Development of bullous pemphigoid during the haemodialysis of a young man: case report and literature survey

Haemodialysis is the most frequent form of renal replacement therapy (RRT) in patients with end‐stage renal disorder (ESRD). Patients with ESRD frequently develop skin problems, mainly xerosis, pruritus and hyperpigmentation, as well as bullous diseases, mainly porphyria or pseudoporphyria and, in some cases, bullous pemphigoid (BP). BP is the most common autoimmune sub‐epidermal blistering disease, and it predominantly affects elderly people. 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. Herein, we present a 33‐year‐old man with ESRD, maintained on haemodialysis, who developed BP. There are only six cases with BP provoked by the placement of a fistula for haemodialysis. BP in the current patient was confirmed by direct immunofluorescence (DIF) and indirect immunofluorescence using BIOCHIP. The patient responded promptly to tertracycline and 0·05% clobetasol propionate lesionally. However, the relationship between BP and the fistula for haemodialisys still remains unknown. It is highly likely that the skin injury associated with fistula placement was responsible for the alteration of the basement membrane zone (BMZ) and the stimulation of the immune system, leading to BP development. To explain the real role of fistula placement as a provocative factor in BP, other such cases are required for assessment.     

A Practical Approach to Treating Autoimmune Bullous Disorders with Systemic Medications

The bullous diseases comprise a heterogeneous group of skin disorders with distinct clinical and histological findings. They are characterized histologically by clefts at varying depths in the skin and are pathologically caused either by congenital defects or autoantibodies. Autoimmune bullous disorders are chronic conditions with significant morbidity and mortality in untreated patients. With the advent of immunosuppressive medications, mortality from these diseases has decreased significantly. However, complications from therapy itself are common causes of morbidity in these patients. Therefore, treatment of autoimmune bullous diseases is a challenge, as patients must remain on chronic medications with side effects that limit their use. This article aims to provide a practical approach to understanding the available medications for the treatment of autoimmune bullous diseases.     

Une présentation rare du syndrome d’intolérance au greffon renal : la pemphigoïde bulleuse

Bullous pemphigoid is an autoimmune bullous cutaneous disease. We report the case of a 60 year-old male patient whose kidney allograft failed and was on hemodialysis for the previous 16 months. After tapering immunosuppressive medication, he presented simultaneous bullous eruption and kidney allograft intolerance syndrome. Investigation showed a positive BP180 anti-basement membrane zone antibody and skin biopsy was consistent with bullous pemphigoid. The patient was treated with corticotherapy and bullous pemphigoid resolved. The development of new onset diabetes and concerns over long term immunosuppression, halted the decision to continue corticotherapy and the patient underwent graft nephrectomy, with resolution of the kidney allograft intolerance syndrome without recurrence of the bullous disease. The occurrence of bullous pemphigoid in patients with failed renal allograft is rare, with only eleven cases reported in literature. This case illustrates how graft nephrectomy can provide a definitive cure to bullous pemphigoid in this setting.     

Gastric Cancer and Paraneoplastic Pemphigus

Paraneoplastic pemphigus is a relatively rare but significant acquired autoimmune mucocutaneous disorder that is characterised by diffuse erythema, painful blistering and sores of the skin and mucus membranes. The underlying pathogenesis is believed to be triggered by altered immune system in response to underlying neoplasm. The manifestations can predate, occur at the same time or after the diagnosis of cancer. Associations with gastric cancer have only been reported twice. A 78-year-old lady presented with a month’s history of extensive skin lesions that started off as bullous lesions and biopsy revealed bullous pemphigus. Endoscopy for anemia revealed gastric cancer. This case reinforced the need to consider underlying malignancy in elderly patient with new onset dermatological presentation.     

Bullous pemphigoid after liver transplantation for liver failure.

Coomb's positive autoimmune hemolytic anemia with giant cell hepatitis (GCH) is a rare cause of liver failure and is usually associated with poor prognosis. A child with liver kidney microsomal (LKM) antibody positivity underwent successful liver transplantation for liver failure secondary to GCH with Coomb's positive hemolytic anemia. Autoimmune neutropenia developed ten months after transplant. Four months later, pemphigoid skin lesions developed. The diagnosis of bullous pemphigoid (BP) was made on the basis of skin biopsy, direct and indirect immunofluorescence test results. Treatment was with immunosuppressants - prednisone and azathioprine/rapamycin, with addition of dapsone when lesions persisted. This child is unique in that his liver function and hemolytic anemia appeared to normalize after liver transplant, but neutropenia and BP both thought to be autoimmune in etiology, developed more than a year post-transplant.     

