Pyoderma Gangrenosum with Positive Antinuclear Antibody , in the Absence of Systemic Association

Pyoderma gangrenosum is an uncommon neutrophilic dermatosis, seen on legs, and infrequently on hands and other anatomical sites. It is associated with systemic diseases in 50-70% of the cases. Antinuclear antibody (ANA) seropositivity has been reported in pyoderma gangrenosum associated with connective tissue disorders. However, there are very few case reports of pyoderma gangrenosum in patients of systemic lupus erythematosus, while we did not find any reports of ANA seropositivity in isolated pyoderma gangrenosum. Hence, we report this unique case of pyoderma gangrenosum with classical clinicohistopathology, positive ANA but no systemic association. As anticipated, our patient responded promptly to steroids.


Introduction
P yoderma gangrenosum (PG) is a rare necro zing, ulcera ve neutrophilic dermatosis. 1 It is usually associated with various systemic illnesses, but rarely described in associa on with systemic lupus erythematosus (SLE) or an nuclear an body (ANA) seroposi vity.We report this case of PG on sunexposed sites, with posi ve ANA and no internal disease.

Case Report
A 61 years old lady, presented to Dermatology OPD, with complaint of mul ple painful ulcers on dorsa of bilateral hands and feet for seven days.Ini ally, there were mul ple, asymptoma c, erythematous papules on hands and feet, that rapidly evolved into large ulcera ve plaques.Pa ent did not no ce any cons tu onal symptoms during progression of lesions.She had no prior history of trauma, insect bite, topical applica on or drug intake.There was no fever, joint pain, morning s ff ness, diarrhea, cons pa on, pain abdomen, blood in stool, weight loss or decreased appe te.Pa ent did not have oral ulcers, malar rash, hair loss, menstrual irregularity or headache.No systemic comorbidi es were elicited from history.She was a nonsmoker.
On examina on, pa ent was afebrile with normal vital signs (BP 100/60 mm of mercury, Pulse 84/m, RR 18/min).Cutaneous examina on revealed fi ve annular lesions on sun-exposed sites of hands and feet (Figure 1).Among them, only one lesion on right hand was vegeta ve.Others were ulcera ve plaques of varying sizes, with undermined edges, irregular border, containing hemorrhagic and necro c slough and a conspicuous edematous violaceous margin.Largest plaque had dimensions of 6×5 cm.Head to toe examina on and systemic fi ndings were normal.Pathergy test was nega ve.
Histopathology confi rmed our provisional diagnosis, showing epidermal intracorneal neutrophilic collec ons with areas of necrosis and extensive dermal neutrophilic infi ltrates with vasculopathy (Figure 2).
Oral steroids (prednisolone) was started upon admission.Normal saline and vaseline gauze dressing was done twice a day for 3 days.Skin lesions showed drama c improvement with steroids within 48 hours (Figure 3).Pa ent was kept on hydroxychloroqine as maintenance therapy.There was no relapse un l two months of discon nua on of therapy ( ll date).

Discussion
Pyoderma gangrenosum (PG) is a painful, noninfec ous, rapidly spreading, necro zing skin ulcera on, regarded as a spectrum of neutrophilic dermatosis. 1 It was fi rst described in 1908 by French dermatologist Brocq as "geometric phagedenism", and later Bruns ng et al renamed it as "pyoderma gangrenosum" as he believed that it occurred secondary to bacterial infec on. 2,3 is an uncommon reac ve phenomenon, with 3-10 new cases per million popula on yearly. 4It usually aff ects adults between 20-50 years and rarely children.Around 50-70% cases have systemic associa on, observed commonly with infl ammatory bowel disease, rheumatoid arthri s and hematologic malignancy.It is also seen in surgical wound sites and at sites of trauma, known as pathergy, which occurs in 25-30% of PG. 1,4 There are four clinical forms of PG described as ulcera ve, bullous, pustular and vegeta ve lesions.Various clinical subtypes have dis nct systemic associa on.It begins as infl ammatory papule, nodule or pustule, which swi ly develops into undermined ulcero-necrosis with characteris c violaceous border. 1 It heals with descrip ve cribiform "cigare e paperlike" scars. 5Lesions occur in leg in 70% cases, less common on face, neck, hands, trunks, breast, genitalia and rarely at extracutaneous ssues. 6,7We did not fi nd pyoderma gangrenosum reported on sun-exposed sites.

Histopathology of early lesion from advancing border
shows infl ammatory infi ltrates in dermis, with or without leukocytoclas c vasculi s.Ulcera on of the epidermis tends to be secondary to the dermal infl amma on.Older lesion with ulcera on shows neutrophilic infi ltrates in epidermis and dermis, without infec ous agents. 8Diff use dermal neutrophilic infi ltrates seen in PG, without vasculi s and granuloma, has been called "sea of neutrophils." 1 In 2004, Su WP et al proposed a diagnos c criterion of PG. 5 It encompassed characteris c clinical ulcer and histological fi ndings, in associa on with systemic illnesses, a er excluding other causes of cutaneous ulcera on.Resistance to an bio cs and surgical therapy and improvement with steroids is dis nc ve. 7n our pa ent, there were classical lesions of PG on sun-exposed sites, that responded eff ec vely to steroids.Diagnosis of PG was made a er exclusion of other causes of cutaneous ulcer.Seroposi vity for ANA without manifesta ons of SLE or any other systemic disease is unprecedented.
ANA is regarded as a marker of systemic autoimmune connec ve ssue disorder.Although it is highly (95%) sensi ve for SLE, it is not a specifi c marker.Posi ve predic ve value of ANA in SLE in 11-49% and much lower in other connec ve ssue disorders (CTD). 9On the other hand, ANA is also observed in 5% of healthy individuals. 10Likewise, although SLE is common among women of reproduc ve age group, pyoderma gangrenosum is a rare en ty.Associa on of PG and SLE is rela vely recent and sparse. 11Waldman MA et al reported an interes ng case where PG preceded onset of SLE by 8 years. 12This should be noted as PG might be a harbinger of chronic autoimmunity.At the other end of the fringe, pa ent with chronic SLE has developed PG lesions. 13Hence the temporal rela onship between two diseases has been variable.In our case scenario, presence of PG lesions in a female with ANA reac vity suggests possibility of connec ve ssue disorder in future.However, since ANA is also observed in healthy individuals, and this fi nding could be coincidental in isolated PG.With further studies, the associa on of SLE and ANA with PG might be extrapolated in future.
The mainstay of treatment is steroids, although there associa on, we have described this en ty.We did not fi nd any evidence of connec ve ssue disorder in our pa ent, but have discussed previous associa ons.Further studies might validate the rela on of PG with SLE, as well as its dynamics with ANA serology.
Financial disclosure: None.Confl icts of interest to disclosure: None declared.

Conclusion
Given the rarity of pyoderma gangrenosum, and no previous reports of ANA reac vity without systemic

Figure 1 :
Figure 1: Large ulceronecro c lesions with edematous violaceous border on dorsa of hands and feet.Single vegeta ve lesion on dorsum of right hand

Figure 3 :
Figure 3: Clinical improvement on Day 2 and Day 4 of star ng treatment.