been observed to have an increasing incidence of bullous pemphigoid [1]. Autoimmune disorders like Rheumatoid Arthritis, Diabetes mellitus, and Multiple Sclerosis are also implicated to co-exist with this bullous lesion.

Epidemiology

The incidence of bullous pemphigoid is grossly infrequent internationally. Cases in France and Germany have been recorded at 6.6 cases per million population per year. Although identified as a rare disease, bullous pemphigoid is still considered as the most common subepidermal autoimmune blistering disease in Europe.

In cohort studies done in the United Kingdom, bullous pemphigoid cases are found to exist in 4.3 cases per 100,000 population [2]. In a study in Switzerland, the case fatality rate of bullous pemphigoid has been seen to increase among its respondents [3].

Sex distribution
Age distribution

Pathophysiology

The pathophysiology of bullous pemphigoid lies on the autoimmune response and inflammation at level of the basement membrane of the skin. The autoantibodies IgG initially bind to the basement membrane activating the complement system to attract inflammatory cells in the membrane. These inflammatory cells release proteases which degrades the protein within the skin layer that subsequently results in a blister.

Histopathologic diagnosis reveals eosinophilia in the area but the role of eosinophils in the blister formation are still unclear. The Bullous pemphigoid antigens (BPAg1 and BPAg2) have been carefully studied as an active factor in the induction of bullous pemphigoid in man and animals [4].

Prevention

Bullous pemphigoid being an insidious autoimmune disease may be difficult to prevent. The list of medication listed to cause the bullous lesion should be taken with caution and care. If these medications are totally indicated, patients should be vigilant enough to monitor high risk regions of the body for its occurrence.

Patients with the primary lesion, should avoid puncturing the bullae to prevent the spread of infection. Due diligence should be directed towards the regular compliance of prescribed medications to shorten its clinical course and prevent untoward complications.

Summary

Bullous pemphigoid is an autoimmune disorder where the patient’s immune system attacks the subepidermal layer of the skin causing a bullous blister. These blisters occurs in the area of the lower abdomen, upper thighs and armpits.

The true nature of the aberrant immune response is still unknown although some medications have been implicated to trigger the disease. Bullous pemphigoid may be fatal to the elderly and debilitated patients.

Patient Information

The active and conscious protection of the blister from inadvertent rupture is of paramount importance. In the event of a rupture, patients should put protective dressing and diligently clean the ulcer to prevent spread of infection to contiguous parts of the body.

Bullous pemphigoid lesions should be shielded from the direct exposure to the sun because the ultraviolet light and radiation aggravates the condition. Patients suffering with mouth lesions should avoid eating hard foods like nuts, dried fruits and chips to prevent the untimely puncture of the bullous lesion.

References

Article

  1. Isohashi F, Konishi K, Umegaki N, Tanei T, Koizumi M, Yoshioka Y. A case of bullous pemphigoid exacerbated by irradiation after breast conservative radiotherapy.Jpn J Clin Oncol. 2011; 41(6):811-3
  2. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: population based cohort study. BMJ. Jul 9 2008; 337:a180.
  3. Cortes B, Marazza G, Naldi L, Combescure C, Borradori L. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol. Aug 2011; 165(2):368-74.
  4. Xu L, Robinson N, Miller SD, Chan LS. Characterization of BALB/c mice B lymphocyte autoimmune responses to skin basement membrane component type XVII collagen, the target antigen of autoimmune skin disease bullous pemphigoid. Immunol Lett. Jun 1 2001;77(2):105-11.
  5. Cortes B, Marazza G, Naldi L, Combescure C, Borradori L. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol. Aug 2011;165(2):368-74
  6. Andrachuk L, Ghazarian D, Siddha S, Al Habeeb A. Linear arrangement of neutrophils along the Basal layer in bullous pemphigoid: a unique histological finding. Am J Dermatopathol. 2012; 34(2):192-3 (ISSN: 1533-0311)
  7. Roussel A, Benichou J, Randriamanantany ZA, Gilbert D, Drenovska K, Houivet E, Tron F, Joly P. Enzyme-linked immunosorbent assay for the combination of bullous pemphigoid antigens 1 and 2 in the diagnosis of bullous pemphigoid. Arch Dermatol. 2011; 147(3):293-8 (ISSN: 1538-3652)
  8. Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. N Engl J Med. Jan 31 2002; 346(5):321-7.
  9. Tirado-Sánchez A, Díaz-Molina V, Ponce-Olivera RM. Efficacy and safety of azathioprine and dapsone as an adjuvant in the treatment of bullous pemphigoid. Allergol Immunopathol (Madr). 2012; 40(3):152-5 (ISSN: 1578-1267)
  10. Shiohara J, Yoshida K, Hasegawa J, Uhara H, Takata M, Saida T, Ohyama B, Oyama B, Hashimoto T. Tetracycline and niacinamide control bullous pemphigoid but not pemphigus foliaceus when these conditions coexist. J Dermatol. 2010; 37(7):657-61 (ISSN: 1346-8138)

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Last updated: 2019-07-11 21:29