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CASE REPORT Table of Contents  
Ahead of print publication
Pyoderma gangrenosum in systemic lupus erythematosus: An uncommon association


 Department of General Medicine, Government Medical College and Hospital, Chandigarh, India

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Date of Submission01-Dec-2021
Date of Decision26-Jan-2022
Date of Acceptance02-Feb-2022
Date of Web Publication12-Feb-2022
 

  Abstract 


Pyoderma gangrenosum (PG) is a type of neutrophilic diseases and is an uncommon, idiopathic, ulcerative dermatosis. On the contrary, systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem, progressive disease that causes widespread inflammation in joints, skin, blood vessels, and several other organs. The rash of SLE is usually on photo-distributed areas, especially the face. PG-like ulceration was previously reported with antiphospholipid antibody syndrome; however, the association of PG and SLE is rarely observed. We report a rare manifestation of SLE presenting as ulcerative PG in a 46-year-old female who was diagnosed with SLE with no evidence of inflammatory bowel disease, rheumatoid arthritis, chronic active hepatitis, monoclonal gammopathies, and hematological malignancies. She developed a skin lesion on her right breast region which was later diagnosed to be PG following biopsy and was managed with corticosteroids and appropriate wound management.

Keywords: Breast, neutrophilic dermatoses, pyoderma gangrenosum, skin lesion, systemic lupus erythematosus


How to cite this URL:
Gupta H, Kaur J, Kaur D. Pyoderma gangrenosum in systemic lupus erythematosus: An uncommon association. Apollo Med [Epub ahead of print] [cited 2022 Sep 27]. Available from: https://apollomedicine.org/preprintarticle.asp?id=337616





  Introduction Top


Neutrophilic diseases (NDs) represent a diverse group of conditions involving various body organs and sharing clinical and pathological features with autoinflammatory syndromes.[1]

Pyoderma gangrenosum (PG), a type of ND, is usually associated with multiple systemic disorders[2],[3],[4] and manifested by distinct erythematous to violaceous undermined border which extends the ulcer bed.[5],[6],[7]

Lupus patients may develop ulcerative skin lesions on leg that are usually due to vasculitis, thrombophilic state, or antiphospholipid antibodies.[7] The association of PG and systemic lupus erythematosus (SLE) has been rarely reported. This case report describes PG in a patient with SLE – an unusual association. The location of the lesion is unusual.


  Case Report Top


Patient information

A 46-year-old female patient from Chandigarh (India) presented in 2018 with a complaint of a painful pustular lesion on the right side of the breast which apparently appeared almost a month ago. The patient had a past medical history of SLE with autoimmune hemolytic anemia, neuropsychiatric manifestations diagnosed in 2017 for which hydroxychloroquine (HCQ) 200 mg and oral prednisolone 5 mg per day were prescribed for the past 1 year.

Clinical findings

Physical examination revealed a slightly asymmetric enlarged right breast and a painful pustular lesion with surrounding inflammation and erythema. There was no history of any trauma, discharge, or any feeling of a lump. Furthermore, the patient denied any history of breast surgery or family history of the tumor. Vital signs were within normal limits except for the raised temperature.

Diagnostic assessment

At the time of presentation in 2018, the patient had fever and multiple abnormal body movements with a painful lesion on the right breast [Figure 1]. Fundus examination ruled out any disk edema/vasculitis and cerebrospinal fluid (CSF) examination showed acellular, protein 61, glucose 12, and adenosine deaminase ADA 12. The patient required multiple blood transfusions, and intravenous (iv) antiepileptics were given for generalized tonic-clonic seizures (GTCS).
Figure 1: Skin lesion over the right breast of the patient

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Clinical/laboratory findings of the patient confirmed pancytopenia (indirect Coombs test negative), positive antinuclear antibody (ANA) test (ANA + 4), positive anti-double-stranded DNA test, and low complement levels, C3 (31.9 vs. 90–180) and C4 (7.53 vs. 9–36). Erythrocyte sedimentation rate and C-reactive protein were found to be slightly elevated. Furthermore, blood culture and swab culture from the lesion did not show any microbial growth; however, urine culture showed the presence of Escherichia coli sensitive to amikacin and colistin. Electroencephalogram suggested an abnormal sleep cycle, and contrast-enhanced magnetic resonance imaging ruled out any parenchymal abnormality. CSF picture was found to be grossly normal. Thyroid peroxidase antibodies (anti-TPO) and thyroid profile were normal.

Differential diagnosis

Differential diagnoses of cutaneous tuberculosis, vasculitis, and antiphospholipid antibody syndrome were kept.

