Pediatric Annals

Case Challenge: Rheumatology 

A 6-Year-Old Girl with Extensive Bullous Skin Lesions

Caroline Rassbach, MD; Neha Shah, MD; Aisha Davis, MD

Abstract

Physical examination on admission revealed a nontoxic-appearing girl with extensive fluid-filled bullous lesions of varying sizes behind her ears, around her eyes and mouth, and on her neck, trunk, back, axillae, and perineum (Figures 1 and 2). Mucous membrane involvement included small bullae in her nares, hard palate, and perianal region. She had scattered bullae on her wrists and ankles, although her extremities were relatively spared. The skin at the base of the bullae was erythematous, slightly raised, and pruritic.

Figure 1. Extensive fluid-filled bullous lesions of varying sizes covering the mouth, neck, and trunk of a 6-year-old girl.All images courtesy of Neha Shah, MD, MPH. Reprinted with permission.

Figure 2. Extensive fluid-filled bullous lesions of varying sizes covering the trunk and perineum of a 6-year-old girl.

Initial work-up included a normal complete blood count and electrolytes, clear chest radiograph, and negative herpes simplex virus antigen swab from one of her lesions. She was admitted to the hospital for wound care, pain control, nutritional support, and diagnostic evaluation. She continued to develop bullae during her initial hospital days until approximately 60% of her TBSA was affected (Figure 3). Her palms and soles also developed lesions. Further testing and a skin biopsy revealed the diagnosis.

Figure 3. Lesions on the palm of the hand of a 6-year old girl.

 

Bullous Systemic Lupus Erythematosus

The patient’s antinuclear antibody was positive with a titer of 1:640. The skin biopsy revealed a dense, primarily neutrophilic infiltrate and separation at the dermal-epidermal junction. Direct immunofluorescence revealed basement membrane deposits of immunoglobulin G (IgG), IgA, and IgM without complement deposits. This pattern is consistent with bullous pemphigoid, epidermolysis bullosa acquisita, or bullous systemic lupus erythematosus (BSLE). Additional serologic studies supported the diagnosis of BSLE, including positive anti-DNA antibodies, anti-Smith antibodies and anti-RNP antibodies, and low C3 and C4 levels. Serum testing for bullous pemphigoid-specific antibodies was negative.

To our knowledge, our 6-year-old patient is the youngest reported case of BSLE in the literature. BSLE occurs most commonly in females between the ages of 10 and 40 years, with the youngest previously reported case in an 8-year-old girl.

Bullous systemic lupus erythematosus is a vesiculobullous eruption that may include vesicles or bullae on an erythematous base filled with serous or serosanguinous fluid. The lesions are generalized, often symmetric, and may involve the mucous membranes. Commonly affected areas include the skin over the joints, sun-exposed regions, the trunk, and the vermilion border. Lesions typically rupture and then crust over, eventually healing as non-scarred hyper- or hypo-pigmented patches. Patients with BSLE may develop chronic vesicobullous lesions or may show spontaneous resolution after 1 to 2 years.

Patients with BSLE represent fewer than 5% of all patients with systemic lupus erythematosus (SLE) and may or may not have other skin and systemic manifestations of SLE. Nephritis is the most common systemic manifestation in patients with BSLE. BSLE has been reported as the initial presentation of SLE, as coinciding with an SLE exacerbation, and also following initiation of treatment for an SLE flare. Diagnostic criteria for BSLE include the presence of acquired, non-scarring vesicles or bullae, meeting the American College of Rheumatology criteria for SLE, and characteristic histopathology and immunofluorescence testing. The skin biopsy in BSLE reveals subepidermal neutrophilic infiltration in a concentrated or continuous pattern. Direct immunofluorescence testing reveals IgG in a linear or granular pattern at the dermo-epidermal junction. Antibodies to type VII collagen of the dermal floor may also be present. This infiltration leads to the characteristic separation of the dermis and epidermis, resulting in vesiculobullous lesions.

The differential diagnosis for a child with a bullous skin…

A 6-year-old previously healthy girl presented with extensive bullous skin lesions involving approximately 25% of her total body surface area (TBSA). She initially presented 9 days earlier with low-grade fever, bilateral non-exudative conjunctival injection, cough, and rash. Her rash appeared as raised, erythematous target lesions that began behind her ears and then progressed to involve her face and body. Her symptoms at first presentation were attributed to erythema multiforme and she was treated with hydroxyzine and olopatadine eye drops. Five days later, fluid-filled bullae developed at the centers of the target lesions and increased in number and size up to the time of admission.

