When The Cart Is Before The Horses - Pyoderma Gangrenosum As Preceding Idiopathic Ulcerative Colitis: First Report in Gambia

Chronic inflammatory bowel disease is characterized by a plethora of intestinal and extra-intestinal manifestations, and it is not difficult to establish its diagnosis when all the elements are present; however, when the extra-intestinal manifestations precede and are more severe than the intestinal symptoms themselves, then it becomes a diagnostic challenge, delaying treatment, affecting quality of life, and darkening its prognosis. We report a case with six-months onset of necrotic ulcerative lesions, compatible with severe pyoderma gangrenosum, as the first and only manifestation of the disease during first four months, with only and vague symptoms of intestinal manifestations such as abdominal pain, and diarrhea with phlegm and rarely with blood last two months. Diagnosis of ulcerative colitis was established through colonoscopy, with the biopsy being non-specific in the diagnosis of colitis. The response of the dermatological manifestations was spectacular to conventional therapy with steroids and salicylates.


İntroduction
26-year-old woman, married with three children, previously healthy.Six months ago, she began to present skin lesions on his upper and lower limbs, which quickly turned septic and painful.Some were partially cured, but others persisted, even getting worse.During this period, she has lost 7 kg of weight, loss of appetite, tiredness and diffuse hair loss which has turned dry.In the last two months, she has been presenting intermittent episodes of diarrhea with phlegm, and a few times with traces of blood, for which he has received recurrent treatments with ciprofloxacin and metronidazole without real improvement.
On physical examination, appears chronically ill, with marked weight loss.Purulent wounds, with dirty fundus, active bleeding, irregular edges, and of variable sizes, some greater than 3 cm in diameter, involving upper and lower extremities (Figures 1 and 2).
Oral and ocular mucosa appear pale, aside from previously described skin lesions, the rest of the physical examination was negative.

Discussion
Pyoderma gangrenosum (PG) first described by Brunsting, Goeckerman and O'Leary in 1930 Initially, mistakenly believed that its cause was infectious, which is why was called "pyoderma" [1].Universally is consider as autoinflammatory non-infectious neutrophilic dermatosis and includes Sweet's syndrome and Behcet's syndrome [2][3][4] characterized by recurrent skin ulcers with mucopurulent or hemorrhagic exudate, which can be reactive or associated in 50% of cases to multiple systemic diseases.PG has an annual incidence of up to ten per million, is the most severe cutaneous extraintestinal manifestation seen in inflammatory bowel diseases, and it is more frequent in women than men up to 76% of cases [5][6][7].Lesions are often diagnosed as non-healing ulcers and patients undergo debridement, which can lead to catastrophic deterioration through hyper pathergy response and affects lower limbs, usually ulcerative type.
Approximately 85% of cases are ulcerative type, other subtypes also included: Bullous, Vegetative, Pustular, Peristomal, and Superficial granulomatous variants [8][9][10].The different subtypes sometimes change from one to another and remain a clinical difficult diagnosis, in addition is necessary to rule out other causes of skin ulcers such as arterial and venous diseases, hematological causes (sickle cell disease, cryoglobulinemia and antiphospholipid syndrome), vascular occlusion, vasculitis, infections, calciphylaxis, drug-induced ulcers, primary or metastatic tumors, and Martorell ulcer [11].PG diagnosis is based on the pattern recognition of the skin lesions.
In our case, the diagnostic difficulty came because skin involvement began long before enteric manifestations, this onset is not commonly reported in reviewed bibliography [12], evidencing deficiencies to establish a link as dermopathies of systemic origin, "putting the cart before the horse", with diagnostic delay, worsen the outcome, and affecting the quality of life of the patient.However, all the roads led to Rome.Pyoderma gangrenosum is a diagnosis of exclusion both clinically and histologically, without specific histologic features  or lab markers criteria that aid in its diagnosis [13][14][15]; is a disease of young people, reviewed literature agreed between 15 and 40 old years on average [1,4].Being a woman is another element to consider, vast majority of cases reported are female [16,17].
Current chronically ill patient, previously healthy with skin manifestations that cannot be explained by common causes such as infection by fungi, bacteria's, parasites, HIV, and not proved focus of sepsis, with a noticeable increase in inflammatory response markers such as erythrocyte sedimentation rate and C-reactive protein; a disease of immune origin as part of our differential diagnosis should be considered.Despite gastro-intestinal manifestations started months after the skin lesions, they were vague and not symptomatically relevant to the patient, they cannot be underestimated, because approximately 50 percent of patients with PG have another related disorder, such as ulcerative colitis, Crohn's disease, or rheumatoid arthritis [18].IBD is the most common systemic illness associated and the rate is approximately 30%.UC increases the odds of developing PG by 15-fold, with the highest probability of developing PG occurring within the first year after the diagnosis of UC [19,20], colonoscopy or proctosigmoidoscopy with biopsy are the tests of choice for diagnosis.Thornton and cols found UC colitis in six patients over 14 patients with PG [21].In our case, colonoscopy was performed, and macroscopic examination described the existence of ulcerative colitis, pathology study reported unspecific colitis.Tests such as perinuclear antineutrophilic cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies are promising, but not yet recommended for routine use.Maverakis et al. created a Delphi consensus, which suggests that further investigation could be done, only if we have a neutrophilic infiltrate histology, and Jockenhöfer et al. developed the PARACELSUS score based on the prevalence of several features typically found in PG [22,23].Despite these efforts, early diagnosis is still difficult and, so far, no proposal has been validated [24].Nevertheless, our patient satisfied all the above diagnosis criteria.PG can follow a course independent to that of the bowel disease, however, most reported cases describe PG occurring in patients with an established diagnosis of IBD but is not closely related to the activity of UC, can also manifest during periods of bowel disease quiescence.

Treatment
In general, the therapeutic approach is determined by the severity of the symptoms and the degree of colonic involvement.Approximately 66 percent of patients will achieve clinical remission with medical therapy, and 80 percent of treatment-compliant patients maintain remission.If present, the underlying systemic disease must be treated, but there is no accepted correlation between the underlying systemic disease severity and the severity of pyoderma gangrenosum [25].Our management included: Gentle local wound and dressings, pain control, intravenous steroids (Hydrocortisone 100 mg IV q 6 hrs), additionally sulfasalazine (50 mg/kg/day).Remission of skin lesions was spectacular (Figure 5), as well as the fading of colonic manifestations after two weeks of treatment.Other alternatives like cyclosporin, mycophenolate mofetil, anti-TNF, intravenous immunoglobulins, interleukin 1 antagonists, and ustekinumab are available, but were not necessary in this case.

Conclusions
It is necessary to emphasize that despite the typicality of the lesions in PG, it is considered a rare entity worldwide with estimated prevalence of two to three cases per 100,000 people and an adjusted incidence rate of 0.63 per 100,000 person-years.So far is less common in sub-Saharan Africa, where only few cases are documented [25,26].This being the first case reported in The Gambia, so it is necessary to draw the attention of general practitioners, especially the youngest in our subregion.Another clinical challenge in this patient is the fact that skin lesions came before manifestations of intestinal diseases, and considering the high association with systemic diseases, it is imperative until proven otherwise to rule them out intensively.

Figure 1 .
Figure 1.Large ulcer on the front side of the right leg.

Figure 2 .Figure 3 .
Figure 2. Large ulcer on the right knee

Figure 5 .
Figure 5. Comparsion before and after treatment