Therapeutic intervention

A punch biopsy of the right breast lesion was also performed which indicated PG with neutrophilic involvement of deep dermis [Figure 2]. Sigmoidoscopy ruled out any evidence of inflammatory bowel disease (IBD).
Figure 2: Punch biopsy from a skin lesion (right breast): Deeper dermis and the subcutaneous tissues show marked inflammatory infiltrate involving both the septa and lobules of the subcutaneous fat. Findings were consistent with pyoderma gangrenosum

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Later to this, the patient developed hospital-acquired pneumonia (HAP) along with progressive worsening of neuropsychiatric manifestation in the form of seizures and abnormal behavior.

Multiple blood transfusions were given to the patient at the time of admission. iv antiepileptics were initiated immediately, considering the development of GTCS. Her urine sample showed E. coli infection for which she was treated with iv antibiotics initially; however, pertaining to no improvement in the ulcer with broad-spectrum iv antibiotics and steroids, a dermatologist was consulted, and topical corticosteroids were added in the therapy. PG was managed with iv pulse therapy of methylprednisone followed by 40 mg oral prednisolone and 200 mg HCQ.

Follow-up and outcomes

The patient was initially started on prednisolone and HCQ along with an iv antibiotic. Later, there was progressive worsening in neuropsychiatric manifestations of SLE in the form of seizures and behavioral abnormalities. The patient developed HAP and succumbed to her illness after 32 days of admission.


  Discussion Top


SLE is a chronic, autoimmune, multisystem, progressive disease manifested by the presence of numerous autoantibodies and formation of immune complexes causing widespread inflammation in joints, skin, blood vessels, and several other organs such as brain, lungs, and kidneys. SLE can range from mild to life-threatening conditions.[7],[8]

Although PG-like ulceration was earlier noted in few cases of antiphospholipid antibody syndrome,[9],[10],[11],[12] PG is a rare disease with unclear pathogenesis and may epitomize a prototype of cutaneous autoinflammatory disorder. The occurrence of PG and SLE together is a rare phenomenon, unlike with IBD, arthritis, and hematologic malignancies. PG may be seen along with, following, or preceding certain systemic disorders. PG is seen equally in both the sexes, with the peak incidence seen between 20 and 50 years of age.[1],[3]

Even though Su et al.[13] have reported diagnostic criteria for PG, it is not yet recognized for clinical use, and thus, PG still remains a diagnosis of exclusion. PG has a characteristic clinical presentation, but it appears similar to few other ulcerating conditions leading to a high probability of misdiagnosis. The major concerns with diagnostic evaluation are exclusion of infection and investigation of an underlying disease. Differential diagnosis of PG must be done with several other conditions, as mentioned in [Table 1].[13],[14]
Table 1: Differential diagnosis of pyoderma gangrenosum[13],[14]

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Although there are no specific histopathological findings seen in PG, the below-mentioned differential diagnosis must always be ruled out by performing a skin biopsy as done in our patient. A clear analysis must be made for SLE patients to rule out the association of PG with primary and secondary antiphospholipid syndrome and aPL antibodies.[15],[16]

The underlying reason for the inflammatory response seen in PG is still not known, but in a study done by Adachi et al.,[17] it was seen that there is an abnormality of the underlying neutrophil trafficking system seen in patients with PG. The response of toll-like receptors has also been reported to be increased in the skin lesions of the patients.[18] Another mechanism seen in the pathogenesis of SLE is an imbalance between the production and clearance of neutrophil extracellular traps, leading to a vicious cycle of tolerance breakage and autoimmunity, further leading to the unforeseen occurrence of the two diseases together.[19]

The response of the patients with steroids and other immunosuppressive therapy often adds another pointer toward the underlying autoimmune etiology of the disease. The association between SLE and PG is rare; consequently, the therapeutic management is challenging due to lack of specificity and so, a high index of clinical judgment is necessary. The absence of thrombi, vasculitis in the vessels, and cutaneous infections can point toward PG. Prompt institution of appropriate treatment strategies is important to achieve a successful outcome. We recommend that PG should be considered while evaluating painful skin ulcers in SLE patients; however, the presence of common disorders such as skin infection or vascular disease must be ruled out beforehand.


  Conclusion Top


  • Skin involvement occurs in 80% of the patients with SLE at some point of the disease and can yield valuable diagnostic (LE specific lesions) as well as prognostic (LE nonspecific lesions) information
  • PG and other NDs reported in SLE patients may be added to the large clinical spectrum of neutrophilic cutaneous lupus erythematosus lesions, and for this reason, more knowledge exchange between rheumatologists and dermatologists will lead to a specific diagnosis of cutaneous manifestations in patients with SLE
  • A strong clinical judgment and prompt institution of therapy is very much needed for a successful outcome
  • Management by a multidisciplinary team is the need of the hour for accurate diagnosis and therapeutic management of rare infections.