Localized Bullous Pemphigoid Following Orthopedic Surgery

Bullous pemphigoid is an autoimmune condition whereby the immune system forms antibodies that target the skin, resulting in the formation of blisters in a generalized and symmetric pattern. Localized bullous pemphigoid can occur in special circumstances. Here, we describe two patients that developed localized bullous pemphigoid in one lower extremity following orthopedic surgery. We propose that underlying edema following orthopedic surgery is a potential trigger for localized bullous pemphigoid.     

Bullous pemphigoid-associated nephropathy: report of two cases and review of the literature

Bullous pemphigoid has previously been reported in association with a variety of renal lesions. Two additional cases are presented in this report in which the nephropathy preceded the onset of the skin disease: one case with membranous glomerulopathy and one case of renal allograft rejection with concurrent membranous pathology. Both patients had positive immunofluorescence of the skin, typical of bullous pemphigoid. Institution of systemic corticosteroid therapy resulted in a satisfactory clinical response and cessation of the blistering process. These cases and a review of the literature suggest that the occurrence of an immune process involving these two different basement membranes is not merely coincidental. Many cases have been described in which the severity of the skin lesions paralleled that of the renal disease. Although the possibility of multiple distinct autoimmune processes cannot be excluded, anti-basement-zone antibody interactions or allograft rejection-induced immune stimulation are possible unifying mechanisms for the simultaneous skin and renal involvement observed in these two cases.     

Linear IgA Bullous Dermatosis: A Rare Clinicopathologic Entity with an Unusual Presentation

Linear immunoglobulin A bullous dermatosis is a rare autoimmune mucocutaneous disorder caused by immunoglobulin A autoantibodies produced against several different antigens in the basement membrane zone. Clinically, it is characterized by tense vesicles or bullae, which on histopathological exam demonstrate subepidermal blister with a predominantly neutrophilic infiltrate. A smooth, linear pattern of immunoglobulin A deposition in the basement membrane zone on direct immunofluorescence is considered the gold standard for establishing a diagnosis. Treatment consists of dapsone or sulfapyridine. The authors report a 60-year-old woman who presented with pruritic erythematous patches and plaques on her trunk, back, and legs without blisters, who was diagnosed with eczema for several months with no response to prior treatments. A biopsy was performed, which was consistent with linear immunoglobulin A bullous dermatosis and later confirmed by direct immunofluorescence studies. The authors present this case to increase awareness of this rare disease, which could manifest in a nonclassical, nonblistering fashion.Linear immunoglobulin A (IgA) bullous dermatosis (LABD), also known in the literature as linear IgA dermatosis, linear IgA disease, IgA pemphigoid, and linear dermatitis herpetiformis, was first described by Bowen in 1901; however, it was not recognized as a distinct entity from dermatitis herpetiformis (DH) until 1979. LABD is a rare autoimmune vesiculobullous disease with an incidence of 0.2 to 2.3 cases per million-population per year. Epidemiologically, there is an unestablished predominance of race or sex.1,2LABD has two clinical variants. In children, the disease is better known as chronic bullous disease of childhood (CBDC) with an average presentation occurring around 4.5 years.3 In adults, two peaks are identified—teenage years and the sixties.1     

Rhabdomyolysis, acute renal failure, and multiple focal neuropathies after drinking alcohol soaked with centipede

Many Chinese like to drink alcohol soaked with creatures for promoting health. This study reports a 49-year-old male who presented with multiple focal neuropathies of the upper limbs, coagulopathy, erythematous swelling of the bilateral upper extremities and trunk with bullous skin lesions, and rhabdomyolysis associated with acute renal failure after drinking alcohol soaked with centipede. Soaking a centipede, Scolopendra subspinipes mutilans, in 53% alcohol, produced the wine. Supportive treatment was administered, and the skin lesions and renal failure improved with subsequent neurologic deficit during the week following initial presentation. Alcohol binge or immobilization was the likely cause of neuropathy, bullous skin lesions and rhabdomyolysis in the patient. However, there is a possibility that centipede venom also contributed to the illness in this patient.     

