The co-occurring immune-mediated diseases include acute rheumatic fever, vasculitis, and immune thrombocytopenic purpura (ITP).

Acute rheumatic fever is an immune mediated disease that can follow a GAS infection along with PSGN. However, the epidemiology and immunology of the two diseases are different, and co-occurrence of the two diseases in the same patient is rare [9]. Gibney et al. first reported a case with simultaneous acute rheumatic fever and biopsy-proven PSGN [10]. Since then 17 patients with co-occurrent acute rheumatic fever and PSGN have been reported [11]. It is not clear why simultaneous PSGN and acute rheumatic fever are rare. One explanation may be that only about 15 of the more than 80 known M serotypes of GAS have both nephritogenic and rheumatogenic antigenic features [9].

Vasculitis is not a frequent disorder correlated with GAS infection. However there have been several articles of HSP [6] or Henoch-Schönlein purpura with nephritis (HSPN) [7]. Despite the complete pathogenic part of GAS infection that devotes to the evolution of vasculitis is not clear, an immune complex-mediated mechanism caused by GAS infection has been speculated [12].

Childhood ITP, an autoimmune disease with antibodies detectable against platelet surface antigens, often occurs after a viral infection, such as influenza, Epstein-Barr, varicella zoster, rubella virus [13] but may also be preceded by a bacterial infection [14]. Since the first reported ITP cases in two patients with PSGN [15], several cases of thrombocytopenia in patients with PSGN have also been reported [13,14]. Muguruma et al. postulated about the pathogenesis of correlated diseases based on development of antibodies that were cross-response against GAS and platelets [14].

Non-immune-mediated conditions of PSGN include posterior reversible encephalopathy syndrome (PRES) and thrombotic microangiopathy.

Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a recently-described brain disorder with typical radiological findings of bilateral gray and white matter abnormalities in the posterior regions of the cerebral hemispheres and cerebellum [16,17]. The clinical symptoms include headache; decreased alertness; mental abnormalities such as confusion and diminished spontaneity of speech; behavior changes that range from drowsiness to stupor, seizures, vomiting; and visual perception abnormalities, such as cortical blindness [18]. The causes of PRES can vary, but it is commonly attributed to acute increase in blood pressure, renal failure, fluid retention, and treatment with immunosuppressive drugs [17]. Although the pathophysiology of PRES is not completely understood, it is believed that severe hypertension or other causes of PRES induce breakdown in cerebral autoregulation, which leads to leakage of fluid into the brain parenchyma. The leakage of fluid into the brain parenchyma is detected as vasogenic edema on neuroimaging studies [19]. The prognosis of PRES is generally benign, but delay in diagnosis and treatment can result in permanent sequelae to the affected brain tissues [17].

Thrombotic microangiopathy (TMA) is a pathological process that involves thrombocytopenia, microangiopathic hemolytic anemia, and microvascular occlusion. TMA is common in hemolytic uremic syndrome (HUS) associated with shiga toxin or invasive pneumococcal infection, atypical HUS (aHUS), thrombotic thrombocytopenic purpura (TTP), and other disorders including malignant hypertension [20]. Histologic features of TMA include vessel wall swelling, thickening and separation of the endothelial cell from the basement membrane, aggregation of substance in the subendothelial space, intraluminal platelet thrombosis, partial or complete vascular luminal occlusion, and red blood cell fragmentation [21].

There have been at least 10 cases describing TMA associated with PSGN [22-24]. All patients exhibited hypertension, and renal replacement therapy was performed in 3 patients. Renal pathology revealed the appearance of both PSGN and TMA in 3 patients and showed PSGN features without characteristics of TMA in 7 patients. The outcome in all patients was good.

Although the precise pathogenesis of TMA in patients with PSGN is not clear, 2 causes have been speculated: serious hypertension and streptococcal neuraminidase [22,23]. HUS has been reported as a consequence of severe hypertension, regardless of the cause. If severe hypertension is temporary, histological features of TMA are not present. But hypertension becomes malignant, pathologic lesions show characteristics of TMA [22]. Another available explanation of TMA in PSGN is adjustment of vascular endothelial cells by streptococcal neuraminidase. Circulating neuraminidase triggers antigen-antibody interaction and may injure the vascular endothelial cells, leading to the clinical manifestations of HUS [23].

Atypical clinical manifestations or courses of PSGN are acute nephritis without definite urinary abnormalities and relapse of the illness.

Patients with PSGN usually show hematuria and proteinuria. But there are several reports of histologically proven PSGN patients with minimal or no urinary abnormalities [25-27]. Most patients showed edema and hypertension, and some of them exhibited pulmonary congestion or edema. All patients improved completely without any residue. The reasons for the normal or minimal urinary abnormalities during the course of PSGN is not clear [26,27].

Recurrence of PSGN is a rare occurrence, probably because of the relatively limited number of nephritogenic strains of streptococci and the acquirement of protective immunity against a nephritogenic streptococcal antigen after an initial episode of PSGN [28]. Although incidences of recurrent PSGN have been reported to range from 0.7% to 7.0% in several clinical studies, and a few cases of recurrent PSGN have been reported [28-30], the exact pathophysiological mechanisms that cause recurrence of PSGN remain unclear [28]. Relapse of PSGN in some patients probably caused by defect of a natural immune response against nephritogenic streptococcal components such as NAPlr [28]. Recently, a patient with selective IgA deficiency exhibited two episodes of PSGN [30]. It might suggest that a failure of IgA defenses may also lead to streptococcal re-infection and cause recurrent PSGN. Because unusual or atypical features of PSGN can lead to diagnostic delays or misdiagnosis of the disease, early perception is important to ensure that the patient receives acceptable treatment.