History
A 13-year-old girl presented with a 3-month history of intermittent, tender, draining lesions on her trunk, and upper and lower extremities. Physical examination demonstrated several well defined, pink, indurated tender plaques (Fig 1). The patient was treated for a presumed superficial skin/soft tissue infection with intravenous vancomycin and meropenem. Findings recurred after transitioning to oral antibiotics. A total of 4 mm punch biopsies obtained from bilateral thighs, and right shoulder lesions demonstrated lobular neutrophilic panniculitis without vasculitis (Fig 2, A, B). Wound and tissue cultures showed no significant growth. Workup to determine the underlying cause of panniculitis revealed low levels of α-1 antitrypsin.
Question 1: What is the most likely diagnosis?
-
A.
Subcutaneous Sweets syndrome
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B.
α-1 antitrypsin deficiency (AATD) panniculitis
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C.
Infection
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D.
Erythema nodosum
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E.
Pancreatic panniculitis
Answers:
-
A.
Subcutaneous Sweets syndrome – Incorrect. Although histologically Sweets syndrome is defined as a neutrophilic panniculitis with inflammatory infiltrate and fat necrosis,1 the decreased levels of α-1 antitrypsin is not present in this condition.
-
B.
α-1 antitrypsin deficiency (AATD) panniculitis – Correct. Panniculitis is a rare but reported manifestation of AATD. Decreased serum levels of α-1 antitrypsin lead to the diagnosis of AATD. Although this is a rare manifestation of AATD there numerous cases reported in the literature.2
-
C.
Infection – Incorrect. The multiple negative tissue and wound cultures obtained from this patient decrease the likelihood of an infectious cause of the panniculitis. Additionally, histology from an infectious panniculitis has evidence of basophilic debris and vascular damage,1 not seen in this patient.
-
D.
Erythema nodosum – Incorrect. Erythema nodosum is described as lymphocytic or granulomatous panniculitis.1 In very early stages there is more neutrophilic component to the histology, however, with more septation present,1 which was not found on this patient.
-
E.
Pancreatic panniculitis – Incorrect. Although pancreatic panniculitis is a form of neutrophilic panniculitis, histology usually presents with “ghost cells,” which are the necrotic adipocytes that have turned blue-gray due saponification and dystrophic calcification.1 Additionally pancreatic panniculitis is associated with acute or chronic pancreatitis, which was not observed in this patient.
Question 2: What is the most common first-line treatment?
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A.
Glucocorticoids
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B.
IV α-1 antitrypsin protein replacement
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C.
Dapsone
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D.
Doxycycline
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E.
Immunosuppression
Answers:
-
A.
Glucocorticoids – Incorrect. Glucocorticoids were initially trialed for treatment for AATD panniculitis and in the systemic treatment was unable to provide complete resolution.3
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B.
IV α-1 antitrypsin protein replacement – Incorrect. IV α-1 antitrypsin is not often used for the first-line treatment for AATD panniculitis because of the high cost and the increased risk that is associated with blood products.3
-
C.
Dapsone – Correct. Dapsone is the most common first-line treatment for AATD panniculitis that is sited in the literature.3 The benefits of dapsone include the antineutrophilic properties. However, before treatment with dapsone can begin patient must first be screened for glucose-6-phosphate dehydrogenase deficiency, as it is a contraindication.
-
D.
Doxycycline – Incorrect. Treatment with tetracyclines, such as doxycycline, have had some use with decreasing the inflammatory response, treatment with doxycycline alone has failed to produce a satisfying result, and is often used alongside the first-line treatment.3
-
E.
Immunosuppression – Incorrect. Similarly, to doxycycline immunosuppressants showed an anti-inflammatory response but has not shown to produce a satisfying result as a singular therapy.3
Question 3: Which of the following is not another clinical manifestation of AATD
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A.
Emphysema
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B.
Liver disease
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C.
Vasculitis
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D.
Pancreatitis
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E.
Hair loss
Answers:
-
A.
Emphysema – Incorrect. One of the most common clinical manifestations of AATD is emphysema due to the unopposed proteolytic destruction in the lung.2
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B.
Liver disease – Incorrect. Liver disease is a result of the accumulation of misfolded α-1 antitrypsin protein in the liver parenchyma.2
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C.
Vasculitis – Incorrect. Vasculitis does not occur as frequently but has been reported. AATD vasculitis has been associated with cytoplasmic anti-neutrophil cytoplasmic antibody positive vasculitis.2
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D.
Pancreatitis – Incorrect. Pancreatitis has been associated with the mutation of the Z allele genotype of AATD.2
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E.
Hair loss – Correct. There has been not evidence in the literature of hair loss associated with AATD.
Conflicts of interest
None disclosed.
Footnotes
Funding sources: None.
Patient consent: The authors attest that they have obtained written consent from patient/s, their legal guardian/s or person/s with legal authority, for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but are retained by the authors to be made available upon request.
IRB approval status: Not applicable.
References
- 1.Chan M.P. Neutrophilic panniculitis: algorithmic approach to a heterogeneous group of disorders. Arch Pathol Lab Med. 2014;138(10):1337–1343. doi: 10.5858/arpa.2014-0270-CC. [DOI] [PubMed] [Google Scholar]
- 2.Kelly E., Greene C.M., Carroll T.P., McElvaney N.G., O’Neill S.J. Alpha-1 antitrypsin deficiency. Respir Med. 2010;104(6):763–772. doi: 10.1016/j.rmed.2010.01.016. [DOI] [PubMed] [Google Scholar]
- 3.Franciosi A.N., Ralph J., O’Farrell N.J., et al. Alpha-1 antitrypsin deficiency-associated panniculitis. J Am Acad Dermatol. 2022;87(4):825–832. doi: 10.1016/j.jaad.2021.01.074. [DOI] [PubMed] [Google Scholar]