Rhabdomyolysis,Acute Renal Failure,and Multiple Focal Neuropathies After Drinking Alcohol Soaked with Centipede

Many Chinese like to drink alcohol soaked with creatures for promoting health. This study reports a 49‐year‐old male who presented with multiple focal neuropathies of the upper limbs, coagulopathy, erythematous swelling of the bilateral upper extremities and trunk with bullous skin lesions, and rhabdomyolysis associated with acute renal failure after drinking alcohol soaked with centipede. Soaking a centipede, Scolopendra subspinipes mutilans, in 53% alcohol, produced the wine. Supportive treatment was administered, and the skin lesions and renal failure improved with subsequent neurologic deficit during the week following initial presentation. Alcohol binge or immobilization was the likely cause of neuropathy, bullous skin lesions and rhabdomyolysis in the patient. However, there is a possibility that centipede venom also contributed to the illness in this patient.     

Hyper-IgE syndrome and autoimmunity in Mexican children

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by recurrent skin abscesses, recurrent pneumonia with pneumatocele formation, eczema, eosinophilia, and elevated levels of serum IgE. Patients with the autosomal recessive (AR) form of HIES appear to be prone to developing autoimmune diseases. We present two cases of HIES with autoimmune complications; one case was a product of a consanguineous marriage, the other one was a sporadic case. The first patient presented with recurrent episodes of erythema nodosum, warts, bronchiolitis obliterans and thrombocytopenia. The second patient developed glomerulonephritis resulting in endstage renal failure. She later developed malar rash, oral ulcers, cerebral infarcts with vasculitis and positive ANA, anti-dsDNA, and antiphospholipid antibodies. We discuss the dilemma in treating patients who present with both primary immunodeficiency and autoimmunity.     

Successful treatment of oral linear IgA disease using mycophenolate.

Linear IgA disease (LAD) is a rare acquired autoimmune bullous disorder, characterized by linear deposition of IgA along the dermoepidermal basement membrane zone. The clinical presentation of LAD consists of vesiculobullous lesions affecting the skin and mucosal surfaces. The present case report presents a rare presentation of this vesiculobullous disorder. Although more than 50% of LAD patients present with oral lesions, there are few reported cases of involvement of the mouth as the sole manifestation. A 79-year-old female presented with a sore mouth and erosions affecting the palate. The symptoms resolved following the provision of mycophenolate, an antiproliferative immunosuppressant which has not previously appeared to have been reported in the long-term successful management of linear IgA disease limited to the mouth. We found that mycophenolate is a useful adjunct to the successful treatment of oral linear IgA when the uses of other immunosuppressants are contraindicated.     

Clinical and immunopathologic findings in oral lichen planus pemphigoides.

Lichen planus pemphigoides (LPP) is a rare, acquired, immunobullous disorder of skin that occasionally involves oral mucous membranes. Clinical, histologic, and immunopathologic findings of the oral manifestations of LPP are described. Clinical features are lichenoid striae, erosions, and ulcerations involving gingiva and buccal mucosae. Histopathologic features are similar to those of ora lichen planus. Direct immunofluorescence demonstrates linear deposits of immunoglobulin G and complement component C3 along the basement membrane with fibrillar deposits of fibrin at the epithelial/lamina propria junction. Fluorescence overlay antigen mapping and laser scanning confocal microscopy of the biopsy specimen exhibits colocalization of in situ antibodies with beta4 integrin, a marker of the keratinocyte basal plasma membrane and upper lamina lucida, consistent with the location of the bullous pemphigoid antigens. This case report describes a case of LPP that presented exclusively as an oral condition. Lichen planus pemphigoides should be considered in the clinical differential diagnosis of vesiculoerosive oral mucosal diseases.     

Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases: Current evidence

Dipeptidyl peptidase-4 inhibitors (DPP-4i) have an important place in the management of type 2 diabetes. The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological functions. DPP-4 regulates several immune functions, including T-cell activation, macrophage function, and secretion of cytokines. Studies have reported an increase in autoimmune diseases like bullous pemphigoid, inflammatory bowel disease, and arthritis with DPP-4i use. The relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more clearly. Whether a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious issue. Nevertheless, a heightened awareness from the clinicians is required to identify and treat any such diseases. Through this review, we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.     