Declaration of the patient consent form

Written patient consent is present, duly signed by the patient. The authors obtained the consent after explaining that no identity will be revealed, and the case information, including pictures, will be used for education purposes only. She was also explained that journal publication will not contain any material or picture disclosing her identity. The patient gave positive consent for publication, and the authors certify that written patient consent is present, procured for publication.

Informed consent

Proper written consent is present, which was obtained from the patient for the use of the data related to this case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Marzano AV, Borghi A, Wallach D, Cugno M. A comprehensive review of neutrophilic diseases. Clin Rev Allergy Immunol 2018;54:114-30.  Back to cited text no. 1
    
2.
Soutou B, Vignon-Pennamen D, Chosidow O. Neutrophilic dermatoses. Rev Med Interne 2011;32:306-13.  Back to cited text no. 2
    
3.
Langan SM, Groves RW, Card TR, Gulliford MC. Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: A retrospective cohort study. J Invest Dermatol 2012;132:2166-70.  Back to cited text no. 3
    
4.
Lebrun D, Robbins A, Hentzien M, Toquet S, Plee J, Durlach A, et al. Two case reports of pyoderma gangrenosum and systemic lupus erythematosus: A rare but nonfortuitous association? Medicine (Baltimore) 2018;97:e11933.  Back to cited text no. 4
    
5.
Callen JP. Pyoderma gangrenosum. Lancet 1998;351:581-5.  Back to cited text no. 5
    
6.
Powell FC, Schroeter AL, Su WP, Perry HO. Pyoderma gangrenosum: A review of 86 patients. Q J Med 1985;217:173-86.  Back to cited text no. 6
    
7.
Waldman MA, Callen JP. Pyoderma gangrenosum preceding the diagnosis of systemic lupus erythematosus. Dermatology 2005;210:64-7.  Back to cited text no. 7
    
8.
Gurevitz SL, Snyder JA, Wessel EK, Frey J, Williamson BA. Systemic lupus erythematosus: A review of the disease and treatment options. Consult Pharm 2013;28:110-21.  Back to cited text no. 8
    
9.
Hostetler LW, von Feldt J, Werth VP. Cutaneous ulcers in a patient with systemic lupus erythematosus. Arthritis Rheum 1993;36:91-3.  Back to cited text no. 9
    
10.
Schlesinger IH, Farber GA. Cutaneous ulceration resembling pyoderma gangrenosum in the primary antiphospholipid syndrome: A report of two additional cases and review of the literature. J La State Med Soc 1995;147:357-61.  Back to cited text no. 10
    
11.
Olson K. Pyoderma gangrenosum with systemic LE. Acta Derm Venereol (Stockh) 1971;51:233-4.  Back to cited text no. 11
    
12.
Babe KS Jr., Gross AS, Leyva WH, King LE Jr. Pyoderma gangrenosum associated with antiphospholipid antibodies. Int J Dermatol 1992;31:588-90.  Back to cited text no. 12
    
13.
Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: Clinicopathologic correlation and proposed diagnostic criteria. Int J Dermatol 2004;43:790-800.  Back to cited text no. 13
    
14.
Callen JP. Neutrophilic dermatoses. Dermatol Clin 2002;20:409-19.  Back to cited text no. 14
    
15.
Cañas CA, Durán CE, Bravo JC, Castaño DE, Tobón GJ. Leg ulcers in the antiphospholipid syndrome may be considered as a form of pyoderma gangrenosum and they respond favorably to treatment with immunosuppression and anticoagulation. Rheumatol Int 2010;30:1253-7.  Back to cited text no. 15
    
16.
Stephansson EA, Niemi KM, Jouhikainen T, Vaarala O, Palosuo T. Lupus anticoagulant and the skin. A longterm follow-up study of SLE patients with special reference to histopathological findings. Acta Derm Venereol 1991;71:416-22.  Back to cited text no. 16
    
17.
Adachi Y, Kindzelskii AL, Cookingham G, Shaya S, Moore EC, Todd RF 3rd, et al. Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma gangrenosum. J Invest Dermatol 1998;111:259-68.  Back to cited text no. 17
    
18.
Ortega-Loayza AG, Nugent WH, Lucero OM, Washington SL, Nunley JR, Walsh SW. Dysregulation of inflammatory gene expression in lesional and non-lesional skin of patients with pyoderma gangrenosum. Br J Dermatol 2018;178:35-6.  Back to cited text no. 18
    
19.
Leffler J, Gullstrand B, Jönsen A, Nilsson JÅ, Martin M, Blom AM, et al. Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus. Arthritis Res Ther 2013;15:R84.  Back to cited text no. 19
    

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Correspondence Address:
Jaspreet Kaur,
Department of General Medicine, Government Medical College and Hospital, Sector 32, Chandigarh - 160 030
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_139_21



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