Physical examination on admission revealed a nontoxic-appearing girl with extensive fluid-filled bullous lesions of varying sizes behind her ears, around her eyes and mouth, and on her neck, trunk, back, axillae, and perineum (Figures 1 and 2). Mucous membrane involvement included small bullae in her nares, hard palate, and perianal region. She had scattered bullae on her wrists and ankles, although her extremities were relatively spared. The skin at the base of the bullae was erythematous, slightly raised, and pruritic.

Extensive fluid-filled bullous lesions of varying sizes covering the mouth, neck, and trunk of a 6-year-old girl.All images courtesy of Neha Shah, MD, MPH. Reprinted with permission.

Figure 1. Extensive fluid-filled bullous lesions of varying sizes covering the mouth, neck, and trunk of a 6-year-old girl.All images courtesy of Neha Shah, MD, MPH. Reprinted with permission.

Extensive fluid-filled bullous lesions of varying sizes covering the trunk and perineum of a 6-year-old girl.

Figure 2. Extensive fluid-filled bullous lesions of varying sizes covering the trunk and perineum of a 6-year-old girl.

Initial work-up included a normal complete blood count and electrolytes, clear chest radiograph, and negative herpes simplex virus antigen swab from one of her lesions. She was admitted to the hospital for wound care, pain control, nutritional support, and diagnostic evaluation. She continued to develop bullae during her initial hospital days until approximately 60% of her TBSA was affected (Figure 3). Her palms and soles also developed lesions. Further testing and a skin biopsy revealed the diagnosis.

Lesions on the palm of the hand of a 6-year old girl.

Figure 3. Lesions on the palm of the hand of a 6-year old girl.

 

Diagnosis:

Bullous Systemic Lupus Erythematosus

The patient’s antinuclear antibody was positive with a titer of 1:640. The skin biopsy revealed a dense, primarily neutrophilic infiltrate and separation at the dermal-epidermal junction. Direct immunofluorescence revealed basement membrane deposits of immunoglobulin G (IgG), IgA, and IgM without complement deposits. This pattern is consistent with bullous pemphigoid, epidermolysis bullosa acquisita, or bullous systemic lupus erythematosus (BSLE). Additional serologic studies supported the diagnosis of BSLE, including positive anti-DNA antibodies, anti-Smith antibodies and anti-RNP antibodies, and low C3 and C4 levels. Serum testing for bullous pemphigoid-specific antibodies was negative.

Discussion

To our knowledge, our 6-year-old patient is the youngest reported case of BSLE in the literature. BSLE occurs most commonly in females between the ages of 10 and 40 years, with the youngest previously reported case in an 8-year-old girl.

Bullous systemic lupus erythematosus is a vesiculobullous eruption that may include vesicles or bullae on an erythematous base filled with serous or serosanguinous fluid. The lesions are generalized, often symmetric, and may involve the mucous membranes. Commonly affected areas include the skin over the joints, sun-exposed regions, the trunk, and the vermilion border. Lesions typically rupture and then crust over, eventually healing as non-scarred hyper- or hypo-pigmented patches. Patients with BSLE may develop chronic vesicobullous lesions or may show spontaneous resolution after 1 to 2 years.

Patients with BSLE represent fewer than 5% of all patients with systemic lupus erythematosus (SLE) and may or may not have other skin and systemic manifestations of SLE. Nephritis is the most common systemic manifestation in patients with BSLE. BSLE has been reported as the initial presentation of SLE, as coinciding with an SLE exacerbation, and also following initiation of treatment for an SLE flare. Diagnostic criteria for BSLE include the presence of acquired, non-scarring vesicles or bullae, meeting the American College of Rheumatology criteria for SLE, and characteristic histopathology and immunofluorescence testing. The skin biopsy in BSLE reveals subepidermal neutrophilic infiltration in a concentrated or continuous pattern. Direct immunofluorescence testing reveals IgG in a linear or granular pattern at the dermo-epidermal junction. Antibodies to type VII collagen of the dermal floor may also be present. This infiltration leads to the characteristic separation of the dermis and epidermis, resulting in vesiculobullous lesions.