Zosteriform pemphigoid after zoster: Wolf's isotopic response

The Wolf isotopic response describes the occurrence of a new, unrelated disease that appears at the same location as a previously healed disease. The most common primary skin disorder of this phenomenon is herpes zoster and less frequently, herpes simplex. We report a case of 79‐year‐old woman who have bullous pemphigoid (BP) with dermatomal distribution that developed at the site of previously healed herpes zoster. Based on clinical, histological and immunofluorescence findings, the patient was diagnosed with localized BP in a site of prior herpes zoster. BP developing at the site of healed herpes zoster is the first reported case. Recognition of this phenomenon is important for correct clinicopathologic diagnosis and may improve our understanding of the underlying pathophysiologic processes.     

Bullous Appearance of Pilomatricoma

BACKGROUND: Pilomatricomas, which are usually solitary, firm to hard tumors that are covered by normal skin, rarely show a bullous appearance. OBJECTIVE: To discuss, through a case report, the clinical and histopathologic characteristics of bullous pilomatricomas. METHODS: A 15-year-old boy presented with a firm, well-defined tumor on his right arm that showed dark-blue discoloration and bullous formation over it. RESULTS: Excisional biopsy was performed, and histopathologic examination confirmed the diagnosis of bullous pilomatricoma. CONCLUSION: The presence of dilated lymphatics, also seen in our patient, is a common feature of bullous pilomatricomas.     

Linear glomerular IgG fixation in renal allografts: incidence and significance in Alport's syndrome

Twelve of 767 renal allograft recipients developed linear fixation of IgG along the glomerular basement membrane (GBM) by direct immunofluorescence technique. This was associated with linear fixation along the tubular basement membrane in 7 of them. Circulating anti-GBM antibodies were not detected by indirect immunofluorescence or radioimmunoassay in any patient whereas anti-TBM antibodies were found in 2 of 4 with linear TBM fixation. Among the 12 patients with linear GBM fixation, 5 had Alport's syndrome; the 7 others had various renal diseases, excluding anti-GBM nephritis. Among the 767 patients, 34 had Alport's syndrome or variants (i.e., 4.5%). The incidence of linear GBM fixation is much higher in Alport's syndrome than in other renal diseases. Linear GBM fixation was not clearly related to anti-GBM antibodies and was not accompanied by significant deterioration of graft function. These findings may be relevant, however, to the missing GBM antigen in Alport's syndrome.     

The spectrum of renal involvement in epidermolysis bullosa dystrophica hereditaria: report of two cases

Epidermolysis bullosa dystrophica Hallopeau-Siemens (EBDH) is one of the most severe inherited epidermolyses, a group of mechanobullous dermatological disorders. We observed two patients presenting with a severely multilating type of EBDH who developed biopsy-proven renal disease, which substantially altered the evolution and pathogenesis of their disease. In a boy, chronic postinfectious glomerulonephritis developed, most probably due to recurring superinfections of bullous skin lesions. He also experienced acute oliguric renal failure due to severe diarrhea during exacerbation of EBDH. A female patient developed a nephrotic syndrome due to secondary amyloidosis. Hypoalbuminemia caused further fluid losses through bullous skin lesions, aggravating intravascular hypovolemia and leading to rapid renal failure secondary to bilateral renal vein thrombosis. The study shows that, although rare, renal complications may alter the natural course of EBDH.     

Anaesthesia for children with junctional epidermolysis bullosa (letalis)

The anaesthetic management of two children with junctional epidermolysis bullosa, formerly called the letalis form, is described. Anaesthesia for children with this disease has not been described previously. Special precautions were taken to avoid mucosal injury and some customary monitoring devices were omitted. The previous anaesthetic literature, which discusses related but distinct forms of bullous skin diseases, is reviewed. The special concerns which relate to airway management in this disease are discussed.     

Myofibroblastic tumors involving bilateral adrenal glands and skin in a patient with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a heterogeneous form of primary immune deficiency characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome have an increased incidence of autoimmune diseases and malignancy. A patient with CVID in whom myofibroblastic tumors affecting both adrenal glands and skin is presented.