The differential diagnosis for a child with a bullous skin eruption includes bullous erythema multiforme, Stevens Johnson syndrome/toxic epidermal necrolysis, epidermolysis bullosa acquisita, chronic bullous disease of childhood (CBDB), bullous pemphigoid, and pemphigus vulgaris. These diagnoses are made based on clinical presentation and skin biopsy results.

Bullous SLE is often responsive to dapsone, which may be due to this medication’s ability to impair neutrophils and prostaglandins. Additional treatment options include immune modulators such as colchicine, azathioprine, antimalarials, cyclophosphamide, methotrexate, and mycophenolate mofetil. The skin lesions of BSLE may be unresponsive to steroids, but steroids are still used when other systemic manifestations of SLE are present. Treatment of BSLE should be guided by a rheumatologist.

During our patient’s hospital course, the bullae enlarged and then ruptured, leaving tender, denuded areas that quickly epithelialized. They healed without scarring but with residual hypopigmentation. The patient continued to develop new bullous lesions that involved her extremities, palms, and soles. She also developed signs of nephritis, including proteinuria, anemia, and hypoalbuminemia. As a result, she was started on a regimen of high-dose methylprednisolone, mycophenolate mofetil, and hydroxychloroquine in order to suppress her lupus activity. Despite these immunosuppressives, she continued to develop new bullae over a period of many weeks, requiring a prolonged hospital stay and treatment with two doses of intravenous immunoglobulin (IVIG), dapsone, and rituximab.

The patient’s hospital course was complicated by fever, edema, and tachycardia. Her care required a multidisciplinary approach including fluid management, nutritional support, pain control, wound care, and immunosuppressive therapy. The patient’s edema and tachycardia were managed with multiple infusions of albumin followed by furosemide. She required a transfusion of packed red blood cells and a peripherally inserted central catheter to maintain access. Due to the necessity for optimal protein status for wound healing, nutrition was supported with nasogastric tube feeds. Her pain was managed with opioids, gabapentin, and a low-dose ketamine drip guided by pain management consultants. Fevers were treated empirically with clindamycin for coverage of skin flora, including possible methicillin-resistant Staphylococcus aureus (MRSA). Blood, urine, and wound cultures failed to show a source of infection. She ultimately was treated for cellulitis that developed on her foot near the site of several of her lesions.

The most challenging aspect of her care was wound management, as there were limitations in mobility and positioning given the extensive nature of her bullae. In general, small bullae were left intact to allow a natural bandage and sterile environment. These bullae eventually ruptured spontaneously, healed within 1 to 2 days, and left hypopigmented skin behind. Larger bullae were ruptured manually due to pain and interference with positioning and ambulation. Healing patterns were similar for these bullae. Her wound care was performed daily under the guidance of an advance practice wound care nurse.

Following an 8-week hospitalization, the patient demonstrated significant healing of her skin and a decrease in the development of new bullous lesions. A slow steroid taper was begun, and she was discharged home on mycophenolate mofetil, hydroxychloroquine, and dapsone.

Conclusion

Although extremely rare in children, bullous systemic lupus erythematosus should be considered in the differential diagnosis for any child with vesiculobullous disease, and appropriate serologic testing for autoimmune markers and skin biopsy should be considered in these patients.

References

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Authors

Caroline Rassbach, MD, is a Pediatric Hospitalist at Lucile Packard Children’s Hospital, Palo Alto, CA. Neha Shah, MD, is a Pediatric Hospitalist at Children’s National Medical Center, Washington, DC. Aisha Davis, MD, is a Pediatric Hospitalist at Children’s National Medical Center, Washington, DC.

Disclosure: The authors have disclosed no relevant financial relationships.

Address correspondence to: Caroline Rassbach, MD, 770 Welch Road #100, Palo Alto, CA 94304; fax 650-498-5684; email: crassbac@stanford.edu.

Editor’s Note:

Each month, Case Challenge features an unusual diagnosis. A description and images are presented, followed by the diagnosis and an explanation of how the diagnosis was determined. Your comments are welcome via email at Pediatrics@Healio.com. To submit a case, visit: www.Healio.com/PedAnnals/Submit.

10.3928/00904481-20120525